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

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Item Type:	Article
Title:	Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats
Creators Name:	Pilz, B., Shagdarsuren, E., Wellner, M., Fiebeler, A., Dechend, R., Gratze, P., Meiners, S., Feldman, D.L., Webb, R.L., Garrelds, I.M., Danser, A.H.J., 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
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	46
Number:	3
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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