Roles of attenuated neuronal nitric‐oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits

Abstract

RESULTSThe neurogenic relaxation and cGMP production in response to electrical-field stimulation were significantly impaired in aged cavernosal specimens. Western blot analysis showed that nNOS protein was highly expressed in cavernosal specimens from young rabbits, but was undetectable or greatly decreased in old rabbits, with no change in overall NOS activity. Arginase activity in aged cavernosal specimens was significantly higher than in young rabbits. Supplementing with excess L -arginine, or giving S-(2-boronoethyl)-L -cysteine as an arginase inhibitor, significantly increased the neurogenic relaxation at lower frequencies only in the younger rabbits. CONCLUSIONThese results suggest that impairment of neurogenic and NO-mediated relaxation in the aged corpus cavernosum possibly results from the down-regulation of nNOS protein. The reduced L -arginine bioavailability to nNOS due to accelerated arginase activity would lead to further impairment of neurogenic NO production, in concert with decreased nNOS protein expression. KEYWORDSneuronal nitric oxide synthase, arginase, erectile dysfunction, ageing OBJECTIVETo investigate whether changes in neuronal nitric oxide synthase (nNOS) protein expression and arginase activity are implicated in impairing the neurogenic cavernosal relaxation in aged rabbits, as NO is important in the neurogenic relaxation of corpus cavernosum during the erectile state. MATERIALS AND METHODSCavernosal specimens of young adult (3-6 months old) and aged (36-48 months old) rabbits were used for isometric tension experiments, Western blot analysis, cGMP determination and measurements of NOS and arginase activities.

A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing

“…Consistently, it is known that NO synthase activity undergoes reduction with increasing age (Valdez et al 2004;Numao et al 2007). Interestingly, NO synthase also occurs in the inner mitochondrial membrane, functioning as a regulatory factor of respiration (Kato and Giulivi 2006), and reduced mitochondrial inner membrane as well as decreased expression of some respiratory enzymes have been found in GM-fed mice.…”

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Other contributing factors could be the presence of endogenous NOS inhibitors (e.g., asymmetric dimethylarginine) and an up-regulation of arginase activity. High levels of asymmetric dimethylarginine have been demonstrated in multiple disorders in which NOS dysfunction has been implicated, including several of the disorders mentioned in the sections that follow, and increased arginase activity has been demonstrated in CC tissue in, for example, diabetes, aging, and smoking (Bivalacqua et al, 2001b;Imamura et al, 2007;Numao et al, 2007).…”

Possible Involvement of Altered Arginase Activity, Arginase Type I and Type II Expressions, and Nitric Oxide Production in Occurrence of Intimal Hyperplasia in Premenopausal Human Uterine Arteries

“…It has been reported that the enhanced arginase activity decreases L-arginine availability to NOS, thus impairing NO production (17). Enhanced arginase activity has been implicated in a number of conditions characterized by vascular dysfunction including pulmonary hypertension (18), intimal hyperplasia (19), agingassociated vascular dysfunction (20,21), and smokingrelated vascular dysfunction (22).…”