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.     

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.     

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.     

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.     

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 endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction

 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 are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA). Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2–0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52 ± 0.38 fmol/ml vs. 0.48 ± 0.46 fmol/ml, respectively; detumescence: 0.53 ± 0.33 fmol/ml vs. 0.27 ± 0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.     

Systemic and cavernosal plasma levels of endothelin (1–21) during different penile conditions in healthy males and patients with erectile dysfunction

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 are involved in this process. The peptide endothelin-l (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated that ET-1 might be involved in the pathophysiology of penile erection. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels recorded in systemic and cavernosal blood taken from healthy males and patients with erectile dysfunction (ED) during different penile conditions (flaccidity, tumescence/rigidity, detumescence). The study groups comprised 33 healthy adult males and 25 patients. The subjects were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET- 1/-2 was determined in plasma aliquots by means of an enzyme-linked immunosorbent assay (ELISA). Mean systemic and cavernosal plasma levels of ET- 1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernosal blood during penile tumescence, rigidity and detumescence. In the patients, mean plasma ET-1/-2 levels during penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernosal blood (flaccidity 0.52 +/- 0.38 fmol/ml vs 0.48 +/- 0.46 fmol/ml, respectively: detumescence 0.53 +/- 0.33 fmol/ml vs 0.27 +/- 0.11 fmol/ ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and those with a psychogenic aetiology of ED. During detumescence, the mean ET-1/-2 level was lower in the cavernosal blood taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-l/-2 in the cavernosal blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seemed to be of no physiological significance, our findings contradict the hypothesis of the ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding the involvement of ET-1 in the pathophysiology of erectile dysfunction.     

Course of transforming growth factor ß1 in the systemic and cavernous blood of healthy males through different penile conditions

Studies on erectile dysfunction (ED) have revealed a relationship between smooth muscle atrophy and the accumulation of collagen in the corpus cavernosum (CC). Transforming growth factor ß1 (TGF ß1) is a cytokine which has been proposed to be involved in the fibrotic process in the CC. We aimed to evaluate the course of TGF ß1 in the systemic and cavernous blood of 17 healthy males through different phases of the sexual arousal response (exemplified by the penile conditions flaccidity, tumescence, rigidity and detumescence). An enzyme‐linked immunoassay was used to measure the concentration of TGF ß1 (ng/ml) in both the systemic and cavernous blood at the stages of flaccidity, tumescence and detumescence. TGF levels were significantly higher in the cavernous compartment than in the systemic blood. A linear decrease was evident in the cavernous blood when the flaccid penis became tumescent (24.3 ± 14.5 to 13.9 ± 6.5) and rigid (to 8.7 ± 3.1). At detumescence, TGF increased to 18.3 ± 10.4. In contrast, the levels in the systemic circulation remained unchanged. The results are in support of the hypothesis that the concentration of TGF ß1 in the CC is regulated by adequate blood flow and oxygenation.     

Possible role of human growth hormone in penile erection

PURPOSE: Treatment with recombinant human growth hormone in adult patients with growth hormone deficiency increases nitric oxide and cyclic guanosine monophosphate (cGMP). We examined the functional in vitro effects of recombinant human growth hormone on tissue tension and cyclic nucleotide levels of human corpus cavernosum and detected changes in growth hormone in the cavernous and peripheral blood during different phases of penile erection. MATERIALS AND METHODS: Relaxant responses of human corpus cavernosum were investigated using the organ bath technique. Tissue levels of cGMP were determined by a specific radioimmunoassay after dose dependent exposition of isolated human corpus cavernosum strips to recombinant human growth hormone. In 35 healthy potent volunteers blood samples were obtained simultaneously from the corpus cavernosum and cubital vein during different functional conditions of the penis, including flaccidity, tumescence, rigidity and detumescence. Penile erection was induced by audiovisual and tactile stimulation. Serum growth hormone was determined by an immunoradiometric assay. RESULTS: Recombinant human growth hormone elicited dose dependent relaxation of human corpus cavernosum strips in vitro. The relaxing potency of recombinant human growth hormone was paralleled by its ability to elevate intracellular levels of cGMP. In vivo the peripheral growth hormone serum profile of the respective penile conditions did not significantly differ from those of cavernous serum. The main increase in growth hormone to greater than 90% was determined during developing penile tumescence, followed by a transient decrease afterward. CONCLUSIONS: These results suggest that penile erection may probably be induced by growth hormone through its cGMP stimulating activity on human corpus cavernosum smooth muscle.     

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 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 neuropeptide Y during sexual arousal in healthy males

Neuropeptide Y (NPY) has been shown to induce contraction of isolated human penile erectile tissue and potentiate the response to noradrenaline. The purpose of our study was to measure in the cavernous and systemic blood of healthy male volunteers the course of NPY through different stages of sexual arousal. Whole blood was drawn simultaneously from the corpus cavernosum and the cubital vein of 16 healthy male volunteers during penile flaccidity, tumescence, rigidity and detumescence. Tumescence and erection were induced by applying audiovisual and tactile stimulation. Plasma levels of NPY (given in pmol l(-1)) were determined by means of an enzyme-linked immunoassay. NPY significantly decreased in the cavernous blood on sexual arousal, when the flaccid penis became tumescent and, finally, rigid (F: 88.8 ± 35.8, T: 62.4 ± 22.7, R: 62.3 ± 19.7), and only slightly rose in the phase of detumescence (64.8 ± 23). In the systemic circulation, no pronounced alterations in the concentration of NPY were registered (F: 64.4 ± 27, T: 65.8 ± 19, R: 59.6 ± 25, D: 67.6 ± 29.3). Our findings are in favour of the hypothesis that NPY could contribute to the maintenance of the resting state of cavernous smooth muscle.     

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.     

Electrical activity of corpus cavernosum during flaccidity and erection of the human penis: a new diagnostic method?

We investigated 7 normal men and 1 diabetic patient with erectile dysfunction. Electromyography electrodes were placed in the corpus cavernosum of the penis and electrical activity was recorded during flaccidity. With sexual arousal the activity decreased and tumescence was initiated. During tumescence and full erection the electrical activity of the corpus cavernosum almost ceased but in the diabetic patient (neurogenic impotence) an increase was observed. This discoordination might be the cause of the erectile dysfunction. Recording the electrical activity of the corpus cavernosum in patients with suspected neurogenic erectile dysfunction could become clinically valuable, since this is the first test possible to study the function of the autonomic motor system that normally regulates penile function.     

Corpus cavernosum electromyography during morning naps in healthy volunteers: further evidence that corpus cavernosum potentials reflect sympathetically mediated activity

PURPOSE: We assessed the practicability of corpus cavernosum (CC) electromyography (EMG) in volunteers during morning naps in the laboratory and further validated this method. MATERIALS AND METHODS: A total of 11 healthy volunteers with a mean age of 23.8 years (range 19 to 31) were included. CC-EMG was started between 6:30 a.m. and 7 a.m. Two surface electrodes were placed at the base of the penis bilaterally and a reference electrode was placed on 1 kneecap. A strain gauge or Barlow gauge (Behavioral Technology, Salt Lake City, Utah) was used to monitor changes in penile circumference. Subjects were asked to sleep. Recording duration was 2 to 3 hours. Two recordings were performed per subject. RESULTS: Full erection was observed on 17 of the 22 recordings (77%), partial erection was noted on 3 (14%) and no tumescence was observed on the other 2 (9%). CC potentials consistently disappeared during tumescence and erection, while continuous CC potential oscillations reappeared during detumescence. During flaccidity bursts of CC potentials and electrical silence were recorded. Penile shrinkage was observed to accompany CC potentials but not to accompany electrical silence. CONCLUSIONS: CC-EMG during morning naps is a practical and valid method for investigating CC electrophysiology. CC-EMG signal patterns during tumescence, detumescence and flaccidity fit the existing theory that CC potentials reflect cavernous smooth muscle sympathetically mediated activity.     

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.     

Determination of nitric oxide metabolites by means of the Griess assay and gas chromatography–mass spectrometry in the cavernous and systemic blood of healthy males and patients with erectile dysfunction during different functional conditions of the penis

Recent research implicated that the relaxation of cavernous arterial and trabecular smooth muscle – the crucial event in penile erection – is initiated by the release of nitric oxide (NO) from nerve terminals within the cavernous tissue as well as from the endothelia that line the lacunar spaces and the intima of penile arteries. The present study was undertaken to determine whether plasma levels of the NO metabolites nitrate (NO⁻ ₃) and nitrite (NO⁻ ₂) in the systemic and cavernous blood of male subjects change during different penile conditions, and whether there is a difference in the NO⁻ ₃ and NO⁻ ₂ levels of normal males and patients with erectile dysfunction (ED). Twenty-four potent adult male volunteers and 15 patients with ED were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and NO⁻ ₃ and NO⁻ ₂ levels were determined in plasma aliquots by means of the Griess reaction and a method combining gas chromatography and mass spectrometry (GC-MS). The mean systemic and cavernous plasma NO₃ ⁻/NO₂ ⁻ level in blood samples obtained from the healthy volunteers was 25–31 μM when determined by means of the Griess reaction and 37–41 μM when measured by GC-MS. Both approaches revealed that NO₃ ⁻/NO₂ ⁻ levels in the peripheral and cavernous blood do not change appreciably during developing erection, rigidity and detumescence. Moreover, no significant differences were found between NO₃ ⁻/NO₂ ⁻ plasma levels in the systemic and cavernous blood samples taken from the normal subjects and patients during penile flaccidity, tumescence and detumescence. Our results may reflect the fact that NO metabolism in the corpora cavernosa in the phases of penile tumescence and rigidity may account for only a minor fraction of local levels of NO₃ ⁻ and NO₂ ⁻, which may also derive from exogenous sources. Moreover, the basal levels of NO metabolites in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection could conceal any release of NO that may occur within the penile tissue. Thus, we conclude that the quantification of NO metabolites by means of advanced detection methods, such as GC-MS, is of no use in the workup of ED. Received: 2 May 2000 / Accepted: 27 July 2000     

Single potential analysis of cavernous electrical activity in impotent patients: a possible diagnostic method for autonomic cavernous dysfunction and cavernous smooth muscle degeneration

Cavernous electrical activity was recorded in 214 patients with erectile dysfunction and in 39 normal patients. In 34 of the 39 normal patients potentials of a uniform shape were recorded during flaccidity. At cutoff frequencies of 0.5 to 500 Hz. the duration was 8 to 18 seconds (mean 12.8 +/- 2.8, seconds, standard deviation), the amplitude was 250 to 750 microv. (mean 444 +/- 109 microv.) and the polyphasity was 8 to 22 (mean 13.8 +/- 3.3). With increasing tumescence and rigidity during audiovisual sexual stimulation, high frequency potentials of low amplitude and short duration were found in the normal patients. In impotent patients with an upper motor neuron or peripheral lesion specific types of potentials were observed. In 11 of 14 impotent patients with insulin-dependent diabetes for more than 20 years and with clinical findings of cavernous myopathy the potentials showed low amplitude, irregular shape and slow depolarizations. Abnormal findings of cavernous electrical activity were recorded in 51.6% of the consecutive impotent patients. Our clinical study suggests that single potential analysis of cavernous electrical activity may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.     

Corpora cavernosa ultrastructure in vascular erectile dysfunction

Open biopsy of the corpus cavernosum was performed in 13 nondiabetic patients with erectile dysfunction. The history and physical examination, sleep rigidity and tumescence monitoring, hormonal assays, duplex ultrasonography with papaverine, and cavernosometry and cavernosography, formed the basis of categorizing each patient into 1 of 5 etiological groups. These groups included neurogenic, moderate arterial, severe arterial, venous and fibrotic causes for organic erectile dysfunction. The cavernous smooth muscle and endothelium in each patient appeared to be normal on light and electron microscopy. We conclude that cavernous biopsy is of limited value to determine therapeutic options in patients with erectile dysfunction.