Endogenous Bradykinin and the Renin and Pressor Responses to Furosemide in Humans1
- Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee
Abstract
In humans, bradykinin contributes to the acute renin response after ACE inhibition. To further explore the role of endogenous bradykinin in human renin regulation, we determined the effect of HOE 140, a specific bradykinin B2 receptor antagonist, on the renin response to 0.5 mg/kg i.v. furosemide in a randomized, single blind, crossover design study of 10 healthy, salt-replete volunteers. HOE 140 did not affect basal plasma renin activity, aldosterone, mean arterial pressure, or heart rate. Furosemide administration increased plasma renin activity from 1.0 ± 0.2 to 4.5 ± 1.2 ng of angiotensin I/ml/h and there was no effect of HOE 140 (from 1.1 ± 0.2 to 3.9 ± 0.8 ng of angiotensin I/ml/h). Similarly, there was no effect of HOE 140 on the diuretic response to furosemide. Mean arterial pressure increased in response to furosemide after HOE 140 (82 ± 2 to 94 ± 2 mm Hg), but not after vehicle (81 ± 3 to 85 ± 2 mm Hg), whereas heart rate was unchanged. In conclusion, activation of the B2 receptor by endogenous bradykinin does not contribute to the renin response to acute furosemide treatment in humans. However, bradykinin may contribute to blood pressure regulation under conditions in which the renin-angiotensin system is stimulated.
Footnotes
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Send reprint requests to: Nancy J. Brown, M.D., Division of Clinical Pharmacology, Vanderbilt University Medical Center, 560B Medical Research Bldg. 1, Nashville, TN 37232-6602. E-mail:Nancy.Brown{at}mcmail.vanderbilt.edu
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↵1 This study was supported by National Institutes of Health Grants HL56963, GM07569, HL04445, and RR00095 (GCRC). Presented at the 2nd Annual Scientific Meeting of the Association for Patient Oriented Research, Washington, DC, March 11–13, 2000.
- Abbreviations:
- RAS
- renin-angiotensin system
- Ang
- angiotensin
- ACE
- angiotensin-converting enzyme
- PRA
- plasma renin activity
- PGF
- prostaglandin F
- Hct
- hematocrit
- MAP
- mean arterial pressure
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- Received May 25, 2000.
- Accepted July 31, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
