QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.117259v1 320/3/1261    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by LeFebvre, J. Articles by Brown, N. J. Search for Related Content PubMed PubMed Citation Articles by LeFebvre, J. Articles by Brown, N. J.

CARDIOVASCULAR

Bradykinin B₂ Receptor Does Not Contribute to Blood Pressure Lowering during AT₁ Receptor Blockade

Division of Clinical Pharmacology, Departments of Medicine and Pharmacology (J.L., J.R.P., L.J.M., N.J.B.) and Department of Biostatistics (A.S., T.G.), Vanderbilt University School of Medicine, Nashville, Tennessee

This study tested the hypothesis that endogenous bradykinin contributes to the effects of angiotensin AT₁ receptor blockade in humans. The effect of the bradykinin B₂ receptor antagonist D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg (HOE-140) (18 µg/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 B₂ receptor.

Address correspondence to: Dr. Nancy J. Brown, 550 Robinson Research Building, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail: nancy.j.brown{at}vanderbilt.edu