Abstract 16955: The Direct Renin Inhibitor Aliskiren Improves Vascular Remodeling in Transgenic Rats Harboring Human Renin and Angiotensinogen Genes
The renin inhibitor aliskiren (ALK) reduces blood pressure and improves cardio-renal organ damage in hypertensive double transgenic rats (dTGRs) which express both human renin and angiotensinogen. Little is known about the effect of ALK on hypertension-related vascular structural alterations of resistance arteries. We tested the hypothesis that chronic treatment with ALK improves vascular remodeling of resistance arteriesin in dTGR. dTGRs (5 weeks old) were treated with ALK (3 mg/kg/day, n=5) or ramipril (RAM, 1 mg/kg/day, n=5) for 14 days and compared with age-matched untreated dTGRs. Blood pressure (BP) was measured by tail-cuff method. Resistance arteries media-to-lumen ratio (M/L) was evaluated on mesenteric arteries as pressurized preparations. The expression of AT1 receptor, AT2 receptor, eNOS and the NADPH subunit gp91phox was evaluated in aorta by immunoblotting. The reactive oxygen species (ROS) production was evaluated in aorta by Dihydroethidium (DHE) staining. BP was similarly reduced in both ALK-treated and RAM-treated rats compared to untreated dTGRs (167±1.18 mmHg and 169.4±1.5 mmHg vs 196.8 ±3.9 mmHg, respectively P<0.05; reduction of -15% and -14%; P<0.05). M/L was equally reduced in ALK-treated and RAM-treated rats compared to untreated rats (6.3±0.5 % and 6.4±0.2 % vs 9.8±.04%, respectively; P<0.05). AT1 and AT2 receptor expression was similar in all the groups. eNOS expression was increased only in ALK-treated rats (+41.3±6.3 % vs untreated dTGRs, p<0.05). gp91phox was slightly reduced in both ALK-and RAM-treated dTGRs. Both ALK and RAM similarly reduced ROS production in dTGRs compared to untreated rats (14.7±0.2 AU and 13.9±0.3 AU vs 18.1±0.9 AU, respectively; p<0.05). In conclusion equieffective antihypertensive dose of ALK or RAM improved oxidative stress and reduced M/L of mesenteric arteries. Only ALK increased the eNOS bioavailability. Hence, in dTGRs renin inhibition compares favorably to ACE inhibition in improving vascular remodeling.
- © 2011 by American Heart Association, Inc.