ENDOTHELIN RECEPTOR SUBTYPES IN HUMAN VERSUS RABBIT PULMONARY-ARTERIES

We studied which endothelin (ET) receptor subtypes mediate ET-1-induced vasocontraction in the human pulmonary artery (PA) compared with the rabbit PA. ET-1 produced potent contraction in both human and rabbit isolated PAs. In human PA, ET-1-induced contraction was competitively antagonized by BQ-123 (an ET(A) receptor antagonist) with a pA(2) value of 7.68. In rabbit PA, however, even a high concentration of BQ-123 (1 mu M) did not affect the contraction. BQ-3020 (an ET(B) receptor agonist) produced potent contraction in rabbit PA but not in human PA. Binding assays of the membrane preparations showed that human and rabbit PAs contained ET(A) and ET(B) receptors in ratios of 93:7 and 23:77, respectively. These results suggest interspecies differences in the ET receptor subtypes that mediate ET-1-induced vasocontraction; ET(A) receptors are dominant in the human PA, whereas ET(B) receptors are dominant in the rabbit PA. Furthermore, the predominance of ET(A) receptors in human PA was supported by autoradiographical studies. If ET-1 acts as a physiological and/or pathophysiological vasocontractor in the human pulmonary circulation, an ET(A) receptor antagonist would function as a pulmonary vasodilator in humans.