Author(s): Guiliano F, Rampin O, Benoit G, Jardin A
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Abstract The peripheral control of local mechanisms of erection and detumescence has now been more clearly elucidated. This knowledge has been acquired as a result of the recent development of pharmacological research designed to study the regulation of erectile smooth muscle tone. Smooth muscle fibres of the corpora cavernosa and arteries supplying the penis relax in response to a reduction of intracellular calcium. This relaxation allows both an increase of the blood flow to the penis and opening of sinusoid spaces. Cyclic nucleotides, cAMP and cGMP, are intracellular messengers of the mediators acting on smooth muscle fibres and regulating these intracellular calcium movements. Gap-junctions, greatly facilitating rapid ion exchanges between smooth muscle fibres, make erectile tissue a real functional syncytium. Nonadrenergic, noncholinergic neurotransmitters, mainly nitric oxide (NO), are synthesized by parasympathetic neurons present in cavernous nerves and act directly on smooth muscle fibres. NO increases the intracellular cGMP concentration. Other proerectile mediators, such as acetylcholine, CGRP or substance P, act via endothelial cells by promoting the synthesis and release of NO by these cells. In contrast, neurotransmitters of the sympathetic nervous system, norepinephrine and neuropeptide Y, and endothelin, secreted by endothelial tissues, induce contraction of cavernous smooth muscle fibres, thereby opposing erection. Oxygenation of the cavernous tissue is also an important factor in the regulation of local mechanisms of erection. Poor oxygenation prevents the synthesis of cGMP and predisposes to cavernous fibrosis due to increased synthesis of collagen via TGF beta. A better understanding of the peripheral pharmacology of erection opens the way to new pathophysiological and therapeutic prospects in the broad symptomatic context of erectile dysfunction.
This article was published in Prog Urol
and referenced in Reproductive System & Sexual Disorders: Current Research