Endothelin-3 is a potent pulmonary vasodilator in the rat

The properties of endothelin-3 (ET-3) were investigated in isolated pulmonary artery rings and isolated blood-perfused lungs of the rat. ET-3 elicited a concentration-dependent relaxation of pulmonary artery rings, and effect inhibited by the nitric oxide synthesis inhibitor L-NG-monomethyl-L-arginine. At 0.1 microM, the response to ET-3 was biphasic, resulting in a sustained contraction. In the isolated lung, ET-3 caused a dose-dependent increase in pulmonary arterial pressure. In lungs ventilated with 3% oxygen, 10 nM ET-3 completely reversed the resultant hypoxic vasoconstriction (HPV) by 100 +/- 8%, an effect unchanged by either indomethacin (1 microM) or glibenclamide (10 microM). L-NG-monomethyl-L-arginine attenuated both the ET-3 dilation in prostaglandin F2 alpha-constricted lungs and the dose-dependent vasodilation of HPV by acetylcholine. ET-3 (10 nM) showed the response time to peak pulmonary arterial pressure generation by hypoxia, the size of the response being unchanged. These results demonstrate that ET-3 has both vasodilator and constrictor actions in the rat lung and that, like acetylcholine, the former is mediated in part via the release of nitric oxide. ET-3 also has the ability to modulate HPV.