Ovariectomy increases the formation of prostanoids and modulates their role in acetylcholine-induced relaxation and nitric oxide release in the rat aorta

Abstract

Aims This study examines the effect of ovarian function on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF2α, and PGE2 release as well as the role of these substances in nitric oxide (NO) release and acetylcholine (ACh)-mediated relaxation.Methods and resultsAortic segments from ovariectomized and control female Sprague-Dawley rats were used. Cyclooxygenase (COX-1 and COX-2) expression was studied. ACh-induced relaxation was analysed in the absence and presence of the COX-2 inhibitor NS-398, the TXA2 synthesis inhibitor furegrelate, the PGI2 synthesis inhibitor tranylcypromine (TCP), or the thromboxane-prostanoid receptor antagonist SQ-29548. TXA2, PGI2, PGF2α, and PGE2 release was measured, and the vasomotor effect of exogenous TXA2, PGI2, PGF2α, and PGE2 was assessed. Basal and ACh-induced NO release in the absence and presence of NS-398, furegrelate, TCP, or TCP plus furegrelate was studied. Ovariectomy did not alter or increased COX-1 or COX-2 expression, respectively. NS-398 decreased, and furegrelate did not change, the ACh-induced relaxation in arteries from both groups. SQ29,548 decreased the ACh-induced relaxation only in aortas from ovariectomized rats. TCP decreased the ACh-induced relaxation in both groups, and furegrelate or SQ29,548 totally restored that response only in aortas from control rats. Ovariectomy increased the ACh-induced TXA2, PGI2, and PGE2 release and the contractile responses induced by exogenous TXA2, PGF2α, or PGE2, while it decreased the PGI2-induced vasodilator response. In aortas from control rats, NS-398 did not alter the ACh-induced NO release, and furegrelate, TCP, or TCP plus furegrelate increased that release. In arteries from ovariectomized rats, NS-398, furegrelate, TCP, or TCP plus furegrelate decreased the ACh-induced NO release.ConclusionDespite the prevalence of vasoconstrictor prostanoids derived from COX-2 in aortas from ovariectomized rats, the ACh-induced relaxation is maintained, probably as consequence of the positive regulation that prostanoids exert on eNOS activity.