The direct renin inhibitor aliskiren localizes and persists in rat kidneys.

The direct renin inhibitor aliskiren localizes and persists in rat kidneys. Am J Physiol Renal Physiol. 2013 Aug 7; Authors: Feldman DL, Jin L, Xuan H, Persohn E, Zhou W, Schuetz H, Park JK, Mueller DN, Luft FC Abstract The aims of this study were to 1) determine whether renal localization of aliskiren and its anti-hypertensive and renoprotective effects persist after stopping administration of the drug, and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg/kg/day sc; osmotic minipumps) or enalapril (18mg/L in drinking water). After 2 weeks treatment dTGR were assigned to either continued treatment with aliskiren ("continued"), or to cessation of their respective treatment ("stopped") for three weeks washout. One week treatment with aliskiren and enalapril reduced BP and albuminuria vs baseline. After cessation of either treatment, blood pressure had returned to pre-treatment levels and albuminuria remained relatively low for 1 week, but rose thereafter similarly in both groups. In contrast, renal mRNA for TGF-β and renal collagen IV was reduced by aliskiren (continued and stopped groups), but not after cessation of enalapril. Similar patterns were found for collagen IV protein expression. Even 3 weeks after stopping aliskiren treatment, renal levels of the drug exceeded...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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