Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects.

Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ
N Engl J Med. 1998 339 (18): 1285-92

PMID: 9791144 · DOI:10.1056/NEJM199810293391804

BACKGROUND - Angiotensin-converting-enzyme (ACE) inhibitors not only decrease the production of angiotensin II but also decrease the degradation of bradykinin. In this study, a specific bradykinin-receptor antagonist, icatibant acetate (HOE 140), was used to determine the contribution of bradykinin to the short-term effects of ACE inhibition on blood pressure and plasma renin activity in both normotensive and hypertensive subjects.

METHODS - We compared the hemodynamic, renal, and endocrine effects of captopril alone (25 mg), captopril plus icatibant (100 microg per kilogram of body weight), the angiotensin II subtype 1-receptor antagonist losartan (75 mg), and placebo in 20 subjects with normal blood pressure and 7 subjects with hypertension. The subjects were studied while they were salt depleted (i.e., in balance on a diet in which they were allowed 10 mmol of sodium per day). The drugs were administered on four separate study days in a single-blind, randomized fashion.

RESULTS - The coadministration of icatibant significantly attenuated the hypotensive effect of captopril (maximal decrease in mean arterial pressure for all subjects combined, 10.5+/-1.0 mm Hg, as compared with 14.0+/-1.0 mm Hg for captopril alone; P=0.001), in such a way that the decrease in blood pressure after the administration of captopril plus icatibant was similar to that after the administration of losartan (maximal decrease in mean arterial pressure, 11.0+/-1.7 mm Hg). Icatibant did not alter the renal hemodynamic response to captopril, but it significantly altered the change in plasma renin activity in response to ACE inhibition (-0.4+/-0.4 ng of angiotensin I per milliliter per hour, as compared with 2.0+/-0.7 ng per milliliter per hour for captopril alone; P=0.007). The magnitude of these effects was similar in both the normotensive and the hypertensive subjects, as well as in both the black subjects and the white subjects.

CONCLUSIONS - These data confirm that bradykinin contributes to the short-term effects of ACE inhibition on blood pressure in normotensive and hypertensive persons and suggest that bradykinin also contributes to the short-term effects of ACE inhibition on the renin-angiotensin system.

MeSH Terms (19)

Adrenergic beta-Antagonists Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents Blood Pressure Bradykinin Bradykinin Receptor Antagonists Captopril Diet, Sodium-Restricted Drug Interactions Drug Therapy, Combination Female Humans Hypertension Kidney Losartan Male Reference Values Renin-Angiotensin System Single-Blind Method

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