Aging increases neuronal nitric oxide release and superoxide anion generation in mesenteric arteries from spontaneously hypertensive rats.
We hypothesized that neuronal NO release as well as its bioavailability and vasomotor response could be affected when aging and hypertension are present simultaneously. The neuronal nitric oxide (NO) release, its metabolism and vasomotor response induced by electrical field stimulation was analyzed in isolated segments of endothelium-denuded mesenteric arteries from young and old spontaneously hypertensive rats (SHR). The nitric oxide synthase (NOS) inhibitor N(G)-nitro-arginine-methyl ester (L-NAME) and NOS inhibitor 7-nitroindazole both strengthened electrical field stimulation-elicited contractions more in arteries from young than aged SHR rats. Superoxide dismutase (SOD) potentiated the L-NAME effect in segments from old rats, whereas catalase decreased the contractions induced by electrical field stimulation and noradrenaline but did not modify the L-NAME effect. In noradrenaline-precontracted segments, sodium nitroprusside induced a similar relaxation in arteries from both experimental groups. This relaxation was increased by SOD in old SHR. 8Br cGMP induced greater relaxation in segments from old than from young SHR. Electrical field stimulation induced a tritium release in arteries preincubated with [(3)H]-noradrenaline, that was similar in both young and old SHR rats. Electrical field stimulation induced NO(2)(-) formation, which was greater in segments from old than young SHR rats. Basal cGMP levels and those stimulated with sodium nitroprusside were similar in segments from both groups. Superoxide anion production was greater from old than young SHR rats. Peroxynitrite production induced by electrical field stimulation was only detected in segments from old SHR. The results obtained in mesenteric arteries from old SHR showed increased neuronal NO release and superoxide anion production with respect to those observed in arteries from young SHR rats. This induced decreased NO bioavailability through peroxynitrite formation. The final effect is to decrease the involvement of neuronal NO in electrical field stimulation-induced vasomotor response in arteries from old SHR rats.
Ferrer
Mercedes
M
Departamentos de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Sánchez
Margarita
M
Minoves
Nuria
N
Salaices
Mercedes
M
Balfagón
Gloria
G
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013481:Superoxides / Q000378:metabolism*; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D009573:Nitrites; D014316:Tritium; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine