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

Aims This study examines the effect of ovarian function on thromboxane A(2) (TXA(2)), prostaglandin (PG) I-2, PGF2(alpha), and PGE(2) release as well as the role of these substances in nitric oxide (NO) release and acetylcholine (ACh)-mediated relaxation. Methods and results Aortic 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 TXA(2) synthesis inhibitor furegrelate, the PGI(2) synthesis inhibitor tranytcypromine (TCP), or the thromboxane-prostanoid receptor antagonist SQ-29548. TXA(2), PGI(2), PGF(2 alpha) and PGE(2) release was measured, and the vasomotor effect of exogenous TXA(2), PGI(2), PGF(2 alpha) and PGE(2) 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 TXA(2), PGE(2), and PGE(2). release and the contractile responses induced by exogenous TXA(2), PGF(2 alpha) or PGE(2), while it decreased the PGI(2)-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. Conclusion Despite 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.