Hilgers KF, Hartner A, Porst M, Veelken R, Mann J (2007)
Publication Type: Journal article
Publication year: 2007
Book Volume: 104
Pages Range: 1436-1440
Issue: 12
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.
APA:
Hilgers, K.F., Hartner, A., Porst, M., Veelken, R., & Mann, J. (2001). Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension. Circulation, 104, 1436-1440. https://doi.org/10.1161/hc3601.095576
MLA:
Hilgers, Karl Friedrich, et al. "Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension." Circulation 104 (2001): 1436-1440.
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