Kf. Hilgers et al., Angiotensin II type 1 receptor blockade prevents lethal malignant hypertension - Relation to kidney inflammation, CIRCULATION, 104(12), 2001, pp. 1436-1440
Citations number
30
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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 press
ure-lowering effect.
Methods and Results-Two-kidney, 1-clip rats were followed up for 28 days, b
lood pressure was measured by tail-cuff plethysmography and intra-arteriall
y. 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 hype
rtension. 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 w
ith the high dose of valsartan died. Histological signs of malignant nephro
sclerosis were found in all rats examined that had died throughout the stud
y 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 expos
ed to high pressure in solvent-treated rats. These alterations were prevent
ed by valsartan at both doses, irrespective of blood pressure effects.
Conclusions-Angiotensin II type I receptor blockade by valsartan prevents l
ethal malignant hypertension independently of blood pressure. The results s
uggest that reduction of angiotensin-induced inflammation in the kidney may
contribute to the protective effects of valsartan.