Chronic inhibition of bradykinin B2-receptors enhances the slow vasopressor response to angiotensin II.
The contribution of endogenous kinins in the regulation of blood pressure of angiotensin-treated rats was evaluated using the new bradykinin B2-receptor antagonist Hoe 140 (D-Arg,[Hyp3,Thi5,D-Tic7, Oic8]-bradykinin). Chronic infusion of Hoe 140 at 75 nmol/d (a dose able to inhibit the vasodepressor effect of an intra-aortic bolus injection of 0.85 nmol/kg bradykinin) did not alter systolic blood pressure (tail-cuff plethysmography). Chronic infusion of angiotensin II (Ang II) induced a dose-related increase in systolic blood pressure and plasma Ang II levels. The vasopressor effect of 40 or 100 nmol/d Ang II was enhanced in rats given chronic infusion of Hoe 140 (by 12 and 14 mm Hg, respectively), whereas the increase in plasma Ang II levels remained unaltered. Furthermore, a low nonpressor dose of Ang II (20 nmol/d) was then able to increase blood pressure during chronic blockade of bradykinin receptors by Hoe 140 (from 126 +/- 3 to 137 +/- 3 mm Hg, P < .05). Combined infusion of 20 nmol Ang II and Hoe 140 did not alter the urinary excretion of sodium and water despite the fact that blood pressure was increased. Potentiation of the pressure effect of Ang II by Hoe 140 was confirmed by direct measurement of mean blood pressure (125 +/- 2 versus 108 +/- 2 mm Hg at 20 nmol, 123 +/- 2 versus 110 +/- 2 mm Hg at 40 nmol, and 139 +/- 2 versus 125 +/- 3 mm Hg at 100 nmol Ang II, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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