Regulation of tone in penile cavernous smooth muscle

Abstract

Since Benson, in 1983, reported on a potent nonadrenergic, noncholinergic (NANC) transmitter postulated to relax penile vessels and the corpus cavernosum, much new information on the mechanisms of contraction and relaxation of corporeal smooth muscle and penile vasculature has been obtained. The information currently available suggests that NANC transmitters may be involved in both contractile and relaxant responses of penile erectile tissues. There is good experimental evidence to allow the assumption that neurogenic nitric oxide (NO) is a mediator of penile erection, but even if NO probably is the most important factor for relaxation of penile vessels and the corpus cavernosum, this does not exclude the possibility that other agents released from nerves m a y have a modulatory function in this process. However, the roles of, for example, vasoactive intestinal polypeptide and related peptides as neurotransmitters and/or neuromodulators in the nervous control of penile erection have yet to be established. The restricted availability of human penile erectile tissues has led to the use of cavernous tissue and penile vessels from animals, both for screening and for detailed analysis of mechanisms previously demonstrated to exist also in human tissues. When interpreting the results obtained, it is important to stress that there may be important differences between human and animal tissues, that each of the tissues only gives a piece of information on the complex process of penile erection, and that the physiological and clinical importance of results from such experiments may be limited. The differing responses in different parts of the vasculature within the penis and the multiplicity of putative transmitters present in the corpus cavernosum and in perivascular nerves make further investigations necessary, as do the interactions between transmitters and neuromodulators at the neuromuscular junction, and between the neural and endothelial control of vascular tone. matter has increased markedly, mainly as a consequence of the now widely used principle of treating impotence by intracavernous injections of vasoactive agents. To fulfill better the needs of each individual patient and to treat impotence on the basis of the underlying pathological disorder, it is essential to gain detailed knowledge about the mechanisms controlling tumescence and detumescence under normal conditions and to characterize the possible factors influencing this finely tuned system.It has long been believed that the contraction of penile smooth muscle, necessary for keeping the penis in the flaccid state, is maintained mainly, but probably not solely, by the release of noradrenaline acting on postjunctional o~adrenoceptors, and several reviews discussing this issue have recently been published (e.g., [7, 8, 51,121]). It is also known that parasympathetic activity is of importance for penile erection, possibly through release of factors causing inhibition and thereby decreasing the effects of contractile factors. However, because of the quite var...

Effects of short-term moderate exercise training on sexual function in male patients with chronic stable heart failure

“…By inhibiting the breakdown of cyclic-GMP, nitric oxide released by endothelial cells continues to activate guanylate cyclase enzyme causing smooth muscle relaxation in the corpus cavernosum and sustained vasodilation of the cavernosal and helicine arteries [20,21]. The consequence is elongation and compression of the subtunical venules, producing penile erection as a balance between the perfusion pressure in the cavernosal artery and the resistance to outflow through the compressed venules [38]. Recently, sildenafil has been studied in 23 men with stable congestive heart failure, with promising results in terms of erectile dysfunction attenuation and functional capacity improvement [22].…”

Intracavernous pharmacotherapy

“…It stimulates adenylate cyclase and the formation of cyclic AMP [27]. Basic research suggests that VIP may be a neurotransmitter or co-transmitter in the cavernous tissue of different species [5]. VIP was shown not to be capable of inducing rigid erections when injected intracavernously, even at very high doses [104].…”

“…Phenoxybenzamine induces a long-lasting erection by a firm and irreversible binding to alpha1-and alpha2-adrenergic receptors. It is therefore an extremely priapismogenic drug when injected intracavernously [4][5][6]14]. Phentolamine is a nonspecific alpha-receptor-blocking agent with a very short plasma half-life (3-5 min) and does not cause a satisfactory erectile response per se.…”

Signal transduction in cavernous smooth muscle

“…Only a few years later, broad coverage of erectile neurotransmission [1,2], especially that involving the NO pathway [12,13,15], was obtained. Derived from these new insights, more physiological pharmacological therapies could be offered to patients with erectile dysfunction [2,24].…”