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

Past studies have demonstrated that 17β-estradiol (E₂β) increases endothelial nitric oxide (NO) synthase (eNOS) activity in uterine, heart, and skeletal muscle and in cultured human endothelial cells. However, little is known about E₂β regulation of NO synthesis in the pulmonary vasculature. The present study evaluated E₂β regulation of eNOS function in pulmonary arteries and thoracic aortas. We hypothesized that E₂β upregulates 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 μg/24 h of E₂β or vehicle. Expression of eNOS was evaluated by Western blot 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 E₂β-treated group was enhanced compared with that in control animals. Endothelium-intact aortic rings from E₂β-treated animals also demonstrated augmented endothelium-dependent dilation. Both responses were blocked with NOS inhibition. Immunostaining for eNOS was greater in pulmonary arteries and aortas from E₂β-treated compared with control rats. However, mRNA levels did not differ between groups. Thus we conclude that in vivo E₂β treatment augments endothelium-dependent dilation in aorta and lung, increasing expression of eNOS independently of sustained augmented gene transcription.