17 beta-Estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta

Past studies have demonstrated that 17 beta -estradiol (E(2)beta) increases endothelial nitric oxide (NO) synthase (eNOS) activity in uterine, heart, and skeletal muscle and in cultured human endothelial cells. However, littl e is known about E(2)beta regulation of NO synthesis in the pulmonary vascu lature. The present study evaluated E(2)beta regulation of eNOS function in pulmonary arteries and thoracic aortas. We hypothesized that E(2)beta upre gulates vascular NO release by increasing eNOS expression. To test this, NO -dependent vasodilation was assessed in isolated perfused lungs and aortic rings from ovariectomized Sprague-Dawley rats treated for 1 wk with 20 mug/ 24 h of E(2)beta or vehicle. Expression of eNOS was evaluated by Western bl ot and immunohistochemistry. Also, a RNase protection assay determined eNOS mRNA levels in lung and aortic homogenates from control and treated rats. Vasodilation to ionomycin in lungs from the E(2)beta -treated group was enh anced compared with that in control animals. Endothelium-intact aortic ring s from E(2)beta -treated animals also demonstrated augmented endothelium-de pendent dilation. Both responses were blocked with NOS inhibition. Immunost aining for eNOS was greater in pulmonary arteries and aortas from E(2)beta -treated compared with control rats. However, mRNA levels did not differ be tween groups. Thus we conclude that in vivo E(2)beta treatment augments end othelium-dependent dilation in aorta and lung, increasing expression of eNO S independently of sustained augmented gene transcription.