Plasma levels of cyclic guanosine-3′,5′-monophosphate in the cavernous and systemic blood of healthy males during different functional conditions of the penis

The relaxation of cavernous arterial and trabecular smooth muscle is dependent upon the stimulation of guanylyl cyclase activity by nitric oxide (NO), which is released from nerve terminals and endothelial cells within the cavernous tissue, and the subsequent accumulation of cyclic guanosine-3',5'-monophosphate (cGMP) in the intracellular space. The present study was undertaken to determine whether or not plasma levels of cGMP in the systemic and cavernous blood of healthy male subjects change from penile flaccidity to tumescence, rigidity and detumescence. Fifteen adult healthy males were exposed to visual and tactile erotic stimuli to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein in the respective penile stages, and cGMP was determined in plasma aliquots by means of a radioimmunoassay. Mean systemic and cavernous plasma levels of cGMP in the blood samples obtained from the healthy volunteers ranged from 1.2-1.7 pmol/ ml. cGMP levels in the systemic circulation and in the cavernous blood did not change during developing erection, rigidity and detumescence. No significant differences were found between cGMP plasma levels in the systemic and cavernous blood in the different penile stages. Our results may reflect the fact that the stimulation of NO production in healthy males during sexual arousal and developing penile erection either does not yield substantial quantities of cGMP or that the rate of cGMP-extrusion from cavernous smooth muscle cells into the extracellular space accounts only for a minor fraction of plasma cGMP. Moreover, basal levels of cGMP in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection may conceal any local release of cGMP that may occur within the penile erectile tissue. Thus, we conclude that the quantification of cGMP is of no use in the evaluation of the physiologic mechanisms of penile erection in vivo.     

Cavernous and systemic testosterone levels in different phases of human penile erection

OBJECTIVES: To examine changes in testosterone levels in the cavernous and peripheral blood during different phases of erection because, although the determination of systemic testosterone levels has been well established in the diagnostic workup of erectile dysfunction, the exact role of testosterone in adult male sexual function remains unclear. METHODS: Blood samples were drawn simultaneously from the corpus cavernosum and the cubital vein of 54 healthy and normally potent volunteers during four different stages of the cavernous erectile tissue (flaccidity, tumescence, rigidity, and detumescence). Penile erections were induced by audiovisual and tactile stimulation, and testosterone levels were determined by radioimmunoassay. RESULTS: The mean testosterone level in the corpus cavernosum plasma during the flaccid state was 2.9 +/- 1.2 ng/mL. During tumescence and rigidity, the testosterone levels in the cavernous blood significantly increased, to 4.3 +/- 1.3 ng/mL and 4. 4 +/- 1.4 ng/mL, respectively. During detumescence, the cavernous testosterone levels dropped to 3.5 +/- 1.4 ng/mL. The changes in the testosterone levels in the peripheral plasma were less pronounced. A significant increase was also found in the peripheral testosterone levels from flaccidity (4.1 +/- 1.1 ng/mL) to tumescence (4.4 +/- 1. 4 ng/mL). No further increase in testosterone occurred during the phase of rigidity. From rigidity to detumescence, the peripheral testosterone levels dropped to 4.1 +/- 1.2 ng/mL. CONCLUSIONS: Penile erection was found to be accompanied by a significant increase in cavernous and systemic testosterone plasma levels. The estimated difference between the systemic and cavernous testosterone levels during penile flaccidity, when blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone and the activity of testosterone receptors in the corpus cavernosum smooth musculature.     

Is there a significance of histamine in the control of the human male sexual response?

Although histamine has been suggested to be involved in the control of male sexual function, including the induction of penile erection, its role in the human corpus cavernosum penis is still poorly understood. The aim of our study was to evaluate the course of histamine plasma levels through different stages of sexual arousal in the systemic and cavernous blood of healthy male subjects. Thirty four (34) healthy men were exposed to erotic stimuli to elicit penile erection. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Blood was also collected in the post-ejaculatory period. Plasma levels of histamine (ng ml(-1)) were determined by means of a radioimmunoassay. Histamine slightly decreased in the cavernous blood when the penis became tumescent. During rigidity, histamine decreased further but remained unaltered in the phase of detumescence and after ejaculation. In the systemic circulation, no alterations were observed with the initiation or termination of penile erection, whereas a significant drop was registered following ejaculation. Results are not in favour of the hypothesis of an excitatory role of histamine in the control of penile erection. Nevertheless, the amine might mediate biological events during the post-ejaculatory period.     

Systemic and cavernous plasma levels of endothelin 1 in healthy males during different functional conditions of the penis

The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters might be involved in this process. Endothelin 1 (ET-1), a 21-amino-acid peptide with potent and long-lasting vasoconstrictor activity, may be one of the factors contributing to such control. The present study was undertaken to determine whether plasma levels of ET-1 changed during flaccidity, tumescence, rigidity, and detumescence. We determined plasma levels of ET-1 in the peripheral and cavernosal blood of 32 potent adult male volunteers, in whom penile tumescence and erection were elicited by exposure to visual and tactile erotic stimuli. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1 was quantified in plasma aliquots obtained from the blood samples. Using the organ bath technique, we evaluated the contractile effects of ET-1 and norepinephrine (NE) on isolated human corpus cavernosum musculature. No significant change in ET-1 levels was observed in the peripheral or cavernosal blood in the process of developing erection, rigidity, or detumescence. The mean plasma level of ET-1 was 0.2–0.7 fmol/ml. In the organ bath, ET-1 elicited concentration-dependent contractions of isolated human corpus cavernosum, which were much more pronounced than those evoked by the adrenergic agonist NE. Our data indicate that despite the in vitro efficacy of ET-1 in stimulating contractile activity in isolated human cavernous smooth muscle, the peptide may not be of ultimate importance for the mechanism of flaccidity and detumescence in healthy males. Nevertheless, the exact role of ETs in the control of penile smooth muscle tone remains to be established.     

Systemic and cavernous plasma levels of vasopressin in healthy males during different functional conditions of the penis

The role of the sympathetic adrenergic system in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic-noncholinergic transmitters are involved in this process. Arginine-vasopressin (AVP, ADH), a pituitary peptide hormone with potent vasoconstrictor activity, may be one of the factors contributing to such control. The present study was undertaken to determine whether or not plasma levels of AVP change during penile flaccidity, tumescence, rigidity, and detumescence. We determined the plasma levels of AVP in the systemic as well as the cavernous blood of 25 healthy adult male volunteers who were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and erection. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and AVP was quantified in plasma aliquots obtained from the whole blood samples. A marked decline in mean AVP plasma levels from 5.4+/-2.7 ng/l during flaccidity to 2.9+/-2.5 ng/l during rigidity was registered in the systemic blood of the subjects. No further decline was observed when the rigid penis became detumescent. In contrast, no alterations in AVP plasma levels were detected in the cavernous blood under the different penile conditions. The results from our study are contrary to the hypothesis of a local release and uptake of AVP in the cavernous compartment in the control of penile flaccidity and detumescence. Moreover, our findings are not in favour of AVP as an important mediator involved in adrenergic neurotransmission in the corpus cavernosum penis. Nevertheless, our data indicate that the decrease in systemic AVP levels in response to sexual arousal might be a prerequisite to facilitate penile tumescence and rigidity in healthy males.     

降钙素基因相关肽在阴茎勃起机制中的作用

通过实验动物（成年雄性狗）研究肽能神经介质──降钙素基因相关肽（ＣＧＲＰ）在勃起机制中的作用。取动物海绵体平滑肌、阴部内动脉、静脉等组织离体灌注并活体海绵体内注射ＣＧＲＰ，证实对离体组织具有舒张作用，以海绵体平滑肌最强。活体海绵体内注射观察动脉血流量增加，海绵体内压升高，阴茎明显胀大。刺激海绵体神经诱导阴茎勃起检测ＣＧＲＰ水平变化，发现在勃起高峰时，海绵体组织内ＣＧＲＰ增高，面消退期血浆内ＣＧＲＰ升高。从而证实ＣＧＲＰ可导致海绵体平滑肌松弛、减少阻力，增快动脉血流，是促使阴茎勃起的主要神经介质之一。在消退期也可能参与使阻闭静脉的开放，加快回流的作用。     

Plasma levels of cavernous and systemic norepinephrine and epinephrine in men during different phases of penile erection

PURPOSE: Knowledge of the functional anatomy, hemodynamics, neurophysiology and pharmacology of penile erection has improved tremendously during the last 2 decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out up until now. Therefore, we conducted a study to examine plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in the peripheral and cavernous blood of healthy men during penile flaccidity and in different phases of erection. MATERIALS AND METHODS: Blood samples were drawn simultaneously from the corpus cavernosum (CC) and the cubital vein (P) in 53 healthy volunteers with normal erectile function, in four different functional states of the cavernous erectile tissue (flaccidity = 1, tumescence = 2, rigidity = 3, detumescence = 4). Penile erections were induced by audiovisual and tactile stimulation and the plasma concentrations of NE and E were determined by means of a radioimmunoassay (RIA). RESULTS: A significant (p <0.001) reduction of NE in CC plasma was found from flaccidity (362 + or - 173 pg./ml.) to rigidity (248 + or - 122 pg./ml.), followed by an increase in the detumescence phase (336 + or - 199 pg./ml.), (p <0.001). In contrast, changes in NE levels in the peripheral plasma were less pronounced from 1P (202 + or - 102 pg./ml.) to 3P (229 + or - 118 pg./ml.), (p = 0.006) and from 3P to 4P (222 + or - 127 pg./ml.), respectively (p = 0.370). The most pronounced increase in cavernous E levels were observed from flaccidity (47 + or - 41 pg. /ml.) to tumescence (130 + or - 106 pg./ml.) (p <0.001). Cavernous E levels dropped significantly from 113 + or - 67 pg./ml. during rigidity to 76 + or - 57 pg./ml. + or - during detumescence (p <0.001). The course of peripheral plasma levels of E was similar to that in the cavernous blood. Mean peripheral E level was 69 + or - 55 pg./ml. in the state of penile flaccidity, reaching 98 + or - 78 pg./ml. in tumescence and 82 + or - 64 pg./ml. in rigidity (p <0.001), respectively, and finally decreasing to 62 + or - 46 pg./ml. in detumescence. CONCLUSION: Penile erection, based on the relaxation of cavernous and arterial smooth muscle, is accompanied by a significant reduction of NE in cavernous blood, while E levels rose in peripheral and cavernous blood during developing erection.     

Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery

Contractant and relaxant effects of prostaglandins (PG) F2 alpha, E1 and E2, prostacyclin (PGI2), the thromboxane A2 agonist U46619 and the prostaglandin endoperoxide analogue U44069 were investigated in isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery. In corpus cavernosum and corpus spongiosum preparations, PGF2 alpha produced concentration-dependent contractions showing rhythmic variations in tension. The contractions were effectively relaxed by carbachol and vasoactive intestinal polypeptide. U46619, U44069 and PGI2 also contracted corpus cavernosum and corpus spongiosum strips at resting tension, U46619 being the most potent drug. PGE1 and PGE2, but not PGI2 relaxed corpus cavernosum and corpus spongiosum preparations contracted by noradrenaline (NA) and PGF2 alpha. PGE1 was the more effective agent; high concentrations of PGE2 produced contraction. In cavernous artery segments, PGF2 alpha produced concentration-dependent contractions. No oscillations in tension were observed; carbachol had no relaxant action, but VIP effectively relaxed the vessels. U46619 and U44069, but not PGI2 had contractant effects on cavernous artery segments at resting tension. PGE1 and PGI2, but not PGE2 relaxed NA contracted vessel preparations; all agents (PGE2 less effectively) relaxed PGF2 alpha contracted vessel segments. It is concluded that cavernous artery and erectile tissue proper (corpus cavernosum and corpus spongiosum) differ importantly in their reaction to various prostanoids. It cannot be excluded that products of the arachidonate cascade can be involved in the control of penile tumescence and erection.     

Human penile hemodynamics studied by a polarographic method

Observations of the tissue oxygen tension alteration were made using an open tip type oxygen electrode polarographic method as an index of blood flow change in the penile skin, corpus cavernosum and thigh skin of 16 males aged 20-26 years (average age: 20.5 years). In another five males aged 18-21 (average age: 19.8 years) the relationship between corpus cavernosum tissue oxygen tension alteration and penile circumference change in the erection process was observed. This relation was obtained in the penile circulation model, and penile hemodynamics were ascertained. In the flaccid penis the corpus cavernosum contains low-oxygen blood and there is a blockade at the vascular tree in the corpus cavernosum. In the tumescence phase the blood flow of the corpus cavernosum increased suddenly by the relief of cavernosum vascular blockade. During the penile tumescence phase the increased inflow and outflow persisted in corpus cavernosum, and in penile skin the blood also increased initially, but gradually decreased as penile circumference increased. After erection was attained it is thought that resistance to inflow occurred by outflow pathway contraction. In the detumescence phase, a decrease of inflow and a concomitant increase of outflow occurred and the reopening of outflow is thought to be necessary for prompt penile detumescence.     

Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries—immunohistochemical distribution and functional significance

Objectives: It has been well established that male erectile dysfunction is frequently associated with vascular diseases. The normal function of cavernous arteries is considered a prerequisite to maintain sufficient blood flow to the trabecular spaces in order to enable penile erection. Contractility of cavernous arteries is regulated by the peripheral autonomic nervous system and endogenous factors released from the endothelial cell layer. A significant increase of blood flow in the central cavernous arteries is the initial event leading to penile tumescence and rigidity. Besides the significance of the nitric oxide/cyclic guanosine monophosphate (cGMP)-mediated mechanisms, the cyclic AMP (cAMP) signalling pathway is also involved in the regulation of tone of the erectile tissue, and interactions between cGMP- and cAMP-mediated mechanisms have been demonstrated. The aim of the present study was to investigate by means of immunohistochemistry the presence of the phosphodiesterase (PDE) isoenzymes 3, 4 (cAMP-specific PDEs) and 5 (cGMP-specific PDE) in thin sections of human central cavernous arteries (HCA) and their functional significance in the mechanism of vessel tone regulation. Methods: Functional experiments were performed using circular segments of HCA and strip preparations of the human corpus cavernosum (HCC). Relaxant effects induced by the cumulative addition of the PDE inhibitors milrinone (PDE3 inhibitor), rolipram (PDE4 inhibitor) and sildenafil (PDE5 inhibitor; 0.01, 0.1, 1 and 10 M) were studied in preparations of HCA and HCC challenged by 1 M norepinephrine (NE). Moreover, immunohistochemistry was carried out in order to evaluate the expression of PDE3, PDE4 and PDE5 in thin sections of HCA. Results: Milrinone, rolipram and sildenafil dose-dependently reversed the NE-induced tension of the isolated vascular segments and HCC strips with sildenafil being the most effective drug. Neither rolipram nor milrinone reached an EC₅₀ value. Abundant immunoreactivities specific for PDE3, PDE4 and PDE5 were observed in the entire smooth musculature of the wall of HCA and resistance arteries. In addition, immunoreactivity for PDE4 was also detected in the cytoplasm of endothelial cells lining the cavernous arteries. Conclusions: The cGMP-dependent relaxation of cavernous arteries is not only dependent on the normal function of the peripheral autonomic nervous system but also on the functional integrity of the vascular endothelium. The expression of the cGMP-specific PDE5 and the ability of the PDE5 inhibitor sildenafil to reverse the adrenergic tension of isolated segments of HCA underline the important role of the NO/cGMP pathway in the control of smooth muscle tone of human trabecular smooth musculature and penile cavernous arteries. Our results also suggest a significance of the cAMP-dependent signaling mechanisms in the regulation of tension of central HCAs. The present findings are also in support of the hypothesis of interactions between the cGMP- and cAMP-mediated signaling pathways in HCAs. Further investigations are indicated in order to outline potential differences between central HCAs and helicine resistance arteries. This may help to understand better the relations between structural and functional changes in the penile erectile tissue in patients with cardiovascular diseases and endothelial dysfunction.     

Oxytocin plasma levels in the systemic and cavernous blood of healthy males during different penile conditions

It is well established that transmitters of the nonadrenergic-noncholinergic (NANC) system are involved in the control of sexual arousal and penile erection in healthy males. The proerectile activity of dopamine D1/D2 receptor agonist apomorphine-HCl (IXENSE, UPRIMA) involves oxytocinergic pathways descending from the hypothalamus to the brain stem and spinal autonomic centers. Although it has been demonstrated that injection of oxytocin into the paraventricular nucleus and the hippocampus produces penile erection in rats, the significance of the peptide in the control of sexual arousal and penile erection in man has been, up until now, only poorly evaluated. The present study was undertaken to determine whether oxytocin (OT) plasma levels alter in the systemic and cavernous blood of healthy males under different penile conditions (flaccidity, tumescence, rigidity, detumescence). Twenty-five healthy adult males were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and rigid erection. Blood was taken from the corpus cavernosum (CC) and the cubital vein (CV) during penile flaccidity, tumescence, rigidity and detumescence. Following extraction from plasma aliqouts, oxytocin was measured by means of a radioimmunoassay. An increase was observed in the mean OT plasma levels in the systemic and cavernous blood when the flaccid penis became tumescent (CC: from 66.7+/-34 to 75+/-44 pg/ml; CV: from 71+/-41 to 79+/-49.5 pg/ml). From tumescence to rigidity, OT further rose in the cavernous blood (to 81+/-58 pg/ml), whereas it remained unaltered in the systemic circulation. During detumescence, oxytocin plasma levels dropped in the cavernous but again increased in the systemic blood (to 94+/-49 pg/ml). Our results support the hypothesis of a pivotal role of OT in the mechanism of male sexual arousal and penile erection and provide a rationale for the use of apomorphine in the treatment of erectile dysfunction.     

Systemic and cavernous plasma levels of vasoactive intestinal polypeptide during sexual arousal in healthy males

Results from basic research scrutiny indicate a role for non-adrenergic, non-cholinergic transmitters, among which there are various peptides, in the physiology of normal male sexual function. Nevertheless, it is not yet known which particular peptides are essentially involved in maintaining sexual arousal and regulating penile tumescence and rigidity in adult males. Vasoactive intestinal polypeptide (VIP), a peptide with smooth muscle relaxing properties, is considered to be one of the factors that contributes to such control. The present study was performed to evaluate the significance of VIP in normal male sexual function. We determined the plasma levels of VIP in the systemic and cavernous blood of 54 healthy adult male volunteers, who were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and erection. Whole blood was aspirated from the corpus cavernosum and the cubital vein during penile flaccidity, tumescence, rigidity and detumescence, and VIP was quantified in plasma aliquots by means of a radioimmunoassay. Of the 54 volunteers, 16 were permitted to masturbate and ejaculate, and blood was then again withdrawn from the cavernous meshwork and the cubital vein in order to measure VIP. All VIP levels were registered within the normal physiological range from 3.0-30 pmol/l. No increase in median VIP plasma levels was observed in the systemic and cavernous blood when the flaccid penis became rigid. During penile detumescence, mean cavernous VIP level increased to 11.9+/-7.8 pmol/l (baseline: 8.6+/-3.0 pmol/l), whereas VIP remained unaltered in the systemic circulation. Following ejaculation, mean VIP level in the cavernous blood was elevated to 25.3+/-10.9 pmol/l, whereas, in the systemic blood, no significant changes were registered. Our results support the hypothesis that VIP plays a functional role in the mechanism of male sexual arousal. Nevertheless, our data indicate that the peptide is not the main non-adrenergic, non-cholinergic mediator of penile tumescence and rigidity in human males.     

Is serotonin significant for the control of penile flaccidity and detumescence in the human male?

For more then 15 years, there has been speculation on the significance of serotonergic pathways in the control of male sexual function, especially in the maintenance of penile flaccidity and the initiation of detumescence. However, only a few in vivo studies on peripheral serotonergic transmission have been carried out. The aim of the present study was to evaluate further the effects of serotonin (5-HT) on isolated human erectile tissue and to detect serum levels of 5-HT in the systemic and cavernous blood taken during different penile conditions from healthy males. The effects of 5-HT on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. A total of 41 healthy, adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of 5-HT (ng/ml) were determined by means of an enzyme-linked immunosorbent assay. The cumulative addition of 5-HT (0.001-10 microM) induced contraction in the isolated HCC strips. The contractile response was abolished in the presence of 5-HT(1alpha)-receptor antagonist NAN-190. No attenuating effect of 5-HT was observed on electrically induced relaxation of the tissue. Moreover, amplitudes of relaxation remained unaltered in the presence of NAN-190. In the healthy volunteers, a significant increase in 5-HT levels was detected in the cavernous serum from flaccidity (113+/-62) to tumescence and rigidity (140+/-69 and 141+/-54, respectively), followed by a decrease in the detumescence phase (123+/-79). Changes in 5-HT levels in the systemic serum were less pronounced. Under all penile conditions, systemic 5-HT levels were higher than those registered in the cavernous serum. Although 5-HT does not appear to be involved in postsynaptic transmission in the HCC, our results may provide evidence for a physiological significance of 5-HT in the control of penile flaccidity and detumescence. Thus, our findings may give a rationale for the use of 5-HT antagonists in the pharmacotherapy of erectile dysfunction.     

Is β‐endorphin significant in the control of the male sexual response?

It has been assumed that β‐endorphin, belonging to the family of opiodergic neuropeptides, might facilitate the inhibition of the male sexual response; however, its role in the control of the penile erectile tissue remains to be elucidated. This study aimed to evaluate in healthy men the course of β‐endorphin in the systemic and cavernous blood through different stages of sexual arousal. Thirty‐four (34) men were exposed to erotic stimuli to induce penile tumescence and rigidity. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Plasma levels of β‐endorphin were determined by means of radioimmunometric methods. The effects of β‐endorphin on isolated human penile erectile tissue were investigated in vitro. β‐endorphin did not induce a contractile response of the cavernous tissue or reverse the contraction induced by noradrenaline. β‐endorphin decreased in the systemic blood when the penis became tumescent and rigid and increased during detumescence. In the cavernous blood, no alterations in β‐endorphin concentrations were observed. The drop in β‐endorphin observed during tumescence and rigidity seems likely to reflect the inhibition of the opioidergic input with the beginning of sexual arousal.     

Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum.

Nitric oxide (NO) caused a potent, marked, and transient relaxation of precontracted strips of corpus cavernosum isolated from humans and rabbits. The relaxation response elicited by NO was very similar to the relaxation evoked by electrical field stimulation via the nonadrenergic-noncholinergic pathway. Sodium nitroprusside, nitroglycerin, and S-nitroso-N-acetylpenicillamine, which are nitrovasodilators known to generate NO, also caused marked concentration-dependent relaxation of corpus cavernosum. Relaxant responses to NO were enhanced by the cyclic GMP phosphodiesterase inhibitor M&B 22,948 and inhibited by oxyhemoglobin. Similarly, relaxation of corpus cavernosum in response to electrical field stimulation or acetylcholine was enhanced by M&B 22,948 and inhibited by oxyhemoglobin. NO stimulated cyclic GMP formation in corpus cavernosum and a close positive correlation was found between the magnitudes of relaxation and cyclic GMP formation. The data suggest that NO-elicited activation of guanylate cyclase and cyclic GMP formation represents the signal transduction mechanism responsible for relaxation and nonadrenergic-noncholinergic-mediated penile erection. These observations indicate that NO is a potent relaxant of human and rabbit corpus cavernosum and support our hypothesis that endogenous NO is the principal mediator of penile erection caused by nonadrenergic-noncholinergic stimulation.     

Erectile mechanism studied using penile vascular casts in the dog

The possible mechanism of penile erection was discussed based on the findings obtained by the scanning electron microscope observations of the penile vascular casts in the dog. Polsters protruding into the lumen of the distal helicine arteries regulate blood flow into the cavernous spaces. The drainage veins from the corpus cavernosum penis arose on the dorsal surface and crept on the corpus until changing direction perpendicularly. This suggested that these veins were efficiently compressed between the tunica albuginea and the corpus cavernosum penis during erection. For a high pressure to be maintained in the cavernous spaces during erection, a closed system separated from the systemic circulation must be required.     

Is there an inhibitory role of cortisol in the mechanism of male sexual arousal and penile erection?

Background. It has been speculated for more than 2 decades whether there is a significance of adrenal corticosteroids, such as cortisol, in the process of normal male sexual function, especially in the control of sexual arousal and the penile erectile tissue. However, only few in vivo studies have been carried out up until now on the effects of cortisol on human male sexual performance and penile erection. In order to evaluate further the role of cortisol in male sexual activity, the present study was conducted to detect serum levels of cortisol in the systemic and cavernous blood taken during different penile conditions from healthy males. Material and Methods. The effects of cortisol derivative prednisolone, catecholamine norepinephrine (NE) and the peptide endothelin-1 (ET-1) on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. Fifty-four healthy adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of cortisol (g/dl) were determined by means of a radioimmunoassay (ELISA). Results. In the healthy volunteers, cortisol serum levels significantly decreased in the systemic circulation and the cavernous blood with increasing sexual arousal, when the flaccid penis became rigid. During detumescence, the mean cortisol level remained unaltered in the systemic circulation, whereas in the cavernous compartment, it was found to decrease further. Under all penile conditions, no significant differences were registered between cortisol levels in the systemic circulation and in the cavernous blood. Cumulative addition of NE and ET-1 (0.001–10 M) induced contraction of isolated HCC strips, whereas the contractile response to prednisolone was negligible. Conclusion. Our results strongly suggest an inhibitory role for cortisol in the mechanism of male sexual response and behaviour. These properties are mediated rather via an effect on central structures than on the penile erectile tissue. Future studies to include patients suffering from erectile dysfunction may reveal whether or not there are differences in the cortisol serum profiles of healthy subjects and patients under different stages of sexual arousal.     

The rat as a model for the study of penile erection

A model has been developed for the study of penile erection in the Sprague-Dawley rat. Anatomical dissections demonstrate a bilateral ganglion lateral to the prostate called the major pelvic ganglion. This ganglion receives input from the pelvic and hypogastric nerves and innervates the pelvic viscera. A large fiber from the major pelvic ganglion courses along the urethra and innervates the corpus cavernosum, the cavernous nerve. In 40 animals, electrical stimulation of either the cavernous nerve or the pelvic nerve resulted in reproducible repetitive tumescence of the corpora cavernosum. Following ablation of the cavernous nerve, electrical stimulation failed to produce erections. Standard mating behavior tests of mounting, intromission and ejaculation in 38 rats showed that surgical ablation of the cavernous nerve resulted in a decrease in the rate of intromissions and ejaculations compared with sham operated controls. Present models for the study of erection have been limited to the dog, monkey and cat. The rat model presented here offers several advantages over these existing models: 1) the cavernous nerve is easily identified, 2) electrical stimulation is easily accomplished and reproducible, 3) behavioral and neurophysiological studies are possible, and 4) animal purchase, housing, and maintenance costs are low. These advantages make this model a uniquely useful tool in the further study of penile erection.     

Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum tissue: synergism of nitric oxide and YC-1

Nitric oxide (NO) activates corpus cavernosum smooth muscle soluble guanylate cyclase (sGC) and increases the synthesis of cGMP that results in smooth muscle relaxation and ultimately, penile erection. To characterize sGC and define the potential synergy between NO and the allosteric activator YC-1 in corpus cavernosum, rat sGC was activated by either sodium nitroprusside (SNP) or YC-1, and YC-1 potentiated the effects of SNP with a 200-fold activation of sGC. Both SNP and YC-1 decreased the Km and increased the Vmax. ODQ significantly inhibited sGC activated by SNP with IC50 of 0.5 nM, but did not affect the sGC activated by YC-1 as well as basal sGC activity. SNP and YC-1 synergistically increased intracellular cGMP levels in rabbit corpus cavernosum smooth muscle cell cultures. YC-1 significantly relaxed rabbit cavernosum tissue strips in organ baths with an EC50 of 8.4 microM. In the presence of L-nitroarginine methyl ester to block endogenous NO production, co-administration of SNP shifted the dose response of YC-1 to the left, showing the synergism of SNP and YC-1 in tissue strips. In view of the clinical efficacy of phosphodiesterase-5 inhibitors, activation of sGC may provide an alternative means for enhancing the activity of neurally derived NO during sexual stimulation in the corpus cavernosum, representing a novel approach for the treatment of erectile dysfunction.