Effect of converting enzyme inhibition and angiotensin receptor blockade on the vasoconstriction mediated by alpha 1-and alpha 2-adrenoceptor stimulation in pithed normotensive rats.

Abstract

The effect of functional impairment of the renin-angiotensin system on the vasoconstriction mediated by postsynaptic α1 and α2-adrenoceptors in pithed normotensive rats was studied. Selective α1-adrenoceptor stimulation was induced by intravenously administered cirazoline, whereas B-HT 920 was used as a selective agonists at α2-adrenoceptors. The angiotensin converting enzyme was inhibited by intravenous treatment of the pithed rats with captopril, teprotide or enalapril. Blockade of angiotensin receptors was produced by intravenously applied [Sar1 Ala8]angiotensin II (saralasin). Pretreatment with angiotensin converting enzyme inhibitors or with saralasin in doses which produced a maximal reduction in basal diastolic blood pressure, only slightly attenuated the hypertensive response to cirazoline. In contrast, these drugs provoked a most significant reduction of the α2-adrenoceptor mediated vasoconstriction. Restoration of the basal diastolic blood pressure by intravenous infusion with angiotensin II or with vasopressin completely reversed the inhibitory effect of captopril on the vasopressor response to B-HT 920. One hour after bilateral nephrectomy, captopril still reduced the α2-adrenoceptor mediated vasoconstriction. However, 18–24 h after bilateral nephrectomy, captopril had no additional inhibitory effect on the vasopressor response to selective α2-adrenoceptor stimulation. It is concluded that in pithed normotensive rats the pressor response to α2-adrenoceptor stimulation is significantly potentiated by endogenous angiotensin II, even at low circulating levels of the octapeptide. The modulatory action of angiotensin II on the α-adrenoceptor mediated vasoconstriction probably represents an effect on the basal arteriolar muscular tone rather than a specific interaction.