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


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Abstract

ObjectiveTo evaluate the functional responses of mesenteric small resistance arteries of spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and absence of an ETA receptor antagonist drug as well as to an ETB receptor agonist.MethodsTwenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed diameter 100–180 μm) were dissected and mounted on a micromyograph (Mulvany's technique). A dose-response curve for response to ET-1 was plotted 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 antagonist of ETA receptors). In addition, the effects of 10−7 mol/l N-succinyl-[Glu9, Ala11,15]-endothelin 1 fragment 8–21 (IRL 1620, a selective agonist of ETB receptors) were evaluated.ResultsThe response of ET-1 was greater in WKY rats than it was in SHR. Almost all the vasoconstrictor 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).ConclusionsThe contractile effects of ET-1 on mesenteric 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 on the smooth muscle could be masked by the concomitant stimulation of endothelial ETB vasodilator receptors.

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