Endothelium-dependent hyperpolarization and relaxation are regulated by estrogen through the expression of gap-junctional protein connexin 43 in the rat mesenteric artery

We examined the effect of estrogen on the EDHF-mediated responses and expression of connexin 43 in mesenteric arteries (MAs) from the female rat. Female rats were divided into three groups；sham-operated (control), ovariectomized (OVX) and estrogen replased (ER) groups. Four weeks after the operation, the MAs were excised. Although nitric oxide-induced arterial relaxation and endothelium-independent hyperpolarization by pinacidil were not different among three groups, EDHF-mediated relaxation and hyperpolarization by acetylcholine were markedly reduced in the OVX rat. ER reversed the impaired EDHF responses, hut estrogen per se had no effect when added acutely. The gap junction inhibitor, 18β-glycyrrhetinic acid, inhibited the EDHF-mediated responses in all three groups. Western blot analysis showed that the expression of connexin 43 is reduced in MAs from the OVX rat. Immunohistochemical staining exhibited that connexin 43 is expressed in both arterial endothelium and smooth muscle cells. The stainings of connexin 43 were also reduced in the MAs from the OVX rat. These changes were reversed by ER. These results suggest that gap junctional communication is involved in EDHF responses of the rat MA and that estrogen upregulates EDHF responses through the increased expression of connexin 43 at genomic level.