Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/lipid metabolism in obese patients with hypertension
Aliskiren penetrates adipose and skeletal muscle in hypertensive patients with abdominal obesity and reduces renin–angiotensin–aldosterone system activity. After discontinuation, blood pressure–lowering effects are observed possibly through drug–tissue binding. We performed microdialysis evaluation of adipose tissue and skeletal muscle before and during an insulin-modified frequently sampled intravenous glucose tolerance test (IM-FSIGT). Aliskiren 300 mg (n = 8) or amlodipine 5 mg (n = 8) once daily were administered during a 12-week randomized treatment period. Aliskiren elicited variable changes in median interstitial angiotensin II (Ang II) in adipose (2.60–1.30 fmol/mL) and skeletal muscle (2.23–0.68 fmol/mL); amlodipine tended to increase adipose and skeletal muscle Ang II (P =.066 for skeletal muscle treatment difference). Glucose/insulin increased median plasma Ang II 1 hour after glucose injection (1.04–2.50 fmol/mL; P =.001), which was markedly attenuated by aliskiren but not amlodipine. Aliskiren increased glucose disposition index (P =.012) and tended to increase acute insulin response to glucose (P =.067). Fasting adipose glycerol (−17%; P =.064) and fasting muscle glucose dialysate (−17%; P =.025) were decreased by aliskiren but not amlodipine. In summary, aliskiren decreased Ang II production in response to glucose/insulin stimulus and elicited metabolic effects in adipose and skeletal muscle suggestive of increased whole-body glucose utilization.
|Keywords||Adipose tissue, amlodipine, angiotensin II, insulin sensitivity, microdialysis, obesity, plasma renin activity, skeletal muscle|
|Persistent URL||dx.doi.org/10.1016/j.jash.2017.06.002, hdl.handle.net/1765/108683|
|Journal||American Society of Hypertension. Journal|
Engeli, S, May, M. (Marcus), Nussberger, J, Danser, A.H.J, Dole, W.P, Prescott, M.F. (Margaret F.), … Jordan, J. (2017). Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/lipid metabolism in obese patients with hypertension. American Society of Hypertension. Journal, 11(8), 488–497. doi:10.1016/j.jash.2017.06.002