Consequences of renal morphologic damage induced by inhibition of converting enzyme in rat renovascular hypertension.
The consequences of morphologic changes in the kidney distal to a stenosis induced by chronic administration of a converting enzyme inhibitor were determined after induction of experimental renovascular hypertension in rats. The relationship between changes in morphology in the clipped kidney and diuresis, creatinine, and mortality was studied by converting a two-kidney, one-clip model into a one-kidney, one-clip model after 1 month of converting enzyme inhibition. The right renal artery was constricted with a clip of 0.2 mm diameter to increase blood pressure, the left kidney was left untouched. After 1 month, systolic blood pressure had increased to 173 +/- 27 mm Hg in the clipped animals (n = 47) compared with 139 +/- 8 mm Hg in sham-operated animals (n = 15; group 1). An inhibitor of angiotensin-converting enzyme, MK421 (2 mg/kg, po), or an equivalent volume of vehicle was then administered daily for 1 month. After treatment with the converting enzyme inhibitor, blood pressure (148 +/- 28 mm Hg) was virtually identical with that of a sham-operated, vehicle-treated control group (145 +/- 16 mm Hg, n = 15), and was significantly lower than that of untreated hypertensive rats (186 +/- 30 mm Hg, n = 17) (group 2). The weight of the left kidney was increased in the untreated hypertensive animals as compared with sham-operated controls (1260 +/- 168 mg for group 2 versus 1075 +/- 100 mg for group 1). After treatment with MK421, the weight of the contralateral kidney (1472 +/- 190 mg) was further increased. After 1 month of treatment with MK421 or vehicle, the unclipped left kidney was removed from all animals. The treated animals were then randomly divided into two groups: one in which treatment with MK421 was stopped (treated/untreated, n = 24; group 3) and a second in which the treatment was continued (treated/treated, n = 23; group 4). The ability of the rats to excrete a water load of 15 ml was then examined 12 hours after removal of the unclipped left kidney. In the two groups of treated rats, the urinary excretion of the water load was decreased and frequency of oliguria was increased as compared with controls and hypertensive untreated rats. Survival rates were affected by the treatment: 3 deaths occurred in the hypertensive untreated group 2, 10 in the treated/untreated group 3, and 12 in the treated/treated group 4. The majority of these deaths could be attributed to renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
Michel
J B
JB
Unité 36, Institut National de la Santé et de la Recherche Médicale 17, Paris.
Nochy
D
D
Choudat
L
L
Dussaule
J C
JC
Philippe
M
M
Chastang
C
C
Corvol
P
P
Menard
J
J
D000818:Animals; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013722:Teprotide
D009842:Oligopeptides; D003404:Creatinine; D013722:Teprotide