Smooth muscle pathology and erectile dysfunction

Abstract

Penile erection is a vascular phenomenon that results from smooth muscle relaxation, arterial dilation and venous restriction. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction of smooth muscle cells has been demonstrated in relation with this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance. Chronic ischemia is, therefore, associated with fibrosis but also with nitric oxide (NO)-cyclic guanosine monophosphate. The sensitivity of the a-adrenoceptors on the smooth muscle cells increases with aging. All those modifications can explain the prevalence of erectile dysfunction with aging. Low oxygen tension in prostanoid production may also play a role in the mechanism of ischemia-induced cavernosal fibrosis; however, intracavernous injections of prostaglandin E 1 do not seem to modify the intracavernous structures by reducing muscular atrophy. The effects of androgen on libido and sexual behavior are well established, but their role in the human erectile mechanism remains unclear. Several studies performed on animals have demonstrated impacts directly on both the physiological function and the trabecular structure of the corpora cavernosa in rats, dogs and rabbits. However, in humans, no study seems to demonstrate a role of testosterone on muscular atrophy or penile neurologic control. Testosterone treatment alters the human behavior but not penile physiologic processes. Further studies are necessary to explain the real role of testosterone not only on the peripheral mechanism of erection but also on the central control.

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

“…This condition compromises the oxygenation of the organ and appears to downregulate local NO synthesis, a major neurotransmitter in erection (Wespes 2002).…”

“…The efficiency of this process strongly depends on the integrity of the trabecular SM as corpora expansion is related directly to its content and inversely to that of connective tissue (CT) (Luo et al 2007;Nehra et al 1996;Wespes et al 1991). In fact, cavernous SM cell loss or functional impairment is the etiological basis of erectile dysfunction (ED) in many patients, since muscular tonus regulates the stages of erection, which cannot be achieved by vascular mechanisms alone (Wespes 2002). Any condition that results in structural changes in the cavernous tissue, such as aging or androgen depletion, is a potential contributor to ED.…”

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

“…[2][3][4][5][6] It has been proved that penile erection depends highly on the relaxation of penile arteries and erectile tissue such as the corpus cavernosum smooth muscle. [7][8][9][10] Some drugs such as inhibitors of PDE 5 or other vasodilators, which can promote the relaxation of corpus cavernosum smooth muscle, can be potentially used to treat ED. [11][12][13][14][15][16][17][18][19] It has been shown that there are many Chinese traditional herbals that can enhance sexual activity.…”

Erectile tissue molecular alterations with aging—differential activation of the p42/44 MAP Kinase pathway

“…Besides the decrease in erectile responses, the progression of age affects the composition and organization of cavernosal structures, having an impact on penile hemodynamic status (Bakircioglu et al 2001;Calabrò et al 1996;Costa and Vendeira 2008;Lin et al 2001;Montorsi et al 2003;Moreland 2000;Wespes 2002). Variations in SMC content, integrity and function (Bakircioglu et al 2001;Wespes 2002), changes in cavernosal angioarchitecture (Costa and Vendeira 2008), increased trabecular deposition of collagen and decreased concentration of elastic fibers were reported with aging (Calabrò et al 1996;Lin et al 2001;Moreland 2000). These changes reduce the elasticity and compliance of the elderly penis, contributing to erectile failure (Montorsi et al 2003).…”

“…With the advancement of age, several modifications in the composition and organization of these components were reported and suggested to alter elderly erectile capability. Aged cavernosal tissue presents variations in SMC content and function (Bakircioglu et al 2001;Wespes 2002), changes in vascular angioarchitecture (Costa and Vendeira 2008), increase in collagen production , and degeneration of elastic fibers (Calabrò et al 1996). These modifications affect penile hemodynamics by impairing cavernosal SMC relaxation, reducing penile elasticity, compliance, and promoting fibrosis (Montorsi et al 2003;Moreland 2000;Siroky and Azadzoi 2003).…”