Ethanol relaxes pulmonary artery by release of prostaglandin and nitric oxide

Abstract

Acute-intake of ethanol is associated with vasodilation of vascular smooth muscle (VSM). Relaxation of VSM is dependent, in part, on the actions of nitric oxide (NO) and prostaglandin (PG) produced by endothelial cells (EC) lining the VSM. We examined the effects of endothelium rubbing and inhibition of EC synthesis of NO and PG on ethanol-induced relaxation of bovine pulmonary artery (BPA) and pulmonary vein (BPV) in vitro. Rings of isolated BPA and BPV were mounted in muscle chambers for the isometric recording of force development. Blood vessels were precontracted with an EC 50 concentration of the thromboxane receptor mimetic U46619. Ethanol (0.01, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28% (w/v) produced concentration-dependent relaxation of BPA and BPV. Ethanol-induced relaxation was attenuated in BPA with rubbed EC and by the NO synthase inhibitors, l -N G monomethylarginine (LNMMA, 50 μM) and l-nitroarginine (NOLA, 10 μM), and the prostaglandin cyclooxygenase inhibitor, ibuprofen (10 μM). In contrast, ethanol-induced relaxation of BPV was not affected by endothelium rubbing or by NOLA or LNMMA, but was partially attenuated by ibuprofen. Nitric oxide was measured with the chemiluminescence technique. Ethanol increased the content of NO released under basal conditions by the BPA but did not effect basal NO release from BPV. However, ethanol enhanced bradykinin-induced release of NO from BPA and BPV and, at low concentrations, augmented bradykinin-induced relaxation of both BPA and BPV. These results indicate that arterial smooth muscle relaxation following ethanol administration occurs predominantly by an endothelium-dependent mechanism involving release of both NO and PG, whereas relaxation of venous smooth muscle results from direct stimulation of the smooth muscle. However, ethanol facilitates release of NO and endothelium-dependent relaxation to bradykinin.