PT - JOURNAL ARTICLE AU - Docherty, Cheryl C. AU - Maclean, Margaret R. TI - Endothelin<sub>B</sub> Receptors in Rabbit Pulmonary Resistance Arteries: Effect of Left Ventricular Dysfunction DP - 1998 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 895--903 VI - 284 IP - 3 4099 - http://jpet.aspetjournals.org/content/284/3/895.short 4100 - http://jpet.aspetjournals.org/content/284/3/895.full SO - J Pharmacol Exp Ther1998 Mar 01; 284 AB - The endothelin (ET) receptor that mediates vasoconstriction of the isolated rabbit pulmonary resistance artery was characterized using selective ET receptor agonists and antagonists. We also examined changes in ET-induced vasoconstriction brought about by left ventricular dysfunction using the rabbit coronary ligation model. The rank order of potency for contraction was sarafotoxin S6c (S6c) &gt; ET-1 = ET-3, which is characteristic of an ETB-like receptor. The combined ETA/ETB receptor antagonist SB209670 (1 μM) antagonized responses to ET-1 and S6c with estimated pKb values of 6.8 ± 0.2 and 7.8 ± 0.2, respectively. BQ788 (1 μM) antagonized responses to S6c and ET-3 (but not ET-1) with estimated pKb values of 7.1 ± 0.2 and 6.6 ± 0.1, respectively. The ETA receptor antagonist FR139317 (1 μM), either alone or in combination with BQ788, did not inhibit responses to ET-1. The profile of the ET-1 response was not altered by left ventricular dysfunction. In control rabbits, the inhibitor of nitric oxide synthaseNω-nitro-L-arginine methyl ester (100 μM) had no significant effect on the potency of either ET-1 or S6c. In the coronary-ligated rabbits, however, it significantly increased the potency (10–15-fold) of both ET-1 and S6c. These results suggest that the ET receptor that mediates contraction 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. The American Society for Pharmacology and Experimental Therapeutics