title: Endogenous bradykinin and the renin and pressor responses to furosemide in humans.
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 B(2) 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 B(2) 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.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Murphey
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: N J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011188:Potassium / Q000652:urine; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology; D012083:Renin / Q000097:blood* / Q000502:physiology; D016037:Single-Blind Method; D012964:Sodium / Q000652:urine
chemical_list: D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D000450:Aldosterone; D005665:Furosemide; C065679:icatibant; D012964:Sodium; D003404:Creatinine; D012083:Renin; D011188:Potassium; D001920:Bradykinin; D009638:Norepinephrine