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

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 (B...

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Published in:The Journal of pharmacology and experimental therapeutics Vol. 258; no. 3; p. 866
Main Authors: Kauker, M L, Zhang, P L, Zeigler, D W, Patel, K P
Format: Journal Article
Language:English
Published: United States 01.09.1991
Subjects:
Animals
Blood Pressure - physiology
Denervation
Extracellular Space - physiology
Kidney - innervation
Kidney - metabolism
Kidney - physiology
Male
Rats
Rats, Inbred Strains
Receptors, Bradykinin
Receptors, Neurotransmitter - antagonists & inhibitors
Sodium - urine
Sympathetic Nervous System - physiology
Urodynamics
ISSN:0022-3565
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Summary: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 microliters.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 microliters.min(-1).g kwt(-1) (P less than .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 microEq.min-1.g kwt(-1) (P less than .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.
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ISSN:0022-3565
DOI:10.1016/S0022-3565(25)20284-1