Role of female sex hormones in neuronal nitric oxide release and metabolism in rat mesenteric arteries

Abstract

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.

Different Influences of Extracellular and Intracellular Superoxide on Relaxation Through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries

“…In addition, previous studies have demonstrated that the arterial relaxant response to a cGMP analog is maintained under conditions in which relaxation induced by an intracellular NO donor is impaired by superoxide. 41,42 The finding that the vasorelaxation in response to 8-Br-cGMP remained unchanged by exposure to menadione is in accordance with these studies. Considering our present results as a whole, the downstream signaling pathway of cGMP is probably unaffected by intracellular superoxide.…”

Androgens and Vascular Function

“…The measured NO release seems to come from nerve endings, since preincubation with tetrodotoxin abolished the nitrite release in endothelial-denuded segments from both groups of rats. This result indicates that male sex hormones apparently do not modulate nNOS-derived NO release, in contrast to our observations with female sex hormones in which we found that the loss of these hormones provoked by ovariectomy increased nNOS-derived NO release (Minoves et al, 2002). To study the involvement of neuronal or endothelial NO on vasomotor responses, EFS induced contractile responses in endothelium-denuded mesenteric segments were analyzed by using vascular reactivity technique (Nielsen & Owman, 1971).…”

Hypertension alters the function of nitrergic and sensory innervation in mesenteric arteries from female rats

“…The participation of different innervations may vary between men and women [6][7][8]. Additionally, there are sex differences in hypertension, with the incidence and severity of this condition being lower in women [9].…”