Chronic kinin receptor blockade induces hypertension in deoxycorticosterone‐treated rats

Abstract

1 The contribution of endogenous kinins to the regulation of blood pressure and renal function of Wistar rats was evaluated by use of the new B₂-receptor antagonist, Hoe 140, (d-Arg[Hyp³,Thi⁵,d-Tic⁷,Oic⁸]-bradykinin). 2 Neither Hoe 140 (4 μg h⁻¹ s.c, for 6 weeks), nor vehicle altered systolic blood pressure (SBP, tail-cuff plethysmography) or renal function in rats, under normal conditions. 3 Chronic administration of deoxycorticosterone (DOC, 25 mg kg⁻¹ s.c., weekly) increased SBP slightly only after 6 weeks (from 124 ± 2 to 133 ± 3 mmHg, P < 0.05). An earlier and greater rise in SBP (P < 0.01) occurred when DOC was combined with chronic infusion of Hoe 140 (from 125 ± 1 to 154 ± 3, P < 0.01). The hypertensive effect of Hoe 140 was confirmed by direct measurement of mean blood pressure (143 ± 2 vs 122 ± 2 mmHg in controls, P < 0.01). 4 DOC caused an initial fall, followed by a transitory increase in urinary volume and sodium excretion; thereafter, both parameters returned to baseline. The initial antidiuretic and antinatriuretic effects were enhanced by Hoe 140 (P < 0.05). 5 Urinary prostaglandin E₂ excretion was increased by DOC (from 106 ±3 to 153 ±4 ng 24 h⁻¹, P < 0.01) and this effect was prevented by Hoe 140 (from 95 ± 3 to 104 ± 3 ng 24 h⁻¹, NS). By contrast, the high urinary vasopressin excretion and suppressed plasma renin activity found in DOC-treated rats were not altered by Hoe 140. 6 These data suggest that endogenous kinins play an important role in the regulation of arterial blood pressure under conditions of mineralocorticoid excess.