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J Pharmacol Exp Ther. 2007 Mar;320(3):1261-7. Epub 2006 Dec 20.

Bradykinin B(2) receptor does not contribute to blood pressure lowering during AT(1) receptor blockade.

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  • 1Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA.


This study tested the hypothesis that endogenous bradykinin contributes to the effects of angiotensin AT(1) receptor blockade in humans. The effect of the bradykinin B(2) receptor antagonist d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Tic-Oic-Arg (HOE-140) (18 microg/kg/h i.v. for 6 h) on hemodynamic and endocrine responses to acute and chronic (1-month) treatment with valsartan (160 mg/day) was determined in 13 normotensive and 12 hypertensive salt-deplete subjects. Acute valsartan increased plasma renin activity (PRA) from 5.3 +/- 9.9 to 15.6 +/- 19.8 ng of angiotensin (Ang) I/ml/h (P < 0.001) and decreased aldosterone from 18.3 +/- 10.5 to 12.0 +/- 9.6 ng/dl (P < 0.001). Chronic valsartan significantly increased baseline PRA (10.5 +/- 15.5 ng of Ang I/ml/h; P = 0.004) but did not affect baseline angiotensin-converting enzyme activity or aldosterone. HOE-140 tended to increase the PRA response to valsartan, and it attenuated the decrease in aldosterone following chronic valsartan (P = 0.03). Acute valsartan decreased mean arterial pressure 12.7 +/- 6.9% (from 100.2 +/- 8.4 to 87.5 +/- 9.8 mm Hg in hypertensives and from 82.4 +/- 8.6 to 70.3 +/- 8.4 mm Hg in normotensives). HOE-140 did not affect the blood pressure response to either acute (effect of valsartan, P < 0.001; effect of HOE-140, P = 0.98) or chronic (valsartan, P = 0.01; HOE-140, P = 0.84) valsartan. Plasma cGMP was increased significantly during chronic valsartan (P = 0.048) through a bradykinin receptor-independent mechanism (effect of HOE-140, P = 0.13). Both acute (P < 0.001) and chronic (P < 0.001) valsartan increased heart rate. HOE-140 augmented the heart rate response to chronic valsartan (P = 0.04). These data suggest that endogenous bradykinin does not contribute significantly to the blood pressure-lowering effect of valsartan through its B(2) receptor.

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