Androgen deprivation increases neuronal nitric oxide metabolism and its vasodilator effect in rat mesenteric arteries.
This study examines the effects of male sex hormones on the vasoconstrictor response to electrical field stimulation (EFS), as well as neuronal NO modulation of this response. For this purpose, denuded superior mesenteric artery from orchidectomized and control male Sprague-Dawley rats was used. EFS induced similar frequency-dependent contractions in segments from both groups. The NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester strengthened EFS-elicited contractions more in arteries from orchidectomized than from control male rats. The expression of nNOS was more pronounced in segments from control than from orchidectomized animals. Basal and EFS-induced NO release was similar in segments from both groups. In noradrenaline (NA)-precontracted segments, sodium nitroprusside (SNP) induced a concentration-dependent relaxation, that was greater in segments from orchidectomized than control male rats. 8-Bromo-cGMP induced a similar concentration-dependent relaxation in NA-precontracted segments from either group, and the cGMP levels induced by SNP were also similar in the two groups. Superoxide dismutase (SOD), a superoxide anion scavenger, did not modify the relaxation in segments from control male rats. In contrast, SOD enhanced the relaxation induced by SNP in segments from orchidectomized rats, and the effect was reversed by preincubation with SOD plus catalase. The generation of superoxide anion and of peroxynitrite was greater in segments from orchidectomized than control rats. In NA-precontracted segments from control or orchidectomized rats, exogenous peroxynitrite and H(2)O(2) induced a concentration-dependent relaxation. These results suggest that EFS induces a similar nNOS-derived NO release in segments from orchidectomized and control male rats, despite the decrease in nNOS expression in orchidectomized rats. The NO metabolism is higher in segments from orchidectomized male rats due to the increases in anion superoxide generation and peroxynitrite formation. The vasodilator effects of the peroxynitrite and H(2)O(2)0 generated from the NO metabolism are what enhance the functional role of the nNOS-derived NO release in the orchidectomized rats.
Martín
M del Carmen
MC
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Balfagón
Gloria
G
Minoves
Nuria
N
Blanco-Rivero
Javier
J
Ferrer
Mercedes
M
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000502:physiology*; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013481:Superoxides / Q000032:analysis; D014664:Vasodilation
D000726:Androgen Antagonists; D000728:Androgens; D009419:Nerve Tissue Proteins; D013481:Superoxides; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006152:Cyclic GMP; D009638:Norepinephrine