The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A1 adenosine receptor antagonist.
1. The diuretic effect of the selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), was investigated in anaesthetized rats. 2. CPX (0.1 mg kg-1, i.v.) produced significant increases in urine flow, and the excretion rate and fractional excretion of both sodium and chloride. By contrast, CPX administration did not result in any significant change in the excretion of potassium. 3. The diuretic effect of CPX was accompanied by a transient increase in inulin clearance although p-amino-hippurate clearance was unaffected, indicating the CPX induced a temporary elevation of glomerular filtration rate but no change in renal blood flow. 4. The fractional excretion of lithium (a marker of delivery of fluid out of the proximal tubule) was also significantly increased by CPX. However, other measures of tubular function derived from lithium clearance indicated that there were no changes in the handling of sodium or water in the distal regions of the nephron. 5. CPX did not significantly alter the relationship between either free water reabsorption or free water clearance and the distal delivery of sodium, which suggests that CPX does not affect the renal concentration/dilution mechanism. 6. The results of this study show that the diuresis and increased excretion of sodium and chloride induced by CPX (0.1 mg kg-1) in the rat, occurs with only transient elevation in glomerular filtration rate and no change in renal blood flow. The primary reason for the diuresis appears to be inhibition of sodium reabsorption in the proximal tubule. Furthermore, the results provide evidence that production and release of endogenous adenosine modifies renal excretory function via stimulation of the A1 receptor subtype.
Department of Pharmacology, University of Leeds.
R J
RJ
Knight
C J
CJ
Bowmer
M S
MS
Yates
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D002712:Chlorides / Q000097:blood; D004232:Diuretics / Q000494:pharmacology*; D007275:Injections, Intravenous; D007444:Inulin; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D011188:Potassium / Q000097:blood; D058914:Purinergic Antagonists; D051381:Rats; D011910:Rats, Brattleboro; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D002712:Chlorides; D004232:Diuretics; D058914:Purinergic Antagonists; D014970:Xanthines; D007444:Inulin; D008094:Lithium; D012964:Sodium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011188:Potassium; D010130:p-Aminohippuric Acid