Blunting of the renal response to volume expansion by a bradykinin receptor antagonist: Influence of denervation

M. L. Kauker, P. L. Zhang, D. W. Zeigler, K. P. Patel

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Abstract

The interaction of renal sympathetic nervous influences with the intrarenal kallikrein-kinin system was examined during graded expansion of the extracellular fluid volume in rats. One group of rats was pretreated with a specific and highly efficacious competitive antagonist of bradykinin receptor (BKRA), whereas the other group received only a vehicle infusion. The left kidney was denervated in each animal and the right kidney remained intact. After control observations, the extracellular fluid volume was expanded by a continuous i.v. infusion of 0.9% NaCl at a rate of 0.25% of body weight per minute for 40 min (VE). During VE urine flow and sodium excretion increased significantly from both kidneys in each of the two treatment groups. The diuretic response was greatest in the denervated kidneys of vehicle-pretreated rats, where urine flow increased by 70 ± 13 μl·min-1.g kwt-1. This exaggerated diuresis was blunted by pretreatment with the BKRA. In the denervated and BKRA-treated kidneys, the VE-induced mean urine flow increase was limited to 31 ± 5 μl·min-1.g kwt-1 (P < .05 compared with vehicle-pretreated, denervated kidneys). The change in net sodium excretion produced by VE was also reduced by BKRA pretreatment in the denervated kidneys from 13.2 ± 2.6 to 5.5 ± 1.3 μEq.min-1.g kwt-1 (P < .05, vehicle vs. BKRA). In the intact kidneys the diuretic and natriuretic responses to VE were similar in the vehicle- and BKRA-pretreated rats. Glomerular filtration rate and filtration fraction were increased significantly and to the same extent by VE under all experimental conditions. Effective renal plasma flow and mean blood pressure were not altered by VE. The observed blunting of the diuretic and natriuretic responses to VE by a BKRA in the denervated kidneys is consistent with the contribution of kinins to the renal response to VE by inhibiting the tubular reabsorption of salt and water. This effect of kinins may be obscured by renal sympathetic influences in the intact kidney but uncovered by denervation of the kidney.

Original languageEnglish (US)
Pages (from-to)866-870
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume258
Issue number3
StatePublished - Nov 26 1991

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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