Characterization of endothelin receptors in rat renal artery in vitro

Abstract

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)-l (mean ECjO = 9.8 nM) was approximately 12 fold more potent than ET-3 (mean EC50 = 120 nM) as a contractile agonist and produced a greater maximum response. In contrast, neither of the ETB receptor-selective agonists, alanine1l'3"1 "'ET-1 nor sarafotoxin S6c, (0.1 nM-I1tM), induced any contractile effect, or any relaxant effect in endothelium-intact preparations pre-contracted with the thromboxane A2 mimetic, U-46619. Sarafotoxin S6c (30 nM) also failed to induce any further contraction in tissues pre-contracted with an ECm concentration of ET-1.3 The ETA receptor-selective antagonist, BQ123, behaved as a weak and variable antagonist of the contractile effects of ET-1 (mean pA2 estimates in the range 5.8-6.3). In contrast, BQ123 antagonized ET-3 with a potency (mean pA2= 7.6) consistent with its affinity for ETA receptors. Co-incubation of BQ123 (3 IM) with the putative ETB receptor-selective antagonist, IRL1038 (10lM), produced no greater antagonism of ET-1 responses than was induced by BQ123 (3 JsM) alone. 4 In conclusion, ETB 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 ETA receptors. While ETA 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.

Endothelin System–Dependent Cardiac Remodeling in Renovascular Hypertension

“…This finding is in agreement with a recent report 21 also showing no effect of a combined ETA/ETB receptor antagonist on blood pressure in rats with renovascular hypertension. The present study additionally demonstrated that the long-term selective blockade of the ETA receptor with BQ 123 5 and of the ETB receptor with the selective ETB antagonist IRL 1038 27,28 did not lower blood pressure in 2K1C rats, indicating that the endothelin system does not contribute to the maintenance of high blood pressure in renovascular hypertension.…”

Functional characterization and expression of endothelin receptors in rat carotid artery: involvement of nitric oxide, a vasodilator prostanoid and the opening of K+ channels in ETB‐induced relaxation

“…The interaction between the ET‐1 antagonist and its receptors is reversible and BQ123 acts as a competitive antagonist ( Ihara et al ., 1992 ). Finally, BQ123 was left in contact with the carotids for 30 min, which is a period of incubation sufficient to achieve the equilibrium conditions ( Ihara et al ., 1992 ; Clark & Pierre, 1995 ). Thus, four of the five possibilities raised were excluded.…”

Comparison of the contractile effects and binding kinetics of endothelin‐1 and sarafotoxin S6b in rat isolated renal artery

“…Furthermore, in the current study, agonist dependency of antagonist potency was not limited to BQ‐123, but was also observed with another ET A receptor antagonist, FR‐139317. It is therefore unlikely that the seemingly contradictory results of Clark & Pierre (1995) and Seo & Lüscher (1995) can be attributed to differences in the selectivity of the antagonists or in the strain of rat studied.…”

“…Recently, Clark & Pierre (1995) showed that ET‐1‐induced contractions of renal arteries from Sprague‐Dawley rats were not mediated by ET B receptors, yet were only poorly inhibited by an ET A receptor‐selective antagonist BQ‐123. In contrast, BQ‐123 antagonized ET‐3 with a potency consistent with its affinity for typical ET A receptors.…”