title: Evidence that intrarenal bradykinin plays a role in regulation of renal function.
abstract: Bradykinin (BK) is produced by the kidney, but the role of the renal kallikrein-kinin system (KKS) in the control of renal function is not understood. We studied the effects of intrarenal infusion of the BK antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid (BKA, n = 5) and BK (n = 4) alone or combined with antagonist (BKA 0.025 ng.kg-1 x min-1 + BK 0.25 ng.kg-1 x min-1, n = 4) in uninephrectomized conscious dogs in sodium balance at 10 and 80 meq/day. During low sodium intake, administration of BKA (infusions from 0.025 to 2.5 ng.kg-1 x min-1) caused a significant antidiuresis (P < 0.0001) and antinatriuresis (P < 0.0001) and a decrease in fractional sodium excretion (P < 0.0001). There were no changes in estimated renal plasma flow (RPF) or glomerular filtration rate during intrarenal administration of BKA at 0.025 and 0.25 ng.kg-1 x min-1. A dose of 2.5 ng.kg-1 x min-1 BKA caused a significant decrease in RPF. There were no changes in plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure during intrarenal BKA administration. At 80 meq/day sodium balance (n = 5), intrarenal administration of BKA did not cause any systemic or renal effects. Intrarenal administration of BK at 0.25 ng.kg-1 x min-1 during low sodium balance caused an increase in urine flow rate and urinary sodium excretion. Coinfusion of BK with BKA completely abrogated the renal excretory changes induced by BKA. These data suggest that intrarenal KKS plays a role in control of renal function largely by a tubular mechanism during low sodium intake.
authors.affiliation: Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: H M
authors.initials: HM
authors.lastname: Siragy
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004039:Diet, Sodium-Restricted; D004285:Dogs; D005463:Fluoroacetates; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
chemical_list: D005463:Fluoroacetates; D009842:Oligopeptides; C069620:B 3824; D012964:Sodium; D001920:Bradykinin