Influence of the adenosine receptor antagonist, CGS 15943A, on renal function after reconstruction of chronic renal artery stenosis in the dog.
Surgical reconstruction of chronic renal artery stenosis may correct the anatomical defect but not result in an initial improvement in function of the revascularized kidney. The functional and hemodynamic changes associated with surgical correction of the one-clip, two-kidney, canine model of renovascular hypertension were studied. In 14 dogs, a surgical clip was placed across the proximal renal artery and tightened to decrease perfusion pressure (RPP) and blood flow (RBF). One month later, measurements were obtained distal to the constriction, before and 30 min after vascular reconstruction. Surgical reconstruction was associated with a rise in RPP (86%, P less than .001), renal vascular resistance (47%, P less than .001) and RBF (22%, P less than .05). Creatinine clearance (CCr) remained unchanged, but a significant negative association existed between initial CCr and change in CCr. The role of adenosine in mediating these changes was examined using the selective receptor antagonist, CGS 15943A (CGS), or its vehicle. After vascular reconstruction, vehicle dogs sustained a marked increase in renal vascular resistance, with a 60 +/- 8 mm Hg rise in RPP, but only an 18% rise in RBF. In contrast, renal vascular resistance was unchanged in the CGS group, with a 56 +/- 7 mm Hg increase in RPP and a 69% increase in RBF (P less than .0001). CCr was not changed by either vascular reconstruction or CGS 15943A. Vascular reconstruction was associated with increases in urinary flow rate and sodium excretion in both groups, but this change was significantly greater in the CGS group.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Surgery, Vanderbilt University, Nashville, Tennessee.
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D000241:Adenosine / Q000037:antagonists & inhibitors*; D000818:Animals; D003251:Constriction, Pathologic; D003404:Creatinine / Q000378:metabolism; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D058914:Purinergic Antagonists; D011799:Quinazolines / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects* / Q000601:surgery; D012079:Renal Circulation / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*
D058914:Purinergic Antagonists; D011799:Quinazolines; D014230:Triazoles; D003404:Creatinine; D000241:Adenosine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine