Scheme showing the involvement of the NO-cGMP-PKG and COX-2 pathways in the ACh-induced relaxation when ovarian function is lost.

<p>The encircled +/- symbols indicate the effect of ovariectomy. ACh, after binding to the muscarinic receptor (M-R), induces the release of NO and activates soluble guanylate cyclase (sGC) to produce cGMP, which is reduced by ovariectomy. However, ovariectomy increased the activity of cGMP-dependent protein kinase (PKG) that could account for the maintenance of ACh-induced vasodilation. Ovariectomy also increases the activity of superoxide dismutase (SOD) in an attempt to counterbalance the increased formation of superoxide anion (O₂^.-), leading to increase the participation of hyperpolarization induced by hydrogen peroxide (H₂O₂) and, that in turn, can activate PKG [41]. These mechanisms could counterbalance the predominance of vasoconstrictor prostanoids derived from COX-2 [19] and account for the maintenance of the ACh-induced relaxation in aortas from ovariectomized rats.