Human Penile Erection Research Articles

VACUUM THERAPY – PREVENTION OF HYPOXIA OF CAVERNOUS TISSUE PATIENTS AFTER RADICAL PROSTATECTOMY

Patients, after radical prostatectomy with the use of nerve-sparing techniques, without carrying out penile rehabilitation, are at risk of forming cavernous fibrosis with the emergence of subsequent persistent erectile dysfunction. In order to minimize damage to cavernous tissue and early restoration of erectile function during the period of neuropraxia, it is necessary to ensure a sufficient level of oxygenation. The role of applying vacuum in penile rehabilitation for the prevention of hypoxia of cavernous tissue is not fully understood, due to the lack of data on the gaseous composition of the blood at the time of reaching the vacuum of erection. The purpose of this work was to review the scientific studies devoted to the study of vacuum induced penile erection in animals or humans, which indicates high results due to increased oxygenation of cavernous tissue.

Potential negative effects of anti-histamines on male reproductive function.

Histamine (HA) is a pleiotropic biogenic amine synthesized exclusively by histidine decarboxylase (HDC) in most mammalian tissues. The literature on the role of HA within the male gonad has expanded over the last years, attracting attention to potential unexpected side-effects of anti-histamines on testicular function. In this regard, HA receptors (HRH1, HRH2 and HRH4) have been described in Leydig cells of different species, including human. Via these receptors, HA has been reported to trigger positive or negative interactions with the LH/hCG signaling pathway depending upon its concentration, thereby contributing to the local control of testicular androgen levels. It should then be considered that anti-histamines may affect testicular homeostasis by increasing or decreasing steroid production. Additionally, HRH1 and HRH2 receptors are present in peritubular and germ cells, and HRH2 antagonists have been found to negatively affect peritubular cells and reduce sperm viability. The potential negative impact of anti-histamines on male reproduction becomes even more dramatic if we consider that HA has also been associated with human sexual behavior and penile erection. What is more, although testicular mast cells are the major source of locally produced HA, recent studies have described HDC expression in macrophages, Leydig cells and germ cells, revealing the existence of multiple sources of HA within the testis. Undoubtedly, the more we learn about the testicular histaminergic system, the more opportunities there will be for rational design of drugs aimed at treating HA-related pathologies, with minimum or nule negative impact on fertility.

Screening of new compounds for the management of erectile dysfunction

Objective/Background: Erectile dysfunction, a male sexual dysfunction generally develops due to impairment of relaxation of penile smooth muscles and arteries. Inhibitors of phosphodiesterase type 5 (PDE5) enzyme like in sildenafil, vardenafil, tadalafil etc. are in clinical use for the management of erectile dysfunction. Ongoing research focuses on development of potent medicine with fewer side effects. Objective of this article is to discuss and demonstrate procedures available to screen new compounds for the management of erectile dysfunction. Methodology: Many animal models (mice, rat, cat, rabbit, dog etc.) are available to screen new chemical compounds for increasing erectile function. In vitro (using isolated corpus cavernosum smooth muscle of penile tissue) and in vivo (measuring intracavernosal pressure) studies may be performed for screening new compounds. In this article, we discuss about two such screening procedures using rat as an animal model. Results and discussion: Compounds those relax isolated rat corpus cavernosum smooth muscles significantly in vitro may increase penile erection in humans. Similarly, the compounds those increase intracavernosal pressure by relaxing erectile smooth muscle and penile arteries in rat may increase erectile function in humans. Conclusion: Rat is a suitable model for screening new compounds to manage erectile dysfunction. Key words: Corpus cavernosum smooth muscle, intracavernosal pressure, mean arterial pressure.

Brain potentials related to the human penile erection

The aim of this study was to elucidate the brain processes preceding penile responses. Electroencephalographic (EEG) potentials and penile circumference were recorded simultaneously while male subjects were exposed to visual sexual stimuli (VSS). The trials were sorted by the penile response of the subjects (erection, maintenance or detumescence). The corresponding EEG recordings were then subjected to independent component analysis. We found that 200 ms after VSS onset brain potentials differ according to the genital response to follow. Whereas early posterior negativity (EPN) was predominantly related to erection and maintenance, P3-like activity was found to precede detumescence. EPN indicates a more 'emotional' processing state of the brain, whereas P3-like activity related to detumescence indicates a more 'cognitive' processing state. The latter is assumed to reflect activity of the locus coeruleus-norepinephrine system. Further research should evaluate the contribution of P3-related brain activity to psychogenic erectile dysfunction.

Effect of aldosterone on isolated human penile corpus cavernosum tissue

To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue. Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21-75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues. Aldosterone caused no significant change in resting tension and did not affect the nitric oxide-dependent relaxation reaction. However, the dose-response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 x 10(-5)M) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti-aldosterone agent) was added as a pre-treatment. Pre-treatment with aldosterone also significantly extended the mean (SEM) time required to reach 50% relaxation of a noradrenaline-induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002). Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline-induced contraction. The effect on the noradrenaline-induced contraction is probably caused by aldosterone enhancing the affinity of the alpha-receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.

Nuclear medicine imaging technique in the erectile dysfunction evaluation: a mini-review

Functional imaging with positron emission tomography and single photon emission computed tomography is capable of visualizing subtle changes in physiological function in vivo. Erectile dysfunction(ED) diminishes quality of life for affected men and their partners. Identification of neural substrates may provide information regarding the pathophysiology of types of sexual dysfunction originating in the brain. The aim of this work is to verify the approaches of the nuclear medicine techniques in the evaluation of the erectile function/disfunction. A search using the words ED and nuclear medicine, ED and scintigraphy, ED and spect and ED and pet was done in the PubMed. The number of citations in each subject was determined. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. To tackle problems such as hyposexual disorders or ED caused by brain disorders, it is crucial to understand how the human brain controls sexual arousal and penile erection.

Brain Processing of Audiovisual Sexual Stimuli Inducing Penile Erection: A Positron Emission Tomography Study

Penile erection is dependent on commands from the central nervous system. Although basic studies of animals and neuroimaging studies of humans have been conducted to identify key brain regions associated with sexual arousal, to our knowledge no reliable studies of the first excitation phase of sexual arousal leading to penile erection have been reported. We used H(2)(15)O-positron emission tomography to analyze regional cerebral blood flow just before penile erection in heterosexual volunteers. The subjects viewed 3 different types of audiovisual materials-sexually explicit clips, nonsexual neutral clips and dynamic mosaic image control clips-presented in random order, and penile rigidity was monitored in real time with a RigiScan(R) Plus device. Positron emission tomography scanning was initiated simultaneously when each clip was started, and images obtained when the subjects showed appropriate penile response were analyzed and compared. The advanced audiovisual cortices and cerebellar vermis in the right hemisphere were activated for sexually explicit-dynamic mosaic image control clip contrast, and only the right middle frontal gyrus was activated for sexually explicit- nonsexual neutral clip contrast. Several primary visual and audio regions were activated for dynamic mosaic image control-sexually explicit clip contrast and nonsexual neutral-sexually explicit clip contrast. We speculate that advanced audiovisual activity with imagination, not primary visual and audio activity, occurs when men experience sexual arousal inducing penile erection. Furthermore, the cerebellar vermis may be a key region for induction of penile erection in humans.

1250: The Role of Cerebellar Activation in the Initiation of Human Penile Erection

1250: The Role of Cerebellar Activation in the Initiation of Human Penile Erection

Intracavernous pharmacotherapy for erectile dysfunction.

With the advent of phosphodiesterase type-5 inhibition as oral therapy, intracavernous injection of vasoactive agents has been relegated to second-line therapy for most patients with erectile dysfunction. However, the future of this category of agents remains bright as an ever-expanding number and combination of agents in use and under investigation will likely make intracavernous injection more appealing as greater efficacy, tolerability, and more rapid onset is attained. In this article, functional anatomy and physiology of human penile erection is reviewed, as are current clinical vasoactive agents including prostaglandin E-1, papaverine, and phentolamine. Emerging therapies discussed include guanylate cyclase activators, potassium channel openers, nitric oxide donors, vasoactive intestinal polypeptide, calcitonin gene-related peptide, selective alpha-1 receptor antagonists, and gene therapy. Ongoing research continues to define new roles for this effective and safe technique, which has withstood the test of time, restoring erectile function among patients with diverse ED etiologies and a variety of co-morbidities.

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

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. 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 (microg/dl) were determined by means of a radioimmunoassay (ELISA). 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 microM) induced contraction of isolated HCC strips, whereas the contractile response to prednisolone was negligible. 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 Relationship Of Serum Testosterone To Erectile Function In Normal Aging Men

We evaluated the variation in serum testosterone in normal aging men and its relationship with erectile function. In a study that was not community based and during a free screening program for prostate cancer 1,071 men were invited to complete a sexual activity questionnaire, that is the abridged 5-item version of the International Index of Erectile Function (IIEF-5), as a diagnostic tool for erectile dysfunction. Possible scores on the IIEF-5 are 1 to 25 and erectile dysfunction was classified into 5 categories based on the scores, namely severe-1 to 7, moderate-8 to 11, mild to moderate-12 to 16, mild-17 to 21 and none-22 to 25. Serum total testosterone was measured between 8:00 and 10:00 a.m. in all men. Of the 1,071 men 965 (90.1%) were included in this study, of whom 88% were white and 12% were black. Mean age was 60.7 years. In this sample the prevalence of all degrees of erectile dysfunction was estimated to be 53.9%. The degree of erectile dysfunction was mild in 21.5% of cases, mild to moderate in 14.1%, moderate in 6.3% and severe in 11.9%. According to age the erectile dysfunction rate was 36.4% in the 40 to 49, 42.5% in the 50 to 59, 58.1% in the 60 to 69, 79.4% in the 70 to 79 and 100% in the 80 years and older groups (p <0.05). The variation in mean serum total testosterone in the age groups was not statistically significantly different (p >0.05). Pearson coefficients of age and total testosterone did not reveal any significant correlation (r = 0.00376, p = 0.907), similar to IIEF-5 score and total testosterone (r = 0.0163, p = 0.612). However, analysis of the variables IIEF-5 and age showed a statistically significant inverse or negative relationship (r = -0.3449, p <0.05). Erectile dysfunction showed a clear association with aging but no consistent correlation of total testosterone with erectile condition was identified.

RENIN ANGIOTENSIN SYSTEM OF RABBIT CLITORAL CAVERNOSUM: INTERACTION WITH NITRIC OXIDE

Angiotensin (ANG) II has been known to be a potent modulator for the maintenance of smooth muscle tone of the penile cavernosum. However, its role in clitoral cavernosum is unknown. The clitoris is the homologue of the penis arising from the embryological genital tubercle. We investigated the presence of ANG II receptors, the function of ANG II, and its interaction with nitric oxide (NO) in rabbit clitoral cavernosum. The isometric tension was measured in the strips of clitoral cavernosum. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate expression of AT1a and AT1b ANG II receptor subtype mRNAs. In vitro autoradiography was used to localize ANG II receptors in the clitoral cavernosum. The clitoral cavernosum was contracted dose-dependently by the addition of ANG II. Dup 753 (ANG II type 1 receptor antagonist) inhibited significantly ANG II induced contraction. PD 123,319 (ANG II type 2 receptor antagonist) did not affect the ANG II response. Pretreatment with NG-nitro-L-arginine methyl ester (NO synthase inhibitor) accentuated contractions induced by ANG II. Specific binding sites for 125I-ANG II were found in the clitoral cavernosum. The dissociation constant (Kd) was 0.58 + or - 0.05 nM. Specific binding of 125I-ANG II was displaced by Dup 753 (10-5 M) but not by PD 123,319 (10-5 M). The inhibitory constant (Ki) for Dup 753 was 23. 4 + or - 9.73 nM and mRNAs for AT1a and AT1b receptor subtypes were detected by RT-PCR. The present study shows that ANG II is involved in the regulation of clitoral cavernosum smooth muscle tone via ANG II receptor subtype AT1, and that ANG II has cross-talk with NO.

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.

Characterization of ATP-sensitive potassium channels in human corporal smooth muscle cells.

Potassium (K) channels play a significant role in modulating human corporal smooth muscle tone, and thus, erectile capacity. Recent pharmacological studies indicate that the metabolically-regulated K channel (KATP) may be an important modulator of human penile erection with significant therapeutic potential. The goal of these initial studies, therefore, was to utilize patch clamp techniques to characterize the putative KATP subtype(s) present in cultured and freshly isolated human corporal smooth muscle cells. In the cell-attached patch mode, two distinct unitary K+ currents were identified whose respective conductance values were similar in cultured and freshly isolated smooth muscle cells. In cultured myocytes, the measured conductance values in symmetric KCl (140 mM) solutions were 59.1 +/- 2.7 pS and 18.4 +/- 2.1 pS (n = 5 cells). Under identical experimental conditions in freshly isolated myocytes, corresponding conductance values were 59.2 +/- 3.7 pS and 18.5 +/- 2.4 pS, respectively (n = 4 cells). I-V curves constructed during step depolarization (-60 to +80 mV), revealed a linear I-V relationship for both unitary conductances. Single channel records documented that both conductances were reversibly inhibited by the application of ATP (1-3 mM) to the bath solution in the inside-out attached patch configuration. The unitary activity of both K channel subtypes was significantly increased by the application of pinacidil (10 microM) and levcromakalim (10 microM). Whole cell patch recordings documented a glibenclamide-sensitive, pinacidil- and levcromakalim-induced increase in the whole cell outward K+ current during step depolarization (-70 mV to +130 mV) of 105 +/- 37%, 139 +/- 42%, respectively. These data confirm and extend our previous observations, and provide the first evidence for the presence of KATP channel subtypes in human corporal smooth muscle cells.

The neuropharmacology of yawning.

Yawning is a phylogenetically old, stereotyped event that occurs alone or associated with stretching and/or penile erection in humans and in animals from reptiles to birds and mammals under different conditions. Although its physiological function is still unknown, yawning is under the control of several neurotransmitters and neuropeptides at the central level as this short overview of the literature on the neurochemistry of yawning shows. Among these substances, the best known are dopamine, excitatory amino acids, acetylcholine, serotonin, nitric oxide, adrenocorticotropic hormone-related peptides and oxytocin, that facilitate yawning and opioid peptides that inhibit this behavioral response. Some of the above compounds interact in the paraventricular nucleus of the hypothalamus to control yawning. This hypothalamic nucleus contains the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas that play a key role in the expression of this behavioral event. When activated by dopamine, excitatory amino acids and oxytocin itself, these neurons facilitate yawning by releasing oxytocin at sites distant form the paraventricular nucleus, i.e. the hippocampus, the pons and/or the medulla oblongata. Conversely, activation of these neurons by dopamine, oxytocin or excitatory amino acids, is antagonized by opioid peptides, that, in turn, prevent the yawning response. The activation and inhibition, respectively of these oxytocinergic neurons is related to a concomitant increase and decrease, respectively, of paraventricular nitric oxide synthase activity. However, other neuronal systems in addition to the central paraventricular oxytocinergic neurons are involved in the control of yawning, since they do not seem to be involved in the expression of yawning induced by the stimulation of acetylcholine or serotoninergic receptors, nor by adrenocorticotropic hormone (ACTH) and related peptides. Nitric oxide is also involved in the induction of yawning by the latter compounds and neuronal links, for instance between dopamine and acetylcholine and dopamine and serotonin, seem to be involved in the yawning response. Finally, other neurotransmitters, i.e. gamma-aminobutyric acid (GABA) and noradrenaline, and neuropeptides, i.e. neurotensin and luteinizing hormone-releasing hormone (LH-RH), influence this behavioral response. In conclusion, in spite of some recent progress, little is known of, and more has to be done to identify, the neurochemical mechanisms underlying yawning at the central level.

Treatment of erectile dysfunction: Can pelvic muscle exercises improve sexual function?

Erectile dysfunction, the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, affects 10 to 20 million American men. The underlying causes of erectile dysfunction are commonly classified as neurogenic, arteriogenic, venogenic, or psychogenic. The perineal muscles, specifically the ischiocavernosus and bulbospongiosus, play a role in human penile erection. This article explores the role of pelvic muscle exercises, designed to strengthen the perineal muscles, in the treatment of erectile dysfunction secondary to venous leakage.

The role of histamine in human penile erection.

To investigate the relaxant action of histamine on human corpus cavernosum in vitro and the erectile response caused by the intracavernous injection of histamine in patients with psychogenic impotence. Human corpus cavernosum (HCC) tissue was cut into strips of approximately 2 cm and suspended in a cascade bioassay. The strips were then superfused with oxygenated and warmed Krebs solution and precontracted with noradrenaline (3 microM). Glyceryl trinitrate, acetylcholine and histamine were injected as a single bolus in the absence or in the presence of mepyramine and cimetidine. For the in vivo studies, histamine (30-60 micrograms) was injected intracavernously as a single bolus into the right corpus cavernosum 1 cm from the balamo-preputial sulcus. Similar protocols were carried out for papaverine (50 mg). The erectile response was divided into four grades: no response, tumescence, partial and full erection. In vitro studies demonstrated that histamine (3-100 micrograms) caused dose-dependent relaxation of the HCC strips which was significantly inhibited by cimetidine (5-10 microM). The histamine H1 receptor antagonist mepyramine (1 microM) potentiated histamine-induced relaxation. The co-infusion of both mepyramine and cimetidine did not abolish histamine-induced relaxation. When injected intracavernously in humans, histamine (30 micrograms) caused full erection in 13% of the patients, whereas 87% had partial erection or tumescence. A higher dose of histamine (60 micrograms) caused full erection in 26% of the patients and 74% had partial erection or tumescence. Papaverine induced full erection in the majority of patients (66%). In contrast to papaverine, the duration of erection induced by histamine was markedly shorter (mean 200 and 6.5 min, respectively). The penile erections induced by papaverine were associated with complications such as pain, haematoma and priapism. Histamine did not induce any complications. Treatment of eight male patients with psychogenic impotence with the histamine H1 receptor antagonist astemizol (10 mg orally once daily for 1 week) did not affect histamine-induced erectile responses. These results indicate that histamine may play a role in human penile erection. The erection-promoting action of histamine is probably due to H2 receptor activation, although another histamine receptor, possibly H3, also seems to be involved. This study suggests that histamine could be a valuable tool in the diagnosis of erectile dysfunction.

The relaxation of human corpus cavernosum caused by nitric oxide

Non-adrenergic non-cholinergic nerves (NANC) are thought to be important in the relaxation of corpus cavernosum for erectile function. On the other hand, it has been shown that nitric oxide (NO) is synthesized from L-arginine and released by the endothelium of blood vessels and accounts for the activity of endothelium-derived relaxing factor (EDRF). We studied whether electrical field stimulation (EFS) of isolated strips of human corpus cavernosum released NO and whether it could act as a NANC neurotransmitter. Human penile tissue specimens were mounted in an organ bath and the isometric tension recorded. EFS was applied to precontracted strips between two parallel platinum electrodes. Relaxation induced by EFS was not influenced by guanethidine or atropine, but was markedly inhibited by NG-nitro-L-arginine which is an analog of L-arginine that inhibits the conversion of L-arginine to NO, and hemoglobin which is an agent that inhibits the biological actions of NO. Methylene blue which is an inhibitor of cytosolic guanylate cyclase also reduced the relaxation of EFS, but not completely. The inhibitory effect of NG-nitro-L-arginine was reversed by addition of excess L-arginine. Exogenous NO relaxed human corpus cavernosum. The relaxation was only a transient response and concentration-dependent. The profile of responses is similar to that evoked by EFS. Our data clearly demonstrate the release of NO during EFS and the function of NO as a NANC neurotransmitter. Human penile erection may be mediated by NO generated in response to NANC neurotransmission.

Calcitonin-Gene-Related Peptide: A Possible Role in Human Penile Erection and its Therapeutic Application in Impotent Patients

A functional study was done to examine a possible role of calcitonin-gene-related peptide in human penile erection and its possible therapeutic applications for patients with erectile dysfunction. In the determination of an effective dosage, 5ng. (2 patients), 50ng. (2 patients), 500ng. (4 patients), 5μg. (4 patients) and 25μg. (7 patients) were injected intracavernously, and pulse and blood pressure were monitored. Arterial inflow was measured by Doppler sonography, smooth muscle relaxation was determined by the analysis of cavernous electrical activity and cavernous outflow occlusion was recorded by cavernosometry. In 12 patients the erectile response of prostaglandin E1 was compared to the response of an equal (6 patients) or decreased dose of prostaglandin E1 combined with an equal weight of calcitonin-gene-related peptide. In 14 patients the erectile response to the combination of calcitonin-gene-related peptide and prostaglandin E1 was compared to the response of prostaglandin E1 alone, and with a combination of 15mg./ml. papaverine and 0.5mg./ml. phentolamine.Calcitonin-gene-related peptide induced an increase in the penile arterial inflow, cavernous smooth muscle relaxation and cavernous outflow occlusion. Histochemical results indicated nerve fibers positive for calcitonin-gene-related peptide within the cavernous bodies. A dose-dependent erectile response to calcitonin-gene-related peptide was observed at doses of 500ng. to 25μg. Systemic side effects were first observed at a dose of 25μg. in 2 of 7 patients. The combination of calcitonin-gene-related peptide and prostaglandin E1 was more effective in inducing a full erection than either prostaglandin E1 alone or the combination of papaverine and phentolamine. Pain was reported in 4% of the patients who received the combination of calcitonin-gene-related peptide and prostaglandin E1, whereas 42% of those who received prostaglandin E1 alone reported pain. Our results suggest that calcitonin-gene-related peptide may be a possible neurotransmitter for penile erection. A combination of calcitonin-gene-related peptide and prostaglandin E1 seems to be an effective alternative combination in the treatment of impotence.

Effect of Apomorphine on Penile Tumescence in Men with Psychogenic Impotence

AbstractIn a double-blind study using physiological recording of penile tumescence, brachial subcutaneous apomorphine hydrochloride injections elicited penile erections in men with psychogenic impotence. This observation is compatible with the hypothesis of central dopaminergic involvement in human penile erection. Since apomorphine is believed to induce erections by its effect on brain monoamine pathways, apomorphine response may have diagnostic use in evaluating the etiology of erectile failure.