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 d istal to a renal artery stenosis. To determine if this effect was due to the decrease of arterial pressure or to an inhibition of the format ion of angiotensin, we compared the effects of equihypotensive doses o f an angiotensin converting enzyme inhibitor (enalapril) and a long-ac ting calcium antagonist (Ro 40-5967) in 2K-1C rats. The rats were trea ted for five weeks with either enalapril, Ro 40-5967, or were left unt reated. A group of sham operated rats was used as control. At the end of the five-week treatment period, proteinuria, plasma urea and creati nine were measured and quantitative morphometry of the clipped and unc lipped kidneys was performed. Ro 40-5967, despite an absence of inhibi tion of the renin-angiotensin system, worsened the lesions of the clip ped kidney to the same extent as enalapril. In contrast, the effects o f both drugs on the unclipped kidney were different. Ro 40-5967, and n ot 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, R o 40-5967 decreased plasma urea and creatinine concentrations. Only en alapril decreased proteinuria which originated from the unclipped kidn ey as shown by nephrectomy experiments. We conclude that during ACE in hibition the fall in renal perfusion pressure seems to be the main det erminant of the renal damage distal to a renal artery stenosis, indepe ndently of a blockade of the renin-angiotensin system. However, pharma cological effects other than the decrease of arterial pressure play an important role in the unclipped kidney.