Artikel
Aliskiren, a human renin inhibitor, reverses cardiac and renal damage in double-transgenic rats
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Veröffentlicht: | 10. August 2005 |
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We tested the hypothesis that Aliskiren reverses organ damage in rats transgenic for human renin and angiotensinogen genes (dTGR). Six week-old dTGR were matched by albuminuria (2 mg/d) and divided in 5 groups. Untreated dTGR were compared with Aliskiren (3 and 0.3mg/kg/d by mini pumps) and valsartan (Val 10 and 1 mg/kg/d in the diet). Treatment was week 6 through 9. At week 6, all groups had elevated systolic blood pressure (BP). Aliskiren promptly lowered BP (115±6 and 139±5 mm Hg; p<0.05) and albuminuria (0.4±0.1 and 1.6±0.6 mg/d; p<0.05) at both doses. Untreated dTGR showed increased BP (202±4 mm Hg) and albuminuria (34±5.7 mg/d) at week 7. While high dose Val lowered BP (148±4 mm Hg) and albuminuria (2.1±0.7 mg/d) similarly compared to Aliskiren (0.3mg/kg/d), low dose Val reduced BP (182±3 mm Hg) and albuminuria (24±3.8 mg/d) slightly. By week 9, 100% (19/19) untreated dTGR died, whereas only 26% (5/19) of the Val (1 mg/kg/d), and no rat in the other groups died. At week 9, low dose Val barely kept dTGR alive. The rats had cardiac hypertrophy (4.4±0.1 mg/g), increased left ventricular (LV) wall thickness, signs of diastolic dysfunction (E<A), increased LV atrial natriuretic peptide, and b-myosin heavy chain mRNA expression, reduced a-myosin heavy chain mRNA expression, albuminuria (24±4 mg/d), renal and cardiac fibrosis, and inflammatory cell infiltration in kidney and heart. In contrast, both Aliskiren doses and high-dose Val lowered BP, albuminuria, cardiac, and renal damage. Direct renin inhibition offers an attractive alternative in reversing Ang II-induced organ damage.