The effect of superoxide dismutase on nitric oxide‐mediated and electrical field‐stimulated diabetic rabbit cavernosal smooth muscle relaxation

Abstract

Objective To investigate the effect of superoxide dismutase (SOD, the enzyme that accelerates the breakdown of the superoxide anion, O 2 ± to H 2 O) on nitric oxide (NO)-mediated and electrical ®eld stimulated (EFS) relaxation in diabetic rabbit cavernosal smooth muscle. Materials and methods Diabetes was induced with alloxan (65 mg/kg) in six adult New Zealand White rabbits. After 6 months, cavernosal smooth muscle strips from age-matched controls and diabetic animals were mounted in organ baths. After precontraction with phenylephrine (10 mmol/L) in the presence of atropine (1 mmol/L), guanethidine (5 mmol/L) and indomethacin (10 mmol/L), relaxation responses to EFS (1±20 Hz), carbachol (10 x8 x10 x4 mol/L) and sodium nitroprusside (SNP, 10 x9 x10 x4 mol/L) were assessed in the presence and absence of SOD (100 IU/ mL). Results SNP-and carbachol-mediated (endotheliumindependent and -dependent, respectively) relaxations were impaired in the diabetic cavernosal smooth muscle strips compared with controls (concentration required for 50% inhibition, 1.4 mmol/L for diabetic and 0.75 mmol/L for control with SNP, and 44 mmol/L for diabetic and 0.4 mmol/L for control with carbachol). SOD signi®cantly enhanced both SNP-and carbachol-mediated diabetic cavernosal smooth muscle relaxations (both P<0.05). EFS-mediated relaxations were also signi®cantly (P<0.05) impaired in the diabetic cavernosal smooth muscle strips; these relaxations were also signi®cantly (P<0.05) enhanced by SOD. Conclusion NO-and EFS-mediated cavernosal smooth muscle relaxation is impaired in a rabbit model of diabetes but SOD signi®cantly reversed the impaired relaxation. Therefore, in diabetes, the generation of reactive oxygen species may play an important role in the development of erectile dysfunction.

Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis

“…Reactive oxygen species from non-enzymatic glycosylation and increased NADPH oxidase activity impair endothelial function in erectile tissue and quench NO. In turn, this causes a reduction in the bioavailability of NO and peroxinitrite formation by nitrosative stress, which is highly toxic and damaging to the erectile tissue [25][26][27].…”

A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats

“…14 In diabetes, the NO-mediated responses have been shown to be reduced in both human and animal studies. [15][16][17][18][19] This has been attributed either to decreased availability of NO 20 or to decreased NO production secondary to downregulation of eNOS/nNOS expression [21][22][23] or degeneration of nitrergic nerves. 5,7,24 The decreased availability and/or production of NO is now widely accepted to be the primary cause for the significant loss of erectile function in diabetic men.…”

Endothelial dysfunction in diabetic erectile dysfunction

“…SOD and the metal chelator trientine also improve relaxation of diabetic corpus cavernosum. 67,68 Overexpression of SOD in vivo by gene transfer to the diabetic rat penis reduces the increased superoxide anion levels and restores erectile function. 57 Moreover, FeTMPyP, a catalyst of peroxynitrite decomposition, which converts peroxynitrite to nitrate, partially corrects NOdependent diabetic autonomic neuropathy and vasculopathy in the corpus cavernosum from diabetic mice.…”