Aging Increases Neuronal Nitric Oxide Release and Superoxide Anion Generation in Mesenteric Arteries from Spontaneously Hypertensive Rats

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.

l-carnitine and its propionate: Improvement of endothelial function in SHR through superoxide dismutase-dependent mechanisms

“…The increased vascular generation of superoxide (O z2 2 ) anions observed in these studies [3] rapidly inactivates endothelial NO and thereby alters vascular tone [4]. Recently, it has been shown that either the enhanced expression of the O z2 2 generating enzyme, NAD(P)H oxidase subunits nox1, nox2, nox4 and p22phox [5] or the increased activity of this system [4] are involved in the generation of vascular oxidative stress.…”

Chronic HgCl2 treatment increases vasoconstriction induced by electrical field stimulation: role of adrenergic and nitrergic innervation

“…EFS produced a vasoconstrictor response, which is the integrated result of release of neurotransmitters, mainly NA, NO and CGRP [31,[44][45][46]. In addition, the role of adrenergic, nitrergic and sensory innervations may change depending on the pathophysiological conditions [30,47,48].…”

Differential Modulation of Nitric Oxide Synthases in Aging: Therapeutic Opportunities

“…However, this negative modulatory effect by nNOS is significantly impaired in old rats (Ferrer and Balfagon, 2001). Furthermore, old hypertensive rats exhibit just a minor increase of vasoconstriction after pre-incubation with a selective nNOS inhibitor (Ferrer et al, 2003). These findings suggest that nNOS-derived NO in perivascular nitrergic innervation modulates microvascular tone by reducing α-adrenergic vasoconstriction and that its absence may account for the abnormal vasoconstrictor tone in aged arterioles (Ferrer and Balfagon, 2001; Ferrer et al, 2003).…”