RENAL MORPHOLOGY AND FUNCTION IN DOGS AFTER TREATMENT WITH THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR QUINAPRIL

Angiotensin-converting enzyme (ACE) inhibitors have proven to be effec tive therapeutic agents for treatment of hypertension and congestive h eart failure (CHF). Because of the role the renin-angiotensin system ( RAS) plays in maintaining renal homeostasis, the effect these compound s have on renal function has been of interest. We assessed the effect of toxicologically significant doses of the new ACE inhibitor, quinapr il, on renal function and morphology in dogs. Groups of 3 male beagle dogs were administered quinapril orally at daily doses of 0, 25, 125, or 250 mg/kg for 13 weeks. After treatment, animals were anesthetized and assessed for clinical pathologic and renal functional disturbances under normal conditions and after volume expansion and diuresis. Rena l histopathology was conducted on perfusion-fixed kidney. No adverse e ffects on sensitive measures of renal function were detected; changes observed were consistent with the pharmacologic consequences of ACE in hibition. Decreased serum Na+ and Cl- (<10%) and hematocrit at 125 and 250 mg/kg, twofold increases in serum creatinine and blood urea nitro gen (BUN) at 250 mg/kg, and decreased arterial blood pressure (BP) (20 %) were observed at all doses. Under baseline conditions, urine flow i ncreased 81-123% in quinapril-treated animals as compared with control s and urine specific gravities decreased 16% relative to controls at 1 25 and 250 mg/kg. Microscopically, juxtaglomerular hypertrophy was obs erved at all doses. At 250 mg/kg, minimal, widely scattered cortical t ubular alterations were observed; glomerular lesions were not. No sign ificant adverse effects of quinapril on renal morphology or function w ere observed at doses similar to 250 times the therapeutic dose.