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

Gonzales, Rayna J., Benjimen R. Walker, and Nancy L. Kanagy. 17b-Estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta. Am J Physiol Lung Cell Mol Physiol 280: L555–L564, 2001.—Past studies have demonstrated that 17b-estradiol (E2b) 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 E2b regulation of NO synthesis in the pulmonary vasculature. The present study evaluated E2b regulation of eNOS function in pulmonary arteries and thoracic aortas. We hypothesized that E2b 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 mg/24 h of E2b 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 E2b-treated group was enhanced compared with that in control animals. Endothelium-intact aortic rings from E2b-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 E2b-treated compared with control rats. However, mRNA levels did not differ between groups. Thus we conclude that in vivo E2b treatment augments endothelium-dependent dilation in aorta and lung, increasing expression of eNOS independently of sustained augmented gene transcription.