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Nephrol Dial Transplant (1992) 7: 602-607
© 1992 European Renal Association-European Dialysis and Transplant Association

research-article

Acute renal vascular response to ACE inhibition in two rat strains with different susceptibility to the development of glomerulosclerosis

P. J. Westenend1,, J. F. M. Smits2, H. A. J. Struyker-Boudier2 and J. J. Weening3

1Department of Pathology, State University Leiden 2Department of Pharmacology, State University Maastricht 3Department of Pathology, University of Amsterdam The Netherlands

Correspondence and offprint requests to: Correspondence and offprint request to: Pieter J. Westenend, MD, Department of Pathology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands

Normotensive male Wistar rats are susceptible to the development of glomerulosclerosis, a process which can be accelerated by partial renal ablation, while normotensive male Wistar Kyoto (WKy) rats are resistant to glomerulosclerosis. Longterm treatment with angiotensin-I-converting enzyme inhibitors prevents the development of glomerulosclerosis. We studied the acute renal vascular response to bolus injections of captopril (1, 3, and 10mg/kg). Mean arterial blood pressure (MAP) was significantly less in Wistar rats compared to WKy and not influenced by unilateral nephrectomy. Renal vascular resistance (RVR) and the filtration fraction (FF) were significantly greater in sham and unilateral nephrectomy Wistar rats as compared to WKy. Captopril significantly reduced the RVR in all four groups, but at comparable doses, RVR remained greater in the Wistar sham and Wistar rats following unilateral nephrectomy compared to sham and uninephrectomized WKy respectively. Captopril reduced FF in Wistar rats only. These data indicate an enhanced level of activity of the renal renin-angiotensin system in glomerulosclerosis-susceptible Wistar rats compared to glomerulosclerosis-resistant WKy rats, suggesting that vascular reactivity involving the renin-angiotensin system is an important determinant of the genetically determined differences in susceptibility to glomerulosclerosis in these two rats strains. The strain-dependent difference in RVR at the highest dose of captopril indicates that additional, possibly structural features may play a role in the difference in susceptibility to glomerulosclerosis.

Keywords: angiotensin-converting enzyme inhibition; glomerulosclerosis; rat; renal haemodynamics


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