Effect of Bradykinin-Receptor Blockade on the Response to Angiotensin-Converting–Enzyme Inhibitor in Normotensive and Hypertensive Subjects

作者：James V. Gainer, Jason D. Morrow, Angela Loveland, Debbie J. King, Nancy Jeanne Brown · 发表于：New England Journal of Medicine · 年份：1998 · DOI：10.1056/nejm199810293391804 · 被引用次数：448 · 研究领域：Renin-Angiotensin System Studies、Coagulation, Bradykinin, Polyphosphates, and Angioedema、Protein Hydrolysis and Bioactive Peptides

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 rena...