CARDIOVASCULAR-RESPONSES MEDIATED BY 2 TYPES OF ENDOTHELIN ET(B) RECEPTOR IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

This study shows the effects of a selective endothelin ET(B) receptor agonist, IRL 1720 {Ac-[Ala(11,15)]endothelin-1-(8-21)}, on cardiovascu lar responses in anesthetized spontaneously hypertensive rats and Wist ar-Kyoto rats. Single intravenous bolus injection of IRL 1720 caused a dose-related short-lasting fall in blood pressure, left ventricular p ressure and myocardial contractility. However, repeated intravenous bo lus injection of 10(-5) mol/kg IRL 1720 produced a biphasic response c onsisting of an initial short-lasting decrease followed by a sustained increase in these parameters. The initial decrease was reduced, where as the following increase was enhanced with the repeated injections of IRL 1720. The cardiovascular presser response was not inhibited by th e endothelin ET(A) receptor antagonist, FR139317 1-methyl-1H-indolyl)l propionyl]amino-3-(2-pyridyl) acid). The effects of IRL 1720 were qual itatively similar but more potent in spontaneously hypertensive rats t han in Wistar-Kyoto rats. These results suggest the existence of two t ypes of endothelin ET(B) receptor for IRL 1720: a tachyphylactic endot helin ET(B) receptor that mediates cardiovascular depressor responses and a less tachyphylactic endothelin ET(B) receptor that mediates pres ser responses in the rat.