Neurotransmission and the contraction and relaxation of penile erectile tissues

Abstract

The balance between contractant and relaxant factors controls the smooth muscle of the corpus cavernosum and determines the functional state of the penis (detumescence and flaccidity versus tumescence and erection). Noradrenaline contracts both the corpus cavernosum and penile vessels, mainly via stimulation of alpha(1)-adrenoceptors. Recent investigations have demonstrated the presence of several subtypes of alpha 1-adrenoceptors (alpha(1A), alpha(1B), and alpha(1D)) in the human corpus cavernosum and also that the noradrenaline-induced contraction in this tissue is probably mediated by two or, possibly, three receptor subtypes. Even if much of the available in vitro information suggests that endothelins (ETs) may be of importance for mechanisms of detumescence and flaccidity, the role of the peptides in the control of penile smooth-muscle tone in vivo is unclear, as is the question as to whether they can contribute to erectile dysfunction. For further evaluation of the clinical importance of ETs in penile physiology and pathophysiology, clinical studies on ET-receptor antagonists would be of interest. Neurogenic nitric oxide (NO) has been considered the most important factor for relaxation of penile vessels and the corpus cavernosum, but recent studies in mice lacking neurogenic NO synthase (NOS) have shown these animals to have normal erections. This focuses interest on the role of endothelial NOS and on other agents released from nerves or endothelium. For the time being the most effective means of inducing penile erection in men involves the intracavernous administration of prostaglandin E1 (PGE1). PGE1 may act partly by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP). Recent results obtained with the adenylate cyclase stimulator forskolin suggest that penile smooth-muscle relaxation leading to penile erection can be achieved through the cAMP pathway. Thus, transmitters and agents acting through this second-messenger system may significantly contribute to relaxation of penile smooth muscle and to erection.

Nocturnal penile tumescence and rigidity (NPTR) findings in spinal cord injured men with erectile dysfunction

“…For a long time, the cerebrospinal pathway projecting on the sacral erection centre was considered to mediate solely psychogenic as well as nocturnal erections. If we assume that in SCI patients with completely destroyed reflexogenic sacral erection centre (S2-S4), their thoracolumbar sympathetic erection centre (T10-L2) is not only responsible for detumescence (via adrenergic transmitters 19,20 ), but also becomes a proerectile function (via a still unknown pathway), then our results underline the theory of a sympathetic dichotomy, which was already described by other authors in animal models and from clinical observations in SCI patients. [21][22][23][24][25] Accordingly, our SCI patients with destroyed sacral conus and preserved thoracolumbar metameres were still able to get erections after audiovisual stimulation; direct tactile stimulation of the glans penis never resulted in erections in these cases.…”

Non‐surgical management of erectile dysfunction

“…The mechanism of nocturnal erections occurring during REM sleep is unknown, but they are more sensitive to low androgen levels than psychogenic or re¯exogenic erections. The local release of a large number of peptides and catecholamines (Stief et al, 1990;Crowe et al, 1991;Gerstenberg et al, 1992;Rajfer et al, 1992;Martinez-Pineiro et al, 1993) including endothelial nitric oxide synthase (Andersson & Stief, 1997) and, recently, carbon monoxide (Burnett et al, 1998) have been implicated in the erectile response.…”

Evaluation of oral Ro70-0004/003, an α1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction

“…It has been established that a 1 , but not a 2 , adrenoceptors mediate contraction of human erectile tissue. 6,7 Molecular and pharmacological studies have indicated the existence of at least three a 1 -adrenoceptor subtypes (a 1A , a 1B and a 1D ). Although human corpus cavernosal tissue is endowed with a 1A -adrenoceptors, 10 functional evidence for their involvement in contractile responses is lacking.…”

“…It has been suggested that the etiology of MED may be related to impaired corpus cavernosal relaxation andaor heightened corpus cavernosal contractile tone. 7 Sildena®l potentiates NO-mediated cyclic guanosine monophosphate (cGMP)-induced relaxation of corpus cavernosum. 4,7 The erectile process can also be facilitated by antagonizing NE-induced, a 1 -adrenoceptor mediated contraction of corpus cavernosum.…”

“…7 Sildena®l potentiates NO-mediated cyclic guanosine monophosphate (cGMP)-induced relaxation of corpus cavernosum. 4,7 The erectile process can also be facilitated by antagonizing NE-induced, a 1 -adrenoceptor mediated contraction of corpus cavernosum. 8 Clinically, non-selective a-adrenoceptor antagonists such as phentolamine have been used for the treatment of MED.…”