CHARACTERIZATION OF ENDOTHELIN RECEPTORS IN RAT RENAL-ARTERY IN-VITRO

1 The aim of this study was to investigate the function and characteristics of endothelin receptors in rat main branch renal artery in vitro. 2 Endothelin(ET)-1 (mean EC(50) = 9.8 nM) was approximately 12 fold more potent than ET-3 (mean EG(50) = 120 nM) as a contractile agonist and produced a greater maximum response. In contrast, neither of the ET(B) receptor-selective agonists, alanine([1,3,11,15])ET-1 nor sarafotoxin S6c, (0.1 nM-1 mu M), induced any contractile effect, or any relaxant effect in endothelium-intact preparations pre-contracted with the thromboxane A(2) mimetic, U-46619. Sarafotoxin S6c (30 nM) also failed to induce any further contraction in tissues pre-contracted with an EC(50) concentration of ET-1. 3 The ET(A) receptor-selective antagonist, BQ123, behaved as a weak and variable antagonist of the contractile effects of ET-1 (mean pA(2) estimates in the range 5.8-6.3). In contrast, BQ123 antagonized ET-3 with a potency (mean pA(2) = 7.6) consistent with its affinity for ET(A) receptors. Co-incubation of BQ123 (3 mu M) with the putative ET(B) receptor-selective antagonist, IRL1038 (10 mu M), produced no greater antagonism of ET-1 responses than was induced by BQ123 (3 mu M) alone. 4 In conclusion, ET(B) receptors do not appear to be present in rat main branch renal artery. The contractile effects of ET-3 in this tissue seem to be mediated by ET(A) receptors. While ET(A) receptors partly mediate the contractile effects of ET-1, these data raise the possibility that a population of novel BQ123-insensitive endothelin receptors may also contribute to this response.