Upregulation of gp91phox subunit of NAD(P)H oxidase contributes to erectile dysfunction caused by long-term nitric oxide inhibition in rats: reversion by regular physical training.
OBJECTIVE
To test the hypothesis that glyco protein 91phox (gp91(phox)) subunit of nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase is a fundamental target for physical activity to ameliorate erectile dysfunction (ED). Vascular risk factors are reported to contribute to ED. Regular physical exercise prevents cardiovascular diseases by increasing nitric oxide (NO) production and/or decreasing NO inactivation.


METHODS
Male Wistar rats received the NO synthesis inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) for 4 weeks, after which animals were submitted to a run training program for another 4 weeks. Erectile functions were evaluated by in vitro cavernosal relaxations and intracavernous pressure measurements. Expressions of gp91(phox) subunit and neuronal nitric oxidase synthase in erectile tissue, as well as superoxide dismutase activity and nitrite/nitrate (NO(x)) levels were determined.


RESULTS
The in vitro acetylcholine- and electrical field stimulation-induced cavernosal relaxations, as well as the increases in intracavernous pressure were markedly reduced in sedentary rats treated with l-NAME. Run training significantly restored the impaired cavernosal relaxations. No alterations in the neuronal nitric oxidase synthase protein expression (and its variant penile neuronal nitric oxidase synthase) were detected. A reduction of NO(x) levels and superoxide dismutase activity was observed in l-NAME-treated animals, which was significantly reversed by physical training. Gene expression of subunit gp91(phox) was enhanced by approximately 2-fold in erectile tissue of l-NAME-treated rats, and that was restored to basal levels by run training.


CONCLUSIONS
Our study shows that ED seen after long-term l-NAME treatment is associated with gp91(phox) subunit upregulation and decreased NO bioavailability. Exercise training reverses the increased oxidative stress in NO-deficient rats, ameliorating the ED.
Claudino
Mário A
MA
Department of Pharmacology, University of Campinas, Campinas, São Paulo, Brazil.
Franco-Penteado
Carla F
CF
Priviero
Fernanda B M
FB
Camargo
Enilton A
EA
Teixeira
Simone A
SA
Muscará
Marcelo N
MN
De Nucci
Gilberto
G
Zanesco
Angelina
A
Antunes
Edson
E
D000818:Animals; D007172:Erectile Dysfunction / Q000201:enzymology* / Q000209:etiology / Q000628:therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D009569:Nitric Oxide; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases