Inhibition of renal vasoconstriction induced by intrarenal hypertonic saline by the nonxanthine adenosine antagonist CGS 15943A

JT Callis, CJ Kuan, KR Branch, BC Abels, R Sabra, EK Jackson and RA Branch

Department of Surgery, Vanderbilt University, Nashville, Tennessee.

The hypothesis that intrarenal infusions of hypertonic saline induce endogenous release of adenosine to result in renal vasoconstriction has been investigated in salt-deplete dogs using the nonxanthine adenosine receptor antagonist, CGS 15943A. Intrarenal artery infusions of CGS 15943A induced dose-dependent reductions in the renal vasoconstrictor response to bolus doses of adenosine into the renal artery, without altering base-line blood pressure or renal blood flow. Infusion rates of 10 micrograms/min induced an approximate 50% reduction in response, whereas 100 micrograms/min produced a substantially greater response. There was no inhibition of the renal vasoconstrictor response to angiotensin II and norepinephrine by CGS 15943A at a rate of 100 micrograms/min. Changes in RBF after intrarenal infusion of hypertonic saline were compared between further series of salt-deplete dogs receiving intrarenal artery infusions of either vehicle or CGS 15943A (100 micrograms/min). An initial infusion of hypertonic saline to both groups of dogs induced renal vasodilation followed by vasoconstriction. In dogs subsequently infused with CGS 15943A (100 micrograms/min), the initial renal vasodilation response was similar, but there was an abolition of the later vasoconstrictor response. In contrast, the renal blood flow response to hypertonic saline was unchanged in the vehicle- infused dogs. We conclude that CGS 15943A can selectively block the renal blood flow response to exogenous adenosine without altering baseline renal vascular tone and that the ability of CGS 15943A to abolish the renal vasoconstrictor response to intrarenal hypertonic saline is consistent with the hypothesis that endogenous release of adenosine is involved in mediating the reduction in renal blood flow.

Volume 248, Issue 3, pp. 1123-1129, 03/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics

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