doi: 10.1161/hc3601.095576
(Circulation. 2001;104:1436.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension
Relation to Kidney Inflammation
From the Department of Medicine IV, University of Erlangen, Nürnberg (K.F.H., A.H., M.P., R.V.); the Department of Medicine VI, Schwabing General Hospital, Ludwig-Maximilians-University, Munich (J.F.E.M.); and the German Institute for High Blood Pressure Research, Heidelberg (K.F.H., R.V., J.F.E.M.), Germany.
Reprint requests to Karl F. Hilgers, MD, Nephrology Research Laboratory, Loschgestrasse 8, D-91054 Erlangen, Germany. E-mail karl.hilgers{at}rzmail.uni-erlangen.de
Background—— Angiotensin II is elevated in malignant hypertension. We tested the hypothesis that angiotensin II type 1 receptor blockade can prevent the development of malignant hypertension even in the absence of a blood pressure-lowering effect.
Methods and Results—— Two-kidney, 1-clip rats were followed up for 28 days; blood pressure was measured by tail-cuff plethysmography and intra-arterially. After a 2-week run-in phase, rats received valsartan at a dose of 0.3 (n=14) or 3 (n=12) mg · kg-1 · d-1 or solvent (n=27). Only the higher dose of valsartan, but not the lower dose, decreased blood pressure. Both doses of valsartan prevented the development of lethal malignant hypertension. Twenty of 27 solvent-treated renovascular hypertensive rats died, but only 3 of 14 rats treated with the low dose and 1 of 12 rats treated with the high dose of valsartan died. Histological signs of malignant nephrosclerosis were found in all rats examined that had died throughout the study and in 6 of 7 surviving solvent-treated renovascular hypertensive animals. Increased expression of monocyte chemoattractant protein-1 and prominent interstitial influx of macrophages occurred in the nonclipped kidneys exposed to high pressure in solvent-treated rats. These alterations were prevented by valsartan at both doses, irrespective of blood pressure effects.
Conclusions—— Angiotensin II type 1 receptor blockade by valsartan prevents lethal malignant hypertension independently of blood pressure. The results suggest that reduction of angiotensin-induced inflammation in the kidney may contribute to the protective effects of valsartan.
Key Words: angiotensin • hypertension • kidney • leukocytes • survival
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