THE VASOCONSTRICTION INDUCED BY ENDOTHELIN-1 IS MEDIATED ONLY BY ETA RECEPTORS IN MESENTERIC SMALL RESISTANCE ARTERIES OF SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR-KYOTO RATS

Objective To evaluate the functional responses of mesenteric small res istance arteries of spontaneously hypertensive rats (SHR) and Wistar-K yoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and ab sence of an ETA receptor antagonist drug as well as to an ETB receptor agonist. Methods Twenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed di ameter 100-180 mu m) were dissected and mounted on a micromyograph (Mu lvany's technique). A dose-response curve for response to ET-1 was plo tted for cumulative concentrations (from 10'''(11) to 10(-8) mol/l) in the presence and absence of 10(-6) mol/l FR 139 317 (a selective anta gonist of ETA receptors). In addition, the effects of 10(-7) mol/l N-s uccinyl-[Glu(9), Ala(11,15)]-endothelin 1 fragment 8-21 (IRL 1620, a s elective agonist of ETB receptors) were evaluated. Results The respons e of ET-1 was greater in WKY rats than it was in SHR. Almost all the v asoconstrictor effect of ET-1 could be prevented by addition of FR 139 317, whereas the agonist of ETB receptors had no effect (no change in active force). Conclusions The contractile effects of ET-1 on mesente ric small resistance arteries of SHR and WKY rats are mediated mostly by ETA receptors, whereas ETB receptors play a minor role, if any. It is possible, however, that a vasoconstrictor effect of ETB receptors o n the smooth muscle could be masked by the concomitant stimulation of endothelial ETB vasodilator receptors. (C) Rapid Science Publishers IS SN 0263-6352.