Effect of angiotensin II on corpus cavernosum smooth muscle in relation to nitric oxide environment: in vitro studies in canines

Abstract

In extracavernosal vascular tissue, smooth muscle tone is modulated by a balance between angiotensin II (Ang II) and nitric oxide (NO). We hypothesized that these substances also play an important role in regulating cavernosal smooth muscle contractility. We therefore studied the in vitro effects of an Ang II receptor antagonist and a nitric oxide synthase (NOS) inhibitor on the contractile effects of Ang II, phenylephrine, and electrical ®eld stimulation in canine corpus cavernosum. Ang II caused a dose-dependent contraction of cavernosal smooth muscle which was inhibited by the Ang II receptor antagonist and augmented by NOS inhibition. Contractions induced by phenylephrine or electrical stimulation were diminished by the Ang II receptor antagonist, and augmented by NOS inhibition. We conclude that Ang II plays an important role in modulating cavernosal smooth muscle tone, and that the contractile effect of Ang II on cavernosal tissue is modulated by the local NO environment.

Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with erectile dysfunction

“…In cavernosal tissues, a balance between ANG II and NO modulates smooth muscle tone, thereby regulating regional blood¯ow. 6 These vasoactive substances mediate opposing actions, with NO causing a decrease and Ang II mediating an increase in smooth muscle tone. Unlike in the case of the ACE gene polymorphism, we failed to detect any signi®cant associations between the ecNOS genotype and erectile dysfunction.…”

“…2,5 RAS has cross-talk with NO-cyclic GMP pathway for erection in the cavernosal smooth muscle. 6 The angiotensin converting enzyme (ACE) gene (encoding kininase II) contains a polymorphism based on the presence (insertion [I]) or absence (deletion [D] within an intron of a 287-base-pair ( bp) nonsense DNA domain, resulting in three genotypes (DD and II homozygotes, and ID heterozygotes). An insertiona deletion (IaD) polymorphism for the gene that encodes the ACE is associated with variation of circulating level of ACE.…”

Association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and erectile dysfunction in patients with metabolic syndrome

“…In vitro, angiotensin II contracted human and canine corpus cavernosum smooth muscle. 10,25 Elevated levels of angiotensin II have been noted in the systemic and cavernous blood of patients with organic ED, suggesting the role of this peptide in the pathogenesis of ED. 9 Intracavernosal injection of angiotensin II caused contraction and terminated spontaneous erections in anesthetized dogs, whereas administration of lasortan, selectively blocking angiotensin II receptors, resulted in smooth muscle relaxation and erection.…”

“…In this context, it is of interest to elucidate factors determining the increased risk of ED in patients with MS. One of such factors could be the status of the renin-angiotensinaldosterone system that has long been known to be an important regulator of blood pressure and renal electrolyte homeostasis, and this system has also been implicated in the pathological changes of organ damage in MS through modulation of gene expression, growth, fibrosis and inflammatory response. 7,8 During detumescence, there is an increase in the level of angiotensin II in cavernous blood and this agent contacted human and canine corpus cavernosum smooth muscle in vitro, 9,10 pointing to the role of the renin-angiotensin-aldosterone in the physiology of erection and pathophysiology of ED.…”

Cardiovascular drug use and the incidence of erectile dysfunction

“…Angiotensin II is produced by the corpus cavernosum and causes contraction of cavernosal smooth muscle. 14,15 On the other hand, angiotensin II receptor antagonist induces smooth muscle relaxation. Cavernosal smooth muscle tone is controlled by a balance between angiotensin II and nitric oxide, 15 and imbalance between them may induce ED.…”