No abstract

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 [³H]-noradrenaline, that was similar in both young and old SHR rats. Electrical field stimulation induced NO₂^– 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.

This study examines the effects of female sex hormones on the vasoconstrictor response to electrical field stimulation (EFS), as well as the modulation of this response by neuronal NO. For this purpose, segments of denuded superior mesenteric artery from ovariectomized (OvX) female Sprague-Dawley rats and from control rats (in oestrus phase) were used. EFS induced frequency-dependent contractions, which were greater in segments from OvX rats than in those from control rats. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester strengthened EFS-elicited contractions to a greater extent in arteries from OvX rats than in those from control rats. Similar results were observed with the preferential neuronal NO synthase inhibitor 7-nitroindazole. The sensorial neurotoxin capsaicin did not modify EFS-induced contractions in segments from either group. In noradrenaline-precontracted segments, sodium nitroprusside (SNP) induced concentration-dependent relaxation, which was greater in segments from control rats than in those from OvX rats. 8-Bromo-cGMP induced similar concentration-dependent relaxation in noradrenaline-precontracted segments from both OvX and control rats. Diethyldithiocarbamate, a superoxide dismutase (SOD) inhibitor, reduced the relaxation induced by SNP in segments from both groups of rats. SOD, a superoxide anion scavenger, enhanced the relaxation induced by SNP in segments from OvX rats, but did not modify it in segments from control rats. EFS induced NO(-)(2) formation, which was greater in segments from OvX than in those from control rats, and pretreatment with tetrodotoxin, a blocker of nerve impulse propagation, abolished release in both cases. These results suggest that EFS induces greater neuronal NO release in mesenteric segments from OvX rats than in those from control rats and, although NO metabolism is also higher, the contribution of net neuronal NO in the vasomotor response to EFS is greater in segments from OvX rats than in those from control rats.