Mechanisms by which endothelin-1 induces pulmonary vasoconstriction in the rabbit

Mechanisms by which endothelin 1 induces pulmonary vasocon-striction in the rabbit. J. Appl. Physiol. 71(2): 410-416, 1991.-To investigate the mechanisms by which endothelin 1 (ET-l) causes pulmonary vasoconstriction, we studied the effect of syn-thetic ET-l on pulmonary vascular tone in the buffer-perfused isolated rabbit lung. In nanomolar concentrations (1.2-8 nM), ET-l causes a dose-dependent increase in pulmonary arterial pressure that persists for 21 h (increase in pressure 19 * 2 mmHg with ET-l vs. 2 t 1 with vehicle, P < 0.0001). Reduction of calcium availability with verapamil, cadmium, or a calcium-free buffer significantly blunts the increase in pressure caused by ET-l. Pretreatment with a calcium-free buffer plus the chelator ethylene glycol-bis(P-aminoethyl ether)-N&N’, Wtetraacetic acid (EGTA) completely eliminates the vasocon-striction. Three different inhibitors of protein kinase C, phlore