Abstract 16093: Effects of Aliskiren and Amlodipine Combination Treatment on Endothelial Nitric Oxide and Peroxynitrite Release in Hypertensive Rats
Background: Endothelial cell (EC) dysfunction is causally related to atherosclerosis and hypertension. Aliskiren, a direct renin inhibitor, and amlodipine, a calcium channel blocker, have each been shown to improve vascular function; however, their combined effects are not understood. In this study, we tested the separate versus combined effects of aliskiren and amlodipine on aortic and glomerular EC function.
Methods: Spontaneously hypertensive (SH) rats were assigned to four treatment groups: (1) vehicle; (2) 40 mg/kg/day aliskiren; (3) 5 mg/kg/day amlodipine; and (4) combined aliskiren and amlodipine treatment (at 40 and 5 mg/kg/day, respectively). Each group contained 8 animals and treatments were administered for 8 weeks. Endothelial nitric oxide (NO) and peroxynitrite (ONOO-) release from aortic and glomerular ECs were measured ex vivo using amperometric nanosensors and correlated with systemic blood pressure (BP) measurements.
Results: Aliskiren and amlodipine improved NO release in a manner that was enhanced by combination treatment. Aliskiren alone increased aortic and glomerular NO release by 62% (29 ± 15 to 47 ± 22 nM, p<0.001) and 45% (55 ± 27 to 80 ± 28 nM, p<0.001), respectively, with comparable reductions in ONOO- levels; the NO/ONOO- ratio increased by >2-fold in ECs from either tissue source (p<0.05). Amlodipine increased aortic and glomerular NO release by 237% (to 69 ± 17 nM, p<0.001) and 45% (to 101 ± 16 nM, p<0.001), respectively; the NO/ONOO- ratio increased by >5-fold in cells from either tissue source (p<0.001). Aliskiren/amlodipine combination treatment increased aortic and glomerular NO release by 334% (to 97 ± 11 nM, p<0.001) and 214% (to 118 ± 20 nM, p<0.001), respectively, and increased the NO/ONOO- release ratio by more than 7-fold (p<0.001). Improvements in EC function with these agents were not predicted by changes in BP.
Conclusion: The combination of aliskiren and amlodipine increased aortic endothelial NO release in an enhanced fashion not predicted by BP changes. These findings demonstrate complementary effects of certain antihypertensive agents on EC function.
- © 2011 by American Heart Association, Inc.