Continuous versus intermittent angiotensin converting enzyme inhibition in renal hypertensive rats.
Converting enzyme inhibitors impair renal function of the kidney beyond a stenosis of the renal artery in humans and induce histological lesions in the clipped kidney of renal hypertensive rats. In two-kidney, one clip hypertensive rats, we compared the time course and magnitude of the biochemical effects of angiotensin converting enzyme inhibition on the plasma renin-angiotensin system, cardiac hypertrophy, renal lesions, and 24-hour blood pressure decrease induced by either intermittent angiotensin converting enzyme inhibition administration (benazepril PO, 10 mg/kg once a day, n = 93) or continuous administration (benazeprilat, 3 mg/kg per day via osmotic pumps, n = 92). Control rats (n = 91) received the drug vehicle intermittently or continuously. Mortality was significantly reduced by both intermittent (n = 3/93) and continuous (n = 3/92) inhibition compared with controls (n = 18/91) (P < .001). Changes in the plasma renin-angiotensin system and blood pressure were parallel. A continuous suppression of the activity of the plasma renin-angiotensin system was associated with a 24-hour decrease in blood pressure with continuous inhibition, whereas intermittent inhibition induced a similar fall in blood pressure only for the first hours after gavage.(ABSTRACT TRUNCATED AT 250 WORDS)
Battle
T
T
Cardiovascular Research, CIBA-GEIGY Ltd., Basel, Switzerland.
Schnell
C
C
Bunkenburg
B
B
Heudes
D
D
Wood
J M
JM
Ménard
J
J
D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D014508:Urea / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000804:Angiotensin II; D014508:Urea; D003404:Creatinine; D012083:Renin; C044946:benazepril