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Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats

Item Type:Article
Title:Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats
Creators Name:Pilz, B. and Shagdarsuren, E. and Wellner, M. and Fiebeler, A. and Dechend, R. and Gratze, P. and Meiners, S. and Feldman, D.L. and Webb, R.L. and Garrelds, I.M. and Danser, A.H.J. and Luft, F.C. and Mueller, D.N.
Abstract:We tested the hypothesis that the renin inhibitor aliskiren ameliorates organ damage in rats transgenic for human renin and angiotensinogen genes (double transgenic rat [dTGR]). Six-week-old dTGR were matched by albuminuria (2 mg per day) and divided into 5 groups. Untreated dTGR were compared with aliskiren (3 and 0.3 mg/kg per day)-treated and valsartan (Val; 10 and 1 mg/kg per day)-treated rats. Treatment was from week 6 through week 9. At week 6, all groups had elevated systolic blood pressure (BP). Untreated dTGR showed increased BP (202±4 mm Hg), serum creatinine, and albuminuria (34±5.7 mg per day) at week 7. At week 9, both doses of aliskiren lowered BP (115±6 and 139±5 mm Hg) and albuminuria (0.4±0.1 and 1.6±0.6 mg per day) and normalized serum creatinine. Although high-dose Val lowered BP (148±4 mm Hg) and albuminuria (2.1±0.7 mg per day), low-dose Val reduced BP (182±3 mm Hg) and albuminuria (24±3.8 mg per day) to a lesser extent. Mortality was 100% in untreated dTGR and 26% in Val (1 mg/kg per day) treated rats, whereas in all other groups, survival was 100%. dTGR treated with low-dose Val had cardiac hypertrophy (4.4±0.1 mg/g), increased left ventricular (LV) wall thickness, and diastolic dysfunction. LV atrial natriuretic peptide and β-myosin heavy chain mRNA, albuminuria, fibrosis, and cell infiltration were also increased. In contrast, both aliskiren doses and the high-dose Val lowered BP to a similar extent and more effectively than low-dose Val. We conclude that in dTGR, equieffective antihypertensive doses of Val or aliskiren attenuated end-organ damage. Thus, renin inhibition compares favorably to angiotensin receptor blockade in reversing organ damage in dTGR.
Keywords:Hypertrophy, Renin, Transgenic Rats, Animals, Rats
Publisher:American Heart Association
Page Range:569-576
Date:15 August 2005
Official Publication:https://doi.org/10.1161/01.HYP.0000179573.91016.3f
PubMed:View item in PubMed

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