Induced Penile Erection Research Articles

Efficiency and Side Effects of Prostaglandin El in the Treatment of Erectile Dysfunction

The efficiency and side effects of a single dose of intracorporeally applied prostaglandin El (20mcg.) in inducing penile erection were examined. In addition, the effect of this dose of prostaglandin El was compared to the effect of 7.5mg. papaverine plus 0.25mg. phentolamine in a double-blind, crossover designed study. We tested twice 12 men 52.9 ± 7.6 years old (mean ± standard deviation) with erectile dysfunction. On 1 occasion the subjects received 20mcg. prostaglandin El and on the other they received 7.5mg. papaverine and 0.25mg. phentolamine. At this dosage prostaglandin El was most effective in inducing artificial penile erection (11 of 12 patients). However, 75 per cent of the subjects reported burning sensations during the entire period of erection and in 1 prostaglandin El treatment resulted in a sustained erection. At the doses used, prostaglandin El was more effective in inducing penile erection than papaverine plus phentolamine (11 versus 6 patients). Intracavernous injection of prostaglandin El is a potent tool for artificial penile erection and warrants precise examination for its potential clinical use.

The Role of Vasoactive Intestinal Polypeptide as a Neurotransmitter in Canine Penile Erection: A Combined in Vivo and Immunohistochemical Study

Vasoactive intestinal polypeptide (VIP), a 28-amino-acid polypeptide found in the human gut and genitourinary tract, primarily affects vasodilation and smooth-muscle relaxation. These effects have led to speculation that this neuropeptide may be a neurotransmitter in certain bodily functions, such as penile erection. We therefore designed an in vivo animal model to elucidate the influence of VIP and VIP antibody on the different stages of penile erection. We also performed immunohistochemical studies of the penile tissue to obtain further information about the distribution of VIP in the corpora cavernosa.Intracavernous injection of VIP induced penile erection. Its effect on arterial inflow was minor, but it caused active venous outflow restriction and was important in maintaining erection. VIP antibody blocked venous outflow restriction during neurostimulation-induced erection. VIP was found in the cavernous tissue (in the area between the smooth-muscle cells and the sinusoidal spaces) in close proximity to the arteries.We conclude that VIP is a neurotransmitter in the erectile tissue of the penis, and that its effects are similar to those from electrostimulation of the cavernous nerve. VIP increases arterial flow, decreases venous flow, and induces sinusoidal relaxation.

Assessment of the Immediate and Long-Term Effects of Pharmacologically Induced Penile Erections in the Treatment of Psychogenic and Organic Impotence

Thirty-eight patients with predominantly organic and 29 with psychogenic impotence had intracavernosal injections of a combination of 30 mg papaverine and 1 mg phentolamine on at least one occasion. An immediate increase in length and penile rigidity resulted in all subjects. Eighteen of the organic patients subsequently developed spontaneous erections for periods ranging from 1 week to 1 month. Nineteen of the 24 patients in the psychogenic group had spontaneous erections, five for at least 4 months and 14 for 2 to 8 weeks. Increasing the dose was of benefit only to organic patients who initially had a poor response. Three of eight patients with a poor immediate response to pharmacologically induced penile erections (PIPE) were found to have venous incompetence. PIPE is therefore of value in the diagnosis and treatment of organic and psychogenic impotence.

Apomorphine-induced penile erection and yawning: site of action in brain

Microinjection of the dopamine (DA) agonist apomorphine into the paraventricular nucleus of the hypothalamus (PVN) induced penile erection and yawning in rats. A significant effect was elicited by a dose of apomorphine as low as 5 ng. The symptomatology usually began within 5 min after the microinjection, lasted for 30–50 min, and was identical to that induced by the systemic administration of the drug. Stereotypy and hypermotility were nerve observed after apomorphine microinjection into the PVN, even at the highest dose tested (1 μg). Microinjections of the same doses of apomorphine into the hypothalamic ventromedial and dorsomedial nucleus, preoptic area, caudate nucleus, nucleus accumbens and substantia and substantia nigra, were ineffective. LY 171555, a specific D 2 DA receptor agonist, and (+)-3-PPP, but not (−)-3-PPP nor the specific D 1 DA receptor agonist SKF 38393, were as effective as apomorphine when injected into the PVN. Apomorphine-induced penile erection and yawning were antagonized by pretreatment with neuroleptic drugs, such as haloperidol, (−)-sulpiride, a specific D 2 DA antagonist, and SCH 23390, a specific D 1 DA antagonist. The present results suggest that the PVN is the brain area where D 2 DA agonists act to induce penile erection and yawning. Moreover, since the PVN contains the cell bodies of a group of incertohypothalamic DA neurons, the above results suggest for the first time a possible involvement of the incerto-hypothalamic DA system in the expression of penile erection and yawning.

Studies on Intracavernosal VIP Levels during Pharmacologically Induced Penile Erections

Intracavernosal and peripheral venous vasoactive intestinal polypeptide (VIP) levels were measured in men with predominantly organic or predominantly psychogenic impotence. The measurements were taken at intervals up to 30 min following intracavernosal injections of saline, papaverine hydrochloride and papaverine hydrochloride and phentolamine. Levels were also measured after tactile and visual sexual stimulation and following an intravenous injection of papaverine and phentolamine. A penile erection occurred in all men receiving intracavernosal vasoactive compounds. The mean VIP concentration did not alter significantly in either cavernosal or peripheral venous blood during the erection. Mean VIP concentrations were significantly greater in the neurogenic (all diabetic) group than in the other groups studied. Mean cavernosal and peripheral VIP concentrations did not alter following tactile or visual sexual stimulation and no significant alteration in mean peripheral venous VIP concentration occurred following injection of papaverine and phentolamine. The putative role of VIP in the induction of penile erection has not been elucidated in these studies.

Drug-induced penile erections in rats: indications of serotonin 1B receptor mediation

The induction of penile erections by a variety of compounds with a direct or indirect effect on serotonin (5HT) receptors was investigated in rats. L-5-Hydroxy-tryptophan (L-5HTP) induced penile erections when co-administered penile erections is within the central nervous system. Penile erections were also induced by the 5HT uptake inhibitors zimelidine, fluoxetine, citalopram, Org 6997, by the 5HT-releasing agent fenfluramine and by the putative 5-HT 1B receptor agonist 1-(3′-chlorophenyl)-piperazine (mCPP). The 5HT 1A-agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) did not induce penile erections. The less selective 5HT receptor agonists 5-methoxy-N,N-dimethyl-tryptamine (5MeODMT), 5-methoxytryptamine (5MeOT), dl-lysergic acid diethylamide (LSD) and Ru 24969 were also ineffective. Induction of penile erections by quipazine appeared only when this compound was co-administered with the 5HT 2 receptor antagonist pirenperone. Receptor antagonists were tested against penile erections induced by Org 6997. The β-adrenoceptor antagonists that also have 5HT 1 antagonistic properties, (S)-pindolol and dl-propranolol, antagonized Org 6997-induced penile erections but butoxamine and metoprolol did not. Spiperone and pirenperone in doses selective for 5HT 1A and 5HT 2 receptors respectively were also inactive. Haloperidol, 0.46 mg/kg, partially attenuated penile erections induction. The data are discussed in the light of the hypothesis that penile erections induction by serotonin-mimetic compounds is mediated by 5HT 1B receptors in the striatum.

Monosodium glutamate does not alter ACTH- or apomorphine-induced penile erection and yawning

The effect of the intracerebroventricular (ICV) injection of ACTH 1–24 (1, 5 and 10 ωg) or the subcutaneous administration ofv apomorphine (20 and 80 ωg/kg SC) on spontaneous penile erection and yawning was studied in rats treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic ACTH, α-MSH and endorphin-like peptides. Neonatal MSG treatment failed to antagonize either apomorphine- or ACTH-induced yawning in male and female rats, or to alter the number of penile erection episodes induced by the two substances in male rats. In contrast, hypophysectomy, that does not alter the concentration of hypothalamic ACTH and α-MSH, caused a marked prevention of apomorphine- and ACTH-induced responses, in agreement with previous studies. The results suggest that the integrity of opiomelanotropinergic neurons in the hypothalamus is not necessary for the induction of yawning and penile erection by ACTH-derived peptides, and that apomorphine and other dopamine agonists apparently do not induced penile erection and yawning by releasing an ACTH-derived peptide in brain.

Assessment of the immediate and long-term effects of pharmacologically induced penile erections in the treatment of psychogenic and organic impotence.

Thirty-eight patients with predominantly organic and 29 with psychogenic impotence had intracavernosal injections of a combination of 30 mg papaverine and 1 mg phentolamine on at least one occasion. An immediate increase in length and penile rigidity resulted in all subjects. Eighteen of the organic patients subsequently developed spontaneous erections for periods ranging from 1 week to 1 month. Nineteen of the 24 patients in the psychogenic group had spontaneous erections, five for at least 4 months and 14 for 2 to 8 weeks. Increasing the dose was of benefit only to organic patients who initially had a poor response. Three of eight patients with a poor immediate response to pharmacologically induced penile erections (PIPE) were found to have venous incompetence. PIPE is therefore of value in the diagnosis and treatment of organic and psychogenic impotence.

Oxytocin-induced penile erection and yawning: Site of action in the brain

Microinjection of oxytocin into the paraventricular nucleus of the hypothalamus or into the CA1 field of the hippocampus induced a dose-dependent increase in the number of penile erection and yawning episodes in male rats. The minimal effective dose of oxytocin injected into the paraventricular nucleus was 3 ng. This dose induced the above-mentioned behaviors in 60% of the treated rats. Doses of 9 ng or higher induced the symptomatology in more than 85% of the animals. On the other hand, when the peptide was injected into the CA1 field of the hippocampus, 9 ng bilaterally were necessary to elicit penile erection and yawning in 62% of the rats. Arg8-vasopressin, which only differs from oxytocin in two amino acids, induced penile erection and yawning when injected either into the paraventricular nucleus or into the hippocampus, but was 5-10 times less potent than oxytocin. Oxytocin injection into the lateral septum, caudate nucleus, subiculum, preoptic area, ventromedial nucleus and supraoptic nucleus, was ineffective. The powerful effect of oxytocin on the induction of yawning and penile erection, suggests a physiological role of hypothalamic and hippocampal oxytocin in the regulation of such responses.

Antagonism of drug-induced yawning and penile erections in rats

A number of centrally active drugs were tested for antagonism of physostigmine- or apomorphine-induced yawning and for apomorphine-induced penile erections. The α 2-adrenoceptor antagonists piperoxan and idazoxan inhibited the yawning response without affecting the penile erections. The 5HT agonist quipazine and the histamine antagonist dexchlorpheniramine inhibited the yawning response more effectively than the penile erections. Dexchlorpheniramine even enhanced the apomorphine-induced penile erections and induced penile erections in physostigmine-treated rats. The 5HT antagonists metergoline and methysergide blocked the apomorphine-induced penile erections without affecting the yawning response. The α 2-adrenoceptor agonist clonidine, the dopamine antagonist sulpiride, the antihistaminic mepyramine and the benzodiazepine chlordiazepoxide inhibited both yawning and penile erections at the same dose level. The α 1-adrenoceptor antagonists prazosin and phenoxybenzamine were inactive. It is concluded the yawning and penile erections can be differentially affected by drug treatments. Also, while concomitant yawning and penile erections can be selectively induced by a class of dopamine receptor agonists, the same selectivity does not apply to antagonism of these induced behaviours.

Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide.

The haemodynamics of erection were elucidated in the anaesthetized dog by analysing in quantitative terms the changes of penile arterial inflow, venous outflow and tissue volume during graded pelvic nerve stimulation. The study also provides information on possible neurotransmitter mechanisms of the erectile response. Erection evoked by pelvic nerve stimulation appeared to result from two main circulatory events: first, there was a prompt dilatation of the penile 'resistance vessels', causing a greatly increased arterial inflow which in the early phase bypassed the cavernous bodies and, hence, increased venous outflow to the same extent. Secondly, the erectile response proper began after a distinct delay (approximately equal to 20 s). This was apparently caused by sudden opening of low resistance 'shunt vessels' diverting part of the arterial inflow into the cavernous bodies, leading to rapid filling. During the filling phase arterial inflow greatly exceeded venous outflow, and returned to the venous outflow level again in the steady state of full erection. The initial dilator response seemed to ensure rapid erection by establishing a high pressure head from the arterial microvessels to the cavernous spaces. The threshold frequency for the penile vasodilator response to pelvic nerve stimulation was 1-2 Hz and was always higher for the erectile volume response, viz. 2-4 Hz. Maximal effects for both were obtained at 16 Hz, causing on the average a 25-fold increase in peak arterial inflow, a 17-fold increase in venous outflow and a 107% increase in penile volume. Muscarinic blockade by atropine caused no significant decrease in the blood flow response induced by pelvic nerve stimulation, but clearly curtailed the erectile response. This indicates that the dilatation of the penile 'resistance vessels' is mainly non-cholinergic in nature, whereas a cholinergic mechanism seems to contribute to the erectile volume response proper. Pelvic nerve stimulation caused a substantial output of vasoactive intestinal polypeptide (VIP) from the penis which was correlated in onset and duration to the vasodilator response. Intra-arterial (I.A.) infusion of VIP elicited moderate erection and a penile vasodilator response which resembled the neural response. Similar effects were evoked by I.A. infusion of substance P, but the output of this peptide from the penis during stimulation was poorly correlated to the vascular events. These in vivo observations indicate that VIP might be the neurotransmitter responsible for the non-cholinergic pelvic nerve induced penile vasodilatation.

Localisation and measurement of VIP in the genitourinary system of man and animals

VIP is present in the genitourinary system of man and animals. In man the highest concentrations are found in the penis, the uterus and vagina and in the urinary bladder. VIP nerves heavily innervate the erectile tissue of the male external genitalia, the uterine smooth muscle and blood vessels, the seromucous glands of the cervix, and the lamina propria and vaginal epithelium. In the urinary bladder, VIP nerves are located beneath the transitional epithelium, in the lamina propria and in the smooth muscle. Other areas well innervated by VIP nerves include the prostate, seminal vesicles and vasa deferentia. Chemical (phenol- and 6-OHDA) or surgical (hypogastric or pelvic nerve section) extrinsic denervation fail to deplete the genitourinary system of its VIP content, supporting the view that VIP-containing nerves originate from local ganglion cells. Indeed, neuronal cell bodies containing VIP are seen in the paracervical ganglia of the female genitalia, the para- or intramural bladder ganglia and scattered through the base of the cavernosum body, the neck of the bladder and the prostate. The finding of elevated levels of VIP in the local circulation after induced penile erection in man and mammals and the ability of VIP to relax the detrusor muscle of the bladder suggests that the peptide may be involved in penile erection and bladder relaxation, as does the marked VIP depletion in the penis or bladder in patients suffering from diabetic impotence or bladder instability.

Neuroanatomy of Penile Erection: Its Relevance to Iatrogenic Impotence

The neuroanatomy of erection in men is not well defined. Recently, we isolated successfully the cavernous nerves for acute and chronic neurostimulation to induce penile erection in dogs and monkeys. We then investigated the anatomy of these nerves in humans by cadaveric dissection and serial histologic sectioning. Our experience in tracing the spinal nuclei responsible for vesical and urethral function by transportation of horseradish peroxidase enabled us to explore the location and organi;ation of the spinal center for erection. Thus, systemic knowledge of the neuroanatomy of erection was accumulated. The spinal nuclei for control of erection are located in the intermediolateral gray matter at the Sl to S3 and Tl2 to L3 levels in dogs, and the S2 to S4 and TlO to L2 levels in humans. From these sacral nuclei axons issue ventrally and join the axons of the nuclei for the bladder and rectum to form the sacral visceral efferent fibers. These fibers emerge from the anterior root of S2 to S4, and join the sympathetic fibers to form the pelvic plexus, which then branches out to innervate the bladder, rectum and penis. The fibers innervating the penis (cavernous nerves) travel along the posterolateral aspect of the seminal vesicle and prostate, and then accompany the membranous urethra through the genitourinary diaphragm. These fibers are located on the lateral aspect of the membranous urethra and ascend gradually to the 1 and 11 o’clock positions in the proximal bulbous urethra. Some of the fibers penetrate the tunica albuginea of the corpus spongiosum, while others spread to the trifurcation of the terminal internal pudendal artery and innervate the dorsal, deep and urethral arteries. Shortly before the 2 corpora cavernosa merge the cavernous nerves penetrate the tunica albuginea along with the deep artery and cavernous vein. The terminal branches of these nerves innervate the helicine arteries and the erectile tissue within the corpora cavernosa. Because of the intimate relationship of the cavernous nerves to the rectum, prostate and urethra, they can be damaged easily during urological and pelvic procedures.This systemic knowledge of the human cavernous nerves from the spinal center to the erectile tissue should permit a better understanding of erection and impotence. Furthermore, with the aid of intraoperative neurostimulation, the cavernous nerves may be identified and preserved, thereby preventing iatrogenic impotence.

Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects

1. Apomorphine HC1 (Apo) (0.25 0.5 or 0.75 mg sc), a dopamine (DA) receptor agonist, induced penile erections (PEs) (monitored by mercury strain gauges and continuous recording on paper strip charts) in 7 out of 9 normal subjects and placebo in 1 of these 9 (p < 0.05). 2. Apo-induced PEs recurred in each of the 6 subjects retested. 3. Benztropine (2 mg iv) had no effect on Apo-induced penile tumescence (PT). 4. These data suggest (a) DA mechanisms play a role in normal erectile function (b) DA-mediated PT is not modulated by cholinergic systems (c) evaluation of the erectile response to Apo may provide a simple ancillary test to the investigation of impotence and a way of identifying a subpopulation of impotent subjects with impaired DA function who may respond to long-acting DA agents (d) Apo-induced PT may provide a novel way of studying DA function in man.

Penile erections induced by amantadine in male rats

Amantadine induces repeated episodes of penile erection and ejaculation in intact but not in castrated adult male rats. Testosterone propionate administered to castrated rats restores their responsiveness to the sexual stimulant effect of amantadine. Atropine, but not atropine methyl bromide, prevents amantadine induced penile erection.

Yawning and penile erection induced in rats by cortical spreading depression.

BEHAVIOUR can be stimulated as well as disrupted by cortical spreading depression (CSD)—the massive wave of neural depolarization and subsequent EEG depression which can be induced to spread slowly over a cortical hemisphere by injection of KCl. Eating, drinking and locomotor behaviour have been elicited in rats by administering single waves of CSD (ref. 1). Consummatory behaviour was most likely to be elicited if an animal had extensive feeding experience in the testing chamber. I wish to describe two further effects of single waves of CSD, the induction of penile erections and of stretching and yawning responses.