Reciprocal changes in EDHF- and NO-system in the female rat mesenteric artery following ovariectomy

To explore the mechanism for vasoprotective action of estrogen in postmenopausal women, we investigated the effect of ovariectomy (OVX) and OVX plus estrogen replacement (ER) on EDHF- and NO-mediated responses in female rat mesenteric arteries. We also examined the changes in the expression of connexin43 (cx43), iNOS, and eNOS together with its regulator proteins such as calmodulin, heat shock protein 90 (hsp90) and caveolin-1 (cav-1). Four weeks following OVX, EDHF-mediated relaxation and membrane hyperpolarization were suppressed, whereas NO-mediated relaxation was enhanced, resulting in no change in total AChinduced relaxation. Expression of cx43 was decreased：expression of eNOS and its positive regulator such as calmodulin and hsp90 was unchanged, whereas that of its negative regulator cav-1 was decreased. Expression of iNOS and plasma NO metabolites were elevated. These changes following OVX were recovered by ER. These results indicate that OVX suppresses EDHF-mediated responses by downregulating gap junctions, whereas it augments NO-mediated responses by downregulating cav-1.