Chronic angiotensin converting enzyme inhibition in the two-kidney, one clip hypertensive rat. 1988

B Jackson, and L Franze, and E Sumithran, and C Johnston
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.

Treatment with an angiotensin converting enzyme (ACE) inhibitor in renovascular hypertension produces acute effects on renal function; however, the long-term consequences of this are not known. We have studied the effect of chronic enalapril treatment on renal structure and function in the two-kidney, one clip model of renovascular hypertension in the rat. Four weeks after the left renal artery was clipped, the hypertensive rats were randomly allocated to treatment with enalapril, minoxidil or to no treatment. The drug dose was titrated for maximal hypotensive effect. After 4 months of treatment blood pressures were 129 +/- 3 mmHg (enalapril), 193 +/- 5 mmHg (minoxidil) and 220 +/- 4.8 mmHg (no treatment). Twelve months later survival was 84% (enalapril group), 48% (minoxidil group) and 15% (untreated group). Split kidney function (51Cr-EDTA clearance, ml/min) of the clipped kidneys was 0.0 (enalapril group), 0.26 +/- 0.23 (minoxidil group) and 0.74 +/- 0.13 (untreated group). The clipped kidney from enalapril-treated rats weighed 0.46 +/- 0.1 g, much less than in the minoxidil-treated group (1.2 +/- 0.07) or the untreated group (1.14 +/- 0.10). Enalapril treatment was withdrawn for 2 weeks in five rats, but the clipped kidney remained small and non-functional. Histological examination revealed marked interstitial fibrosis and tubular atrophy in clipped kidneys from both enalapril groups, in contrast to minor changes in the minoxidil-treated and the untreated groups. We conclude that chronic enalapril treatment of two-kidney, one clip hypertension in the rat improved survival and preserved total renal function, but was associated with irreversible fibrotic atrophy of the clipped kidney.

UI MeSH Term Description Entries
D006978 Hypertension, Renovascular Hypertension due to RENAL ARTERY OBSTRUCTION or compression. Hypertension, Goldblatt,Goldblatt Syndrome,Goldblatt Hypertension,Renovascular Hypertension,Syndrome, Goldblatt
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008914 Minoxidil A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371) Loniten,Regaine,Rogaine,U 10858
D004656 Enalapril An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE. Enalapril Maleate,MK-421,MK421,Renitec,Renitek,MK 421,Maleate, Enalapril
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D000806 Angiotensin-Converting Enzyme Inhibitors A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. ACE Inhibitor,ACE Inhibitors,Angiotensin Converting Enzyme Inhibitor,Angiotensin I-Converting Enzyme Inhibitor,Angiotensin-Converting Enzyme Inhibitor,Kininase II Inhibitor,Kininase II Inhibitors,Angiotensin I-Converting Enzyme Inhibitors,Angiotensin-Converting Enzyme Antagonists,Antagonists, Angiotensin-Converting Enzyme,Antagonists, Kininase II,Inhibitors, ACE,Inhibitors, Angiotensin-Converting Enzyme,Inhibitors, Kininase II,Kininase II Antagonists,Angiotensin Converting Enzyme Antagonists,Angiotensin Converting Enzyme Inhibitors,Angiotensin I Converting Enzyme Inhibitor,Angiotensin I Converting Enzyme Inhibitors,Antagonists, Angiotensin Converting Enzyme,Enzyme Antagonists, Angiotensin-Converting,Enzyme Inhibitor, Angiotensin-Converting,Enzyme Inhibitors, Angiotensin-Converting,II Inhibitor, Kininase,Inhibitor, ACE,Inhibitor, Angiotensin-Converting Enzyme,Inhibitor, Kininase II,Inhibitors, Angiotensin Converting Enzyme
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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