Angiotensin II Increases Corpus Cavernosal Contractility and Oxidative Stress in Partial Bladder Outlet Obstructed Rabbits: Relevance to Erectile Dysfunction

Abstract

Introduction We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells. Aim To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO. Methods Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ bath studies determined Ang II/NO interaction on CCSM function using losartan (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role of OS in the Ang II response was also determined using diphenylene iodonium chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, which inhibits superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide). Main Outcome Measure Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM function. Results Ang II caused a dose-dependent contraction of CCSM strips that was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil and losartan. Conclusions These findings imply that the increased Ang II contractile response is a pathological consequence of PBOO and that AT1 receptor inhibition may be a therapeutic approach to treat ED associated with PBOO.

Effects of silodosin, a selective alpha‐1A adrenoceptor antagonist, on erectile function in a rat model of partial bladder outlet obstruction

“…Constant compression on the cavernosal nerves by the urethral ligature might diminish nitrergic innervation in CC, and cause hypoxia and ischemia. In a previous study, PBOO induced oxidative stress and reduced the ICP . In the Goi's study, silodosin decreased markers of oxidative stress .…”

“…In a previous study, PBOO induced oxidative stress and reduced the ICP. 20 In the Goi's study, silodosin decreased markers of oxidative stress. 12 On the other hand, a 1A -AR activates C-fiber afferents in a rat model of cerebral infarction.…”

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

“…In anesthetized dogs, intracavernous injection of Ang II caused termination of spontaneous erection, whereas administration of losartan resulted in smooth muscle relaxation and erection [27]. Also, in human corpus cavernous smooth muscle strips, administration of losartan mediated corpus cavernous smooth muscle relaxation [28]. In addition, the concentration of Ang II was found to be significantly increased in cavernosal tissue in a diabetic rat model, and to markedly reduce the erectile response [29].…”