ENDOTHELIN(B) RECEPTORS IN RABBIT PULMONARY RESISTANCE ARTERIES - EFFECT OF LEFT-VENTRICULAR DYSFUNCTION

The endothelin (ET) receptor that mediates vasoconstriction of the iso lated rabbit pulmonary resistance artery was characterized using selec tive ET receptor agonists and antagonists. We also examined changes in ET-induced vasoconstriction brought about by left ventricular dysfunc tion using the rabbit coronary ligation model. The rank order of poten cy for contraction was sarafotoxin S6c (S6c) > ET-1 = ET-3, which is c haracteristic of an ETB-like receptor. The combined ETA/ETB receptor a ntagonist SB209670 (1 mu M) antagonized responses to ET-1 and S6c with estimated pK(b) values of 6.8 +/- 0.2 and 7.8 +/- 0.2, respectively. BQ788 (1 mu M) antagonized responses to S6c and ET-3 (but not ET-1) wi th estimated pK(b) values of 7.1 +/- 0.2 and 6.6 +/- 0.1, respectively . The ETA receptor antagonist FR139317 (1 mu M), either alone or in co mbination with BQ788, did not inhibit responses to ET-1. The profile o f the ET-1 response was not altered by left ventricular dysfunction. I n control rabbits, the inhibitor of nitric oxide synthase N-omega-nitr o-L-arginine methyl ester (100 mu M) had no significant effect on the potency of either ET-1 or S6c. In the coronary-ligated rabbits, howeve r, it significantly increased the potency (10-15-fold) of both ET-1 an d S6c. These results suggest that the ET receptor that mediates contra ction in rabbit pulmonary resistance arteries has the characteristics of an ETB-like receptor. The responses to ET-1 are not altered by LVD but may be modified by increased release of nitric oxide.