Abstract
Administration of the selective adenosine A1 receptor antagonist, CVT-124, to conscious chronically instrumented rats resulted in significant increases in urine flow rate and sodium excretion without affecting potassium excretion or renal hemodynamics. Its maximum effect was twice that of hydrochlorothiazide which was associated with a significant kaliuresis. The diuretic effect of CVT-124 was less than that observed with furosemide; however, furosemide administration was associated with a large increase in potassium excretion as well as a reduction in glomerular filtration rate. When given at equinatriuretic doses, CVT-124 enhanced the diuretic and natriuretic activity of furosemide without further increasing potassium excretion. In contrast, the combination of hydrochlorothiazide and furosemide resulted in a 3-fold increase in potassium excretion. These data suggest that CVT-124 possesses unique diuretic activity and, as such, it represents a potential new therapeutic in fluid retaining disorders. In addition, its unique mechanism of action suggests that CVT-124 would be effective in otherwise diuretic-resistant patients.
Footnotes
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Send reprint requests to: Dr. Miklos Gellai, SmithKline Beecham, Department of Renal Pharmacology, UW2521, 709 Swedeland Road, Box 1539, King of Prussia, PA 19406-0939.
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↵1 Current address: Sci os, Inc., 800 W. Maude Avenue, Sunnyvale, CA 94086.
- Abbreviations:
- FUR
- furosemide
- HCTZ
- hydrochlorothiazide
- MAP
- mean aortic pressure
- HR
- heart rate
- GFR
- glomerular filtration rate
- RBF
- renal blood flow
- Received January 21, 1998.
- Accepted April 21, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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