Endothelin 1 causes pulmonary vasodilation in rats

Publisher Website
Google Scholar
Abstract
Endothelin 1 (ET-1), a peptide produced by endothelial cells, causes transient dilation of some systemic vascular beds. To test whether low concentrations of ET-1 could also dilate the pulmonary vascular bed, we examined its effects in isolated blood- and salt solution-perfused rat lungs and in conscious catheterized rats. In blood-perfused lungs undergoing hypoxic (3% O2) vasoconstriction, repeated additions of 0.5 nM ET-1 to the perfusate elicited transient partial vasodilations. The higher concentration of 5 nM caused a larger transient vasodilation followed by vasoconstriction. In nine conscious rats exposed to 8% O2, intravenous ET-1 (0.2 nmol/kg) reversed the hypoxic pressor response by 63 .+-. 8% without affecting cardiac output. In eight salt solution-perfused lungs vasoconstricted with 25 mM KCl, 0.5 nM ET-1 caused a maximum vasodilation of 35 .+-. 3% with a half-life of 10.7 .+-. 1.1 min. The vasodilation was not inhibited by blockers of cyclooxygenase (3.1 .mu.M meclofenamate), platelet-activating factor receptors (10 .mu.M Web 2086), histamine H1 receptors (50 .mu.M chlorpheniramine), or endothelium-derived relaxing factor activity (10 .mu.M hemoglobin and 50 .mu.M methylene blue). However, it was reduced by .apprx.50% with the K+ channel blockers, tetraethylammonium chloride (10 mM) and glybenclamide (10 .mu.M), and the inhibitor of Na+-K+ pumping, ouabain (0.1 mM). These results indicate that ET-1 is a potent dilator of the pulmonary vascular bed of the rat and that the mechanism of dilation may involve activation of ATP-sensitive K+ channels and membrane hyperpolarization.