Autonomic Regulation of Penile Erection
Summary and Keywords
Penile erection is a part of the human male sexual response, involving desire, excitation (erection), orgasm (ejaculation), and resolution, and autonomic nerves are involved in all phases. Autonomic innervation of smooth-muscle cells of the erectile tissue is provided by the cavernous nerve. Motor and sensory innervation is derived from the pudendal nerves and their terminal branches, that is, the dorsal nerves of the penis, which carry impulses from receptors harbored in the penile skin, prepuce, and glans. Erection begins with an increased flow in the pudendal arteries and dilatation of the cavernous arteries and helicine arterioles in association with relaxation of the smooth muscles of the trabecular network, causing engorgement of blood in the corpora. This leads to compression of subtunical venules by the resistant tunica albuginea and erection. During detumescence these events are reversed.
Our current understanding of penile erection as a complex physiologic process that occurs through a cascade of neurologic, vascular, and humoral events has gone through a long evolutionary process (see, e.g., Van Driel, 2015). Penile erection is a part of the human male sexual response, involving desire, excitation (erection), orgasm (ejaculation), and resolution, and autonomic nerves are involved in all phases. Penile erection is basically a spinal reflex controlled by a complex and coordinated interplay of multiple systems involving the brain, spinal cord, and relevant peripheral organs. Details of the different phases of the sexual response have been described in numerous reviews (Alwaal, Breyer, & Lue, 2015; Andersson, 2001, 2011; Andersson & Wagner, 1995; Argiolas & Melis, 2005; Clement & Giuliano, 2016; Dean & Lue, 2005; Giuliano & Clement, 2005; Giuliano, Rampin, Benoit, & Jardin, 1995; Hsieh et al., 2012). A brief review is given below on the autonomically innervated structures of the male genital tract and their roles in the generation of an erectile response. Much of our knowledge is derived from studies performed in animals. However, when possible, this presentation is focused on human functions in vivo and in vitro.
Corpora cavernosa and corpus spongiosum
The human penis consists of three corpora, which are cylindrical spongy bodies containing erectile tissue (Andersson & Wagner, 1995; Clement & Giuliano, 2015; Hsieh et al., 2012; Hsu et al., 2004; Wagner, 1981a). The paired corpora cavernosa are placed dorsally, and the corpus spongiosum surrounds the distal segment of the urethra (penile urethra) on the ventral side of the penis (Figure 1). Proximally, the corpora cavernosa divide bilaterally to form the roots of the penis (penile crura), which attach to the perineum via the ischiopubic ramus. Distally, the corpus spongiosum expands and covers the distal part of the corpora cavernosa to form the penile glans. Corpora cavernosa and corpus spongiosum share common histologic features that consist of sinuses (trabeculae, cavernae) lined by endothelium and separated by connective tissue septa deriving from the tunica albuginea. The cavernous bodies share a perforated septum, incomplete in the human, which allows them to function as a single unit.
The tunica albuginea is a multilayered structure of inner circular and outer longitudinal layers of connective tissue, enveloping the corpora cavernosa (Hsu, Brock, Martínez-Piñeiro, et al., 1994). The tunica albuginea has unique biomechanic properties and is composed of fibrillar collagen interlaced with elastin fibers. It affords great flexibility and rigidity when stretched, as well as providing tissue strength to the penis. The inner coat contains the cavernosal erectile tissue and supports it by radiating throughout the cavernosum bodies (Hsu, Brock, von Heyden, et al., 1994). The outer coat extends from the penile glans to the proximal crura and provides strength to the tunica albuginea. Deep (Buck’s) and superficial (Colle’s) fasciae envelop the tunica albuginea and enclose penile blood vessels and nerves. The penile skin is continuous with that of the abdominal wall and covers the glans of the penis as the prepuce to reattach at the coronal sulcus. The skin of the penile shaft has no hair follicle, eccrine sweat, or sebaceous glands, except at the base of the glans corona, where smegma is produced.
Striated Muscles Participating in Erection
The striated perineal ischiocavernosus and bulbospongiosus muscles have an important role in the male sexual response (Hsu et al., 2004; Schmidt & Schmidt, 1993). These muscles receive sensory as well as autonomic sympathetic neurons (Botti et al., 2012). The ischiocavernosus muscles attach to the ischial tuberosities and ischiopubic rami of the pubic bone and partially cover the penile crurae. The main function of the ischiocavernosus muscles is to provide extra rigidity of the erected penis by compressing the penile crus during the rigid phase of erection. The major function of the bulbospongiosus muscle is to act as a pump that forcefully propels sperm out of the body from the prostatic urethra to the urethral meatus during the expulsion phase of ejaculation.
Many theories of what causes penile erection have been suggested over the centuries (see van Driel, 2015). Hippocrates stated that erections were generated by pneuma and vital spirits flowing into the penis. Discarding previous theories, Leonardo da Vinci, based on his own observations at a public hanging and at the subsequent dissection of the body, realized the importance of penile blood flow (van Driel, 2015).
There are three paired main arteries in the penis (Figure 2). Penile arteries show high interindividual variability in branching, courses, and anastomoses (Bare, DeFranzo, & Jarow, 1994). The main blood supply to the penis is provided by the internal pudendal artery (Andersson & Wagner, 1995; Clement & Giuliano, 2015; Yiee & Baskin, 2010), but the erectile tissue can also receive blood supply via the accessory internal pudendal arteries (Droupy, Giuliano, Jardin, & Benôit, 1999; Droupy et al., 1999). After giving off the perineal artery in Alcock’s canal, the internal pudendal artery becomes the penile artery and then terminates in three branches: bulbourethral, cavernous, and deep dorsal penile arteries.
The bulbourethral arteries vascularize the urethra, corpus spongiosum, and glans (Diallo et al., 2013). After penetration of the tunica albuginea, the cavernous artery (deep penile artery) enters the crura of the corpora cavernosa. It is accompanied by the cavernous veins and the cavernous nerves, and divides into multiple branches, the corkscrew-shaped, muscular helicinal arteries (150–350 μm in diameter). These are the penile resistance vessels and open directly into the cavernous lacunae (Király et al., 2013; Simonsen, García-Sacristán, & Prieto, 2002; Simonsen et al., 1997). They receive a rich adrenergic innervation (Andersson, Hedlund, & Alm, 2000; Böck & Gorgas, 1977). The (deep) dorsal artery, which runs distally beneath Buck’s fascia together with the (deep) dorsal vein and the paired dorsal nerves, is responsible for enlargement of the glans penis during erection.
The fascia and skin of the penis receive blood from both the deep dorsal artery and the external pudendal arteries. The urethral artery runs longitudinally through the corpus spongiosum lateral to the urethra and supplies not only corpus spongiosum but also glans penis and urethral tissue. The bulbar artery provides blood supply to Cowper’s glands and the proximal urethral bulb. Arteriovenous shunts have been demonstrated at all levels of arterial branching (Droupy et al., 1999) and can be found outside as well as inside the tunica albuginea.
Banya et al. (1989), using scanning electronic microscopy of vascular corrosion casts, suggested that there are two circulatory routes in the human corpora, one connecting the cavernous artery to capillary networks collected into the venular plexus just beneath the tunica albuginea. This was suggested to serve as a main circulatory pathway during the flaccid state, with the capillaries functioning as nutritional vessels. The other route is through anastomoses from the cavernous artery, via the helicine arteries to the cavernae, which are then emptied into the post-cavernous venules. Benoit et al. (1999) found transalbugineal anastomoses between the cavernous artery and the spongiosal arterial network, and demonstrated two venous pathways, one in the pelvis and one in the perineum, with a common origin from the deep dorsal penile vein. They concluded that the two neurovascular pathways destined for the penis are topographically distinct, one located in the pelvis and the other in the perineum, and that they are both involved in penile erection. The sequence of their involvement in the phases of erection and detumescence have not been clarified.
The venous system of the human penis has been widely studied (Hsu et al., 2003). There are three sets of veins draining the penis: the superficial, intermediate, and deep dorsal veins (Yiee & Baskin, 2010). The deep venous system drains both the corpora cavernosa and the corpus spongiosum (Hsu et al., 2003). The post-cavernous venules coalesce to form larger emissary veins that traverse obliquely through the tunica albuginea, allowing them to be compressed during erections for penile tumescence. The emissary veins of the middle and distal penis join to form the circumflex veins, which empty into the deep dorsal vein. Both the emissary and circumflex veins have valves. A deep set of bulbar and urethral veins drains the corpus spongiosum. The intermediate set of veins is deep to Buck’s fascia, but superficial to the tunica albuginea. Veins from the glans penis form a retrocoronal plexus that drains into the deep dorsal vein, as do a series of emissary and circumflex veins from the corpora cavernosa. The deep dorsal vein courses proximally in the midline between the two corpora cavernosa and empties into the preprostatic venous (Santorini’s) plexus (Hsu et al., 2003). The superficial dorsal vein drains the skin and the subcutaneous tissue superficial to Buck’s fascia. It drains into the superficial external pudendal vein.
Innervation and Transmitters
According to van Driel (2015), Albrecht von Haller, living in Switzerland during the 18th century, was the first who explained penile erection as an increase of blood flow under control of the nervous system.
Penile innervation consists of the cavernosal, perineal, and dorsal nerves. The cavernous trabecular smooth muscle and penile vasculature receive nerves containing adrenergic, cholinergic and non-adrenergic, non-cholinergic transmitters, which work to regulate penile erection and detumescence (Andersson et al., 2000; Andersson & Wagner, 1995; Dean & Lue, 2005; Hedlund, Ny, Alm, & Andersson, 2000; Simonsen et al., 2002).
This is managed through a balance between contraction and relaxation factors that determines the functional state of the penis (Andersson, 2001). Pro-erectile fibers are provided by the cavernous nerves. These nerves are an extension of the efferent autonomic fibers of the pelvic plexus extending toward the corpora cavernosa. In the pelvis, they are located within neurovascular bundles, which are in contact with the prostate and pass through the urogenital diaphragm in contact with the urethra. The neurovascular bundles can be damaged during radical prostatectomy, leading to erectile dysfunction (Walsh & Donker, 1982, 2017).
The anti-erectile sympathetic preganglionic efferent nerves originate in the intermediolateral nuclei of the thoracolumbar segments (T11–L1) of the spinal cord and synapse in the abdominopelvic (lumbosacral) paravertebral sympathetic chain, from where the noradrenergic postganglionic nerves join the sacral nerves and reach the penis via the pudendal nerve. Activity in adrenergic nerves causes detumescence of the erect penis, and sympathetic tone also maintains the penis in the flaccid state (see “Hemodynamics of Erection and Detumescence”).
In addition to this efferent autonomic (visceromotor) nervous system emerging from the pelvic plexus, there is an afferent somatic (sensory) system (Diallo et al., 2013). Sensory innervation is provided by the pudendal nerves and their terminal branches, that is, the dorsal nerves of the penis that travel within Buck’s fascia, together with the dorsal arteries and veins (Yiee & Baskin, 2010). Impulses from sensory receptors in the penile skin, prepuce, and glans are carried by the dorsal nerve of the penis to the upper sacral segments (S2–S4) of the spinal cord from. This is the principal somatic sensory route for the penis (Chapelle, Durand, & Lacert, 1980), but it is also involved in reflex ejaculations in response to massage or vibration of the glans penis among patients with spinal cord injuries (Everaert et al., 2010).
Parasympathetic Pathways and Transmitters
Eckhard (1863) elicited penile erections in dogs by stimulation of nerves or plexus on the rostromedial surface of the levator ani muscle, and found that during the tumescence phase, the effluence of blood from engorged erectile tissue and the dorsal vein was about 8–15 times greater than in the flaccid state. His findings, which later have been confirmed by many investigators in various species (Andersson & Wagner, 1995), have led to the commonly accepted view that the sacral parasympathetic pathways in the pelvic nerves are the primary efferent system for generating penile erection.
In humans, the cells of origin for preganglionic neurons involved in the parasympathetic efferent activity of the penis are located in the intermediate gray matter of the second to fourth sacral spinal cord segments. Together with axons from other spinal centers, these neurons form the sacral efferent fibers emerging in the anterior roots. Electrical stimulation of the roots S1–S4 causes erection in humans. The main source of erectogenic fibers seems to be S2, with contributions coming from either S3 or S4 (Brindley, Polkey, Rushton, & Cardozo, 1986). The sacral preganglionic nerves travel to the pelvic plexus in the pelvic nerves (nervi erigentes), which form three to six distinct trunks in humans (Learmonth, 1932). Fibers from the inferior hypogastric nerves join the pelvic nerves to form the pelvic plexus. The morphological, neurochemical, and electrophysiological properties of the pelvic ganglion cells vary among species—in humans, the pelvic plexus is occasionally referred to as the inferior hypogastric plexus and lies in the pelvic fascia on either side of the lower genitourinary tract and rectum (Walsh & Donker, 1982, 2017).
The pelvic plexus plays a major role in the neural regulation of urogenital function and serves as a relay and integration center within which preganglionic axons make synaptic connections with postganglionic neurons innervating the penis. Numerous detailed studies of the pelvic ganglion pathways to the penis have been performed in the rat (see Andersson & Wagner, 1995). Neurons innervating the penis have been shown to be located in one portion of the major pelvic ganglion, a structure that corresponds to the pelvic plexus in other species. It is not known whether individual penile postganglionic neurons receive excitatory inputs from both sympathetic and parasympathetic pathways at the level of the pelvic ganglia; however, such convergent inputs have been demonstrated in pelvic ganglia of the cat, but not the rat. In humans, the autonomic nerve fibers projecting to the penis from the pelvic plexus—the cavernous nerves—run between the prostatic capsule and the endopelvic fascia, then travel along the posterolateral aspect of the prostate until the prostatic apex, where they are only a few millimeters from the urethral lumen. Distal to the membranous urethra, some fibers penetrate the tunica albuginea of the corpus spongiosum, and the remaining fibers, lying at the 1 and 11 o’clock positions, enter the penile crura along with terminal branches of the pudendal artery and cavernous veins. The course of the cavernous nerves is clinically important because bulbous or membranous urethral injury, as well as prostatic, rectal, or bladder surgery, can disrupt the nerves and may result in impairment of erectile function (Walsh & Donker, 1982, 2017). Parasympathetic neural activity induces vasodilatation in the penile blood vessels and increases blood flow to the cavernous tissue.
Transmitters and Mediators
The dense cholinergic innervation of the human corpus cavernosum and corpus spongiosum contains numerous transmitters and mediators (Everaert et al., 2010; Hedlund et al., 2000). The main relaxant transmitter is generally considered to be nitric oxide (NO) generated from neuronal NO synthase (nNOS) containing nerves, but the contributions of other relaxant transmitters have never been established. Along strands of smooth muscle, rich numbers of vesicular acetylcholine transporter (VAChT)-, nNOS-, vasoactive intestinal polypeptide (VIP)-, tyrosine hydroxylase (TH)-, and very few heme oxygenase-1 (HO-1)-immunoreactive (-IR) nerve fibers were observed. Immunoreactivities for VAChT/nNOS, VAChT/VIP, and nNOS/VIP were generally found in the same varicose nerve terminals. VAChT, NOS, and VIP were found in the same nerve terminals within the human corpus cavernosum and corpus spongiosum, suggesting that these nerves comprise a distinct population of parasympathetic, cholinergic nerves. TH-IR nerve fibers or terminals did not contain immunoreactivities for VAChT, NOS, or VIP.
In the endothelium lining penile arteries, immunoreactivities for eNOS, HO-1, and HO-2 have been detected (Hedlund et al., 2000). Single endothelial cells, lining the sinusoidal walls of the corpus cavernosum and corpus spongiosum, were found also to contain eNOS and HO-immunoreactivities (Hedlund et al., 2000). Blood flow mediated (shear-stress) release of NO in penile vessels has been demonstrated (Simonsen et al., 2002; Wessells et al., 2006). Thus, NOS and heme oxygenases can be demonstrated not only in nerves but also in endothelium, and endothelially derived NO and carbon monoxide (CO) may have a complementary role in penile erection (Yetik-Anacak, Sorrentino, Linder, & Murat, 2015). This may also be the case for a third gaseous transmitter, hydrogen sulphide (H2S). The enzymes generating H2S, cystathionine β-synthase and cystathionine γ-lyase, are present in human penile erectile tissue (d’Emmanuele et al., 2009) and localized within muscular trabeculae and the smooth-muscle component of the deep penile artery. However, the role of H2S in human penile erection remains to be established (Mostafa et al., 2018; Srilatha, Adaikan, Li, & Moore, 2007; Yetik-Anacak et al., 2015).
Sympathetic Pathways and Transmitters
The sympathetic innervation of the penis and pelvic floor is shown in Figure 3. The sympathetic preganglionic nerve fibers to the penis generally arise from neurons in intermediolateral gray matter of the lower thoracic (T10) and upper lumbar (L3) spinal cord segments, the segmental levels showing species variation (Andersson et al., 2000). Thus the segmental origin in humans most often is from T11 to L2; T10 to T12; and in, for example, dog T12–L3 (de Groat & Booth, 1993). Preganglionic fibers leave the cord via the ventral roots of the corresponding spinal nerves, then pass via the white rami communicantes to the paravertebral sympathetic chain ganglia, making synaptic connections with ganglion cells at various levels. The chain ganglion cells projecting to the penis are located in the sacral and caudal lumbar ganglia. Via the gray rami, the postganglionic axons reach the urogenital tract through the pelvic, cavernous, and pudendal nerves. Preganglionic fibers may also leave the chain ganglia and pass along the lumbar splanchnic nerves to prevertebra1 ganglia in the superior hypogastric plexus (presacral nerve), which in humans lies on the great vessels at the level of the third lumbar to first sacral vertebrae. Stimulation of this plexus in humans can cause either erection or penile shrinkage. The superior hypogastric plexus divides into the left and right hypogastric nerves as the sympathetic fibers extend caudally toward the pelvic plexus. The hypogastric nerves contain postganglionic fibers from prevertebra1 ganglion cells, as well as preganglionic axons that pass through the prevertebral ganglia to make synaptic connections in the pelvic plexus, which is an important integrator site for the penile autonomic innervation. Sympathetic postganglionic axons originating in the pelvic plexus, as well as in paravertebral and prevertebral ganglia, travel to the penis as the cavernous nerve, and possibly as other, smaller nerves, which follow the blood vessels.
Inhibitory nerves containing nonadrenergic noncholinergic (NANC) transmitters reaches the penile smooth muscle via the pelvic and hypogastric nerves. Thus, the sympathetic pathways to the penis may mediate anti-erectile (noradrenaline) as well as erectile (NANC transmitters) effects (Andersson et al., 2000; Andersson & Wagner, 1995).
Transmitters and Mediators
The nerve populations in the penis have been categorized according to transmitter content as adrenergic, cholinergic, and NANC nerves. All these types of nerve may contain more than one type of transmitter/mediator (Andersson, 2001, 2011; Andersson & Wagner, 1995). Thus, NANC nerves can contain neuropeptides but also other transmitters and transmitter/modulator generating enzymes, such as NOS and HO. NANC transmitters/modulators can also be found in both adrenergic and cholinergic nerves. The numerous agents demonstrated or assumed to be causing or to contribute to penile erection have been discussed in detail in previous reviews (Andersson, 2001, 2011; Andersson & Wagner, 1995).
A large fraction of the nerves supplying trabecular smooth muscle are adrenergic, as indicated by positive immunoreactivity of tyrosine. Particularly around the helicine arteries, a rich adrenergic innervation can be found (Andersson et al., 2000), underlining the importance of noradrenaline in the control of these vessels. Jen, Dixon, Gearhart, and Gosling (1996) reported that nNOS and TH were colocalized in nerves supplying the postnatal human penis. nNOS can also be found in TH-containing nerves in the adult human penis (Tamura et al., 1995), suggesting that NO may be generated by adrenergic nerves. Whether this really is the case has not been definitely established. Hedlund, Alm, and Andersson (1999) showed that in the rat penis, nNOS- and TH-IRs, VAChT vesicular and TH-IRs, or VIP and TH-IRs were found in separate nerve fibers and terminals. Similar results were found in the human corpus cavernosum. Further supporting the view that TH and nNOS are not colocalized, chemical sympathectomy by 6-OH dopamine was found to abolish TH-IR nerve structures in the rat and mouse corpus cavernosum. However, the amount and distribution of nerves containing immunoreactivities for NOS, VAChT, and VIP were unaffected. The distributions of nNOS-VAChT-VIP-IR and TH-IR nerves were found close together in similar patterns, which should make possible cholinergic modulation of the release of noradrenaline from adrenergic nerves.
Thus, available evidence favors the view that nNOS and TH are localized to separate nerve populations. Noradrenaline and neuropeptide Y (NPY) are often co-localized and may act in synergy (Lundberg, Modin, & Malmström, 1996). This is also the case in the penis, where chemical sympathectomy using 6-OHDA abolished NPY immunoreactivity (Andersson et al., 2000). NPY has been demonstrated in penile vasculature and erectile tissue in several species including humans, monkey, rabbit, guinea pig, and rat (Andersson & Wagner, 1995). Moderately high concentrations of NPY were found in the human corpus cavernosum, and it was suggested that NPY could be intimately involved in the control of erection (Adrian et al., 1984). Wespes et al. (1988) found a concentration of NPY containing nerve fibers in the inner part of the adventitia close to the media of the arterial and venous vessels, and among the trabecular smooth muscle cells of the human penis. They speculated that NPY could act as a neurotransmitter or neuromodulator, especially during detumescence. Supporting this view, Giuliano et al. (1993) postulated that NPY co-localized with NA exerted a contractile effect on penile veins and could take part in detumescence. However, experimental evidence for this is still lacking.
Crowe, Burnstock, Dickinson, and Pryor (1991) found that the media of the deep dorsal vein of the human penis contained numerous NPY-IR nerves. If NPY has an enhancing effect on the vasoconstriction caused by noradrenaline, this may contribute to the venous occlusion necessary for obtaining an erection. Prieto et al. (2004) found in horse small penile arteries that NPY-IR nerves were widely distributed in the erectile tissues, with a particularly high density around helicinal arteries. They demonstrated that NPY can elicit dual contractile/relaxing responses through a heterogeneous population of postjunctional NPY receptors.
Somatic (Motor and Sensory) Pathways
Penile innervation involves visceromotor pathways for erection and somatic pathways for sensitivity (Diallo et al., 2013). The afferent somatic (sensory) system arises from the pudendal nerves (Tajkarimi & Burnett, 2011). These pudendal nerves follow a perineal route and ultimately become the dorsal nerves of the penis. The pudendal nerve is composed of efferent fibers innervating the ischiocavernosus, bulbocavernosus, and other striated muscles in the pelvis and perineum, but it also carries afferent information from various penile structures.
This is the principal somatic sensory route for the penis, supplying the outer layers, the foreskin, and the glans penis.
In humans, the pudendal motor neurons reside in Onuf’s nucleus in the second, third, and fourth segments of the sacral cord. The pudendal nerve leaves the pelvis through the lower part of the greater sciatic foramen, then travels through the lesser sciatic foramen to enter the pudendal (Alcock’s) canal within the obturator internus muscle. It gives off the inferior rectal nerve, then divides into the perineal nerve and the dorsal nerves of the penis. The perineal nerve has muscular branches that supply the perineal muscles, the urethral sphincter, and part of the external sphincter, and a branch that supplies the corpus spongiosum.
The dorsal nerve of the penis forms the afferent pathway for reflex erection, and the nerve carries impulses to the spinal cord from the penile skin, prepuce, frenulum, glans, and the connective tissue septa of the corpus cavernosum (Andersson & Wagner, 1995, Diallo et al., 2013). In the human glans penis, the most numerous afferent terminations were found to be free nerve endings, but also corpuscular receptors can be demonstrated. The ratio of free nerve endings to corpuscular receptors was 10:1. The free nerve endings were derived from thin myelinated axons (Aδ) or from unmyelinated C-fibers. This sensory innervation makes the glans penis unique and unlike any other cutaneous area of the human body. In humans, branches of the cavernous nerve may travel in the vicinity of the dorsal nerve of the penis, and efferent projections from the pelvic plexus therefore cannot be excluded. The physiological significance of these efferent pathways is uncertain; it is possible that they control blood vessels within the penile skin or possibly modulate the sensitivity of cutaneous sensory receptors, as shown in dogs (Johnson & Kitchell, 1987). It is generally accepted that the pudendal nerve is the sensory pathway from the penis and that elimination of this input blocks reflexogenic erections evoked by manipulation of the penis.
Animal studies have suggested that the bulbocavernosus and ischicavernosus muscles are involved in the mechanisms leading to penile erection and sexual activity (Schmidt & Schmidt, 1993). Local anesthesia of the nerves to these muscles was shown to greatly reduce the intracavernous pressure increase shown to occur in different species during coitus. In humans, the functional significance of the somatomotor system in erection is unclear. Some patients with lesions of the spinal cord and lacking sacral reflexes were found to have maintained erections, which suggested to them that perineal muscles were not necessary for erection (Bors & Comarr, 1960), and erection may occur without electromyogram (EMG) activity in perineal muscles (Kollberg, Petersen, & Stener, 1962). Gerstenberg, Levin, and Wagner (1990) could demonstrate no EMG activity in the bulbo- and ischiocavernosus muscles during erection and detumescence cycles induced by visual sex stimulation. Lavoisier et al. (Lavoisier, Courtois, Barres, & Blanchard, 1986; Lavoisier et al., 1988; Lavoisier, Schmidt, & Aloui, 1992) suggested that while efferent autonomic pathways are important for penile tumescence, rigidity is facilitated by ischiocavernosus smooth muscle contractions, as marked elevations in intracorporeal pressures occur simultaneously with such contractions during artificially induced erections. Support for this view was obtained by Wespes et al. (1990), studying the effect of contraction of the bulbocavernosus muscles, voluntary or induced by dorsal nerve stimulation, on intracavernous pressure and erectile flow rates to induce and maintain an erection. Electrical stimulation of the cavernous nerve causes full erection, but without complete rigidity. It was speculated that rigid erection may be the result of contraction of the ischiocavernosus muscle, compressing the proximal ends of the corpora cavernosa. This will increase intracavernosal pressure above that of the systolic blood pressure and give greater rigidity to the penis. Tactile stimulation of the penis during sexual activity may trigger the “bulbocavernosus” reflex, which, during the initial vaginal intromission, may be of importance for a full intromission with maximal rigidity (Lavoisier et al., 1992).
Hemodynamics of Erection and Detumescence
There have been many controversies about the mechanisms of penile erection and its hemodynamics (Dean & Lue, 2005; Newman & Northup, 1981; Shirai et al., 1978; Van Driel, 2015). However, it has been well established that the time courses of event are different in the corpora cavernosa and corpus spongiosum.
1. In the flaccid state, the smooth muscle of the sinusoids and vessels are tonically contracted (Wagner, Gerstenberg, & Levin, 1989). Sexual stimulation triggers release of neurotransmitters from the cavernous nerve terminals and from vascular nerves, causing dilatation of the helicinal arteries and increased blood to the cavernae in both the diastolic and the systolic phases, and cavernous muscle relaxation. The increased flow in turn causes release of endothelial relaxant factors, enhancing smooth muscle relaxation.
2. The incoming blood is trapped by the expanding sinusoids. From flaccidity to erection, there was an eightfold mean increase of the intrapenile blood volume in human subjects (Shirai et al., 1976, 1978). Andersson, Bloom, and Mellander (1984) studied the erectile response evoked by pelvic nerve stimulation in the dog and found that erection in this species appeared to result from two main circulatory events. The first response was a prompt dilatation of the penile resistance vessels, causing a greatly increased arterial inflow, which in the early phase bypassed the cavernous bodies and therefore increased venous outflow to the same extent. This event has been confirmed by other investigators (Hanyu et al., 1992; Vardi & Siroky, 1990). The second response, characterized by a rapid filling of the corpora cavernosa and an increase in cavernosal pressure, was recorded after a distinct delay. This was attributed to a sudden opening of low-resistance “shunt vessels,” diverting part of the arterial inflow into the cavernous bodies. Vardi and Siroky (1990) suggested that the delay was due to relaxation of the smooth muscle of the cavernae and the time required to fill the now compliant cavernosal tissue with arterial blood.
3. Jünemann et al. (1989) suggested that this initial parasympathetic vascular mechanism was followed by the somatomotor muscular mechanism, producing penile rigidity by muscular compression of the blood-distended cavernous bodies through contraction of the ischiocavernosus muscles. This may be valid for the dog; however, a study in young normal volunteers showed that no electrical activity occurred in the ischio- or bulbocavernosus muscles during development of tumescence and erection unless the individual voluntarily contracted the muscles. Only during ejaculation did a well-defined electrical and contractile pattern occur (Gerstenberg et al., 1990).
4. The subtunical venular plexuses between the tunica albuginea and the peripheral sinusoids are compressed, reducing the venous outflow. Even if Shirai et al. (1978) stated that penile erection can occur without a venous-return blocking mechanism, several studies have directly demonstrated a restricted outflow during erection in humans (Aoki et al., 1986; Fournier, Jünemann, Lue, & Tanagho, 1987; Wagner & Uhrenholdt, 1980). This discrepancy can be explained by the recognition that the penis has two erectile systems: the high-pressure corpora cavernosa and the low-pressure corpus spongiosum and glans penis. This has been well documented in dogs (Carati, Creed, & Keogh, 1988; Creed, Karati, & Keogh, 1988; Jünemann et al., 1986), but also in humans (Banya et al., 1989).
5. The tunica albuginea is stretched to its capacity, which occludes the emissary veins between the inner circular and the outer longitudinal layers (Hsu et al., 2013). This further decreases the venous outflow.
6. The increased intracavernous pressure (around 100 mm Hg), raises the penis from the dependent position to the erect state (the full-erection phase). When the penis increases in volume by the accumulation of blood, an angle between 0 and 45 from the horizontal plane is created in the upright position. In this state, the shaft of the penis feels rigid, and the intracavernous pressure is close to the mean arterial blood pressure (Wagner, 1981b). In men with a long, heavy penis or a loose, suspensory ligament, the angle usually will not be greater than 90 degrees, even with full rigidity.
7. Contraction of the ischiocavernosus muscles may cause a further pressure increase (to several hundred mm Hg), resulting in the rigid-erection phase (Dean & Lue, 2005).
The hemodynamics of the corpus spongiosum and glans penis are somewhat different from the corpora cavernosa. In the dog, the dorsal penile veins drain only the glans penis and have no relation to the corpora cavernosa. During erection, the arterial flow increases in a similar manner; however, the pressure in the corpus spongiosum and glans is only one-third to one-half of that in the corpora cavernosa because the tunical covering (thin over the corpus spongiosum and virtually absent over the glans) ensures minimal venous occlusion. The venocclusive mechanism demonstrated in the corpora cavernosa was not found in the corpus spongiosum (Deysach, 1939; Purohit & Beckett, 1979). Thus, the corpora cavernosa may be a closed system, whereas the corpus spongiosum is a one-way flow system, draining freely through the penile veins. Therefore, spongiosal pressure is maintained primarily by a high-flow state through the glans penis, whereas cavernosal pressure depends on a venocclusive mechanism during erection (Vardi & Siroky, 1990).
During the full-erection phase, partial compression of the deep dorsal and circumflex veins between Buck’s fascia and the engorged corpora cavernosa contribute to tumescence of the glans, although the spongiosum and glans essentially function as a large arteriovenous shunt during this phase. In the rigid-erection phase, the ischiocavernosus and bulbocavernosus muscles forcefully compress the spongiosum and penile veins, which results in further engorgement and increased pressure in the glans and spongiosum (Dean & Lue, 2005).
The hemodynamic changes during detumescence represent a reversal of those occurring during erection: contraction of the cavernous smooth muscles, decrease of the arterial flow, and full restoration of venous outflow, either passively (owing to intrinsic smooth muscle tone) or actively (increased sympathetic activity), or both.
In dogs, where erection had been induced by cavernous nerve stimulation, Bosch et al. (1991) discriminated three phases of detumescence: an initial phase, exhibiting a small pressure increase; a second phase, showing a slow pressure decrease; and a third phase, in which a fast decrease occurred. During the initial phase, a small pressure increase could be recorded, which could be abolished by aortic clamping. This phase was considered to be dependent on arterial inflow and cavernous smooth muscle contraction. Increased activity in the sympathetic nervous system leads to increased tone in the helicine arteries and contraction of the trabecular smooth muscle.
The second phase was a period of slow pressure decrease; arterial blood flow had returned to normal; only limited venous drainage probably occurred during this phase, suggesting that the venocclusive mechanism was still activated. Sympathetic stimulation abolished this phase.
During the third phase, there was a fast decrease in intracavernous pressure. The venocclusive mechanism became inactivated; the venous drainage completely restored; and the penis returned to the flaccid state. Similar phases of detumescence have been described in humans (Andersson & Wagner, 1995).
In human volunteers, the electrical activity of the cavernous smooth muscle tissue, which has been shown to decrease during erection, resumed during detumescence (Wagner et al., 1989). There is a transition phase, where increased activity in the sympathetic nervous system leads to increased tone in the helicine arteries and contraction of the trabecular smooth muscle. Arterial flow is resumed at a low level, and the venocclusive mechanism is still activated. In the next phase, which is the initial detumescence phase, there is a moderate decline of intracavernous pressure, indicating a reopening of the venous outflow channels and a decreasing arterial flow. In a third phase, the fast detumescence phase, the intracavernous pressure declines rapidly; the venocclusive mechanism becomes inactivated; arterial flow decreases to its prestimulation level; and the penis returns to the flaccid state.
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