[Interaction between angiotensin II and endothelin isoforms in the pithed rat]

The 3 isoforms of endothelin (ET) (potent peptidic vasoconstrictor isolated from endothelial cells) induce biphasic pressor effects when given intravenously: a transient hypotension followed by a long-lasting hypertension. The aim of this work was to study the regulatory effect of vascular tone on ET-induced pressor responses in the pithed rat. After pithing, diastolic blood pressure (DBP) was elevated by continuous perfusion of angiotensin-II (AII) or methoxamine (MTX). When DBP was stabilized ET's isoforms (ET-1, ET-2, ET-3) were injected (1 nmol/kg). Solvent injection permitted to assess the stability of AII or MTX perfusions. Intravenous injections of ET induced a sharp hypotension which is more pronounced when initial DBP increased whatever the vasoactive substance used to elevate DBP. The maximal effects of each ET was identical but the hypotension is longer for ET-3 than for ET-1 and ET-2. The following hypertensive phase diminished when DBP increased but is strongly blunted in AII-supported rats when compared to MTX-supported rats. Furthermore, ET-3 appeared to be devoided of hypertensive effect in AII-supported pithed rats. These results indicate that AII is able to modulate ET-induced pressor response, whereas the initial hypotensive phase is only dependent of vascular tone.