17beta-estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta.
Past studies have demonstrated that 17beta-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, little is known about E(2)beta regulation of NO synthesis in the pulmonary vasculature. The present study evaluated E(2)beta regulation of eNOS function in pulmonary arteries and thoracic aortas. We hypothesized that E(2)beta 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 microg/24 h of E(2)beta 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 E(2)beta-treated group was enhanced compared with that in control animals. Endothelium-intact aortic rings from E(2)beta-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 E(2)beta-treated compared with control rats. However, mRNA levels did not differ between groups. Thus we conclude that in vivo E(2)beta treatment augments endothelium-dependent dilation in aorta and lung, increasing expression of eNOS independently of sustained augmented gene transcription.
Gonzales
R J
RJ
Vascular Physiology Group, Department of Cell Biology and Physiology, Health Sciences Center, University of New Mexico, Albuquerque, New Mexico 87131-5218, USA. rgonzales@salud.unm.edu
Walker
B R
BR
Kanagy
N L
NL
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D010052:Ovariectomy; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D019335:Nitroarginine; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat