Calcium blockade versus ACE inhibition in clipped and unclipped kidneys of 2K-1C rats.
ACE inhibitors have been shown to worsen the kidney damage occurring distal to a renal artery stenosis. To determine if this effect was due to the decrease of arterial pressure or to an inhibition of the formation of angiotensin, we compared the effects of equihypotensive doses of an angiotensin converting enzyme inhibitor (enalapril) and a long-acting calcium antagonist (Ro 40-5967) in 2K-1C rats. The rats were treated for five weeks with either enalapril, Ro 40-5967, or were left untreated. A group of sham operated rats was used as control. At the end of the five-week treatment period, proteinuria, plasma urea and creatinine were measured and quantitative morphometry of the clipped and unclipped kidneys was performed. Ro 40-5967, despite an absence of inhibition of the renin-angiotensin system, worsened the lesions of the clipped kidney to the same extent as enalapril. In contrast, the effects of both drugs on the unclipped kidney were different. Ro 40-5967, and not enalapril, increased the weight and the glomerular surface area of the unclipped kidney. Ro 40-5967 did not change the glomerulosclerosis index, which was improved by enalapril. In contrast with enalapril, Ro 40-5967 decreased plasma urea and creatinine concentrations. Only enalapril decreased proteinuria which originated from the unclipped kidney as shown by nephrectomy experiments. We conclude that during ACE inhibition the fall in renal perfusion pressure seems to be the main determinant of the renal damage distal to a renal artery stenosis, independently of a blockade of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
M
M
Véniant
D
D
Heudes
J P
JP
Clozel
P
P
Bruneval
J
J
Ménard
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D003404:Creatinine / Q000097:blood; D006978:Hypertension, Renovascular / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D020748:Mibefradil; D009392:Nephrectomy; D009929:Organ Size; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012078:Renal Artery Obstruction / Q000473:pathology / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014508:Urea / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D014508:Urea; D003404:Creatinine