THE DIURETIC ACTION OF 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE, A SELECTIVE A(1)-ADENOSINE RECEPTOR ANTAGONIST

1 The diuretic effect of the selective A1 adenosine receptor antagonis t, 8-cyclopentyl-1,3-dipropylxanthine (CPX), was investigated in anaes thetized rats. 2 CPX (0.1 mg kg-1, i.v.) produced significant increase s in urine flow, and the excretion rate and fractional excretion of bo th sodium and chloride. By contrast, CPX administration did not result in any significant change in the excretion of potassium. 3 The diuret ic effect of CPX was accompanied by a transient increase in inulin cle arance although p-amino-hippurate clearance was unaffected, indicating the CPX induced a temporary elevation of glomerular filtration rate b ut no change in renal blood flow. 4 The fractional excretion of lithiu m (a marker of delivery of fluid out of the proximal tubule) was also significantly increased by CPX. However, other measures of tubular fun ction derived from lithium clearance indicated that there were no chan ges in the handling of sodium or water in the distal regions of the ne phron. 5 CPX did not significantly alter the relationship between eith er free water reabsorption or free water clearance and the distal deli very of sodium, which suggests that CPX does not affect the renal conc entration/dilution mechanism. 6 The results of this study show that th e diuresis and increased excretion of sodium and chloride induced by C PX (0.1 mg kg-1) in the rat, occurs with only transient elevation in g lomerular filtration rate and no change in renal blood flow. The prima ry reason for the diuresis appears to be inhibition of sodium reabsorp tion in the proximal tubule. Furthermore, the results provide evidence that production and release of endogenous adenosine modifies renal ex cretory function via stimulation of the A1 receptor subtype.