Use of renal artery infusion in dogs for evaluation of diuretics.
In this paper we report on a series of experiments evaluating a model of renal artery infusion (RAI) as a screening technique for comparison of new diuretics, and test some assumptions underlying its use. The femoral artery and vein of Beagle dogs were catheterized for the infusion of solutions, measurement of arterial blood pressure and the sampling of arterial blood. The left kidney was isolated through a flank incision, and a 27 ga. needle, connected to PE10 tubing, was inserted into the renal artery for administration of test diuretics. Both ureters were catheterized for collection of urine. Effects on renal function were assessed during control, drug infusion, and recovery periods. At low doses, the loop diuretics, furosemide (FUR) and MK447, increased urinary excretion within the first 15 min of infusion. The effect of muzolimine, another loop diuretic, was delayed until about 45 min after initiation of infusion. Renal function returned to baseline after cessation of drug infusion. At high doses, excretion was increased by all the loop diuretics within the first 15 min of infusion. The response to muzolimine and MK447 was prolonged well into the recovery period, while that to furosemide returned promptly to baseline. Two distal diuretics, hydrochlorothiazide and amiloride, caused a significant increase in urinary excretion at both low and high doses. The magnitude of the response was significantly less than for the loop diuretics. Low doses of the loop diuretics had very little effect on the contralateral kidney; however, at high doses the excretion rate of the contralateral kidney was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnston
P A
PA
Department of Pharmacology, ICI Americas Pharmaceuticals Group, ICI Americas, Inc., Wilmington, DE.
Zuzack
J S
JS
Pritchard
W J
WJ
Kau
S T
ST
D000818:Animals; D001682:Biological Availability; D004232:Diuretics / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012077:Renal Artery
D004232:Diuretics