title: Hormonal and hemodynamic effects of aliskiren and valsartan and their combination in sodium-replete normotensive individuals.
abstract: OBJECTIVE
  An AT1 receptor antagonist induces a counterregulatory renin release whose intensity and duration reflect the magnitude of the renin-angiotensin blockade. We investigated whether a renin inhibitor may neutralize this counterregulation and amplify the effects of AT1 receptor antagonists.
  
  
  METHODS
  In 12 normotensive male individuals who were on a high-sodium diet, a double-blind, placebo-controlled, randomized, crossover design was used to study the hormonal and BP effects of single oral administrations of 300 mg of the renin inhibitor aliskiren, 320 mg of valsartan, and a combination of these two drugs, each at half dosage (150 mg of aliskiren and 160 mg of valsartan).
  
  
  RESULTS
  Valsartan (320 mg) increased plasma renin activity and angiotensin I and angiotensin II levels, but 300 mg of aliskiren decreased them for 48 h. Aliskiren (300 mg) stimulated immunoreactive renin release more strongly than 320 mg of valsartan, decreased urinary aldosterone excretion for longer than 320 mg of valsartan, and had a similar BP-lowering effect as 320 mg of valsartan. In combination, 150 mg of aliskiren neutralized the valsartan (160 mg)-induced increase in plasma angiotensins for 48 h. The renin and aldosterone effects of the combination of 150 mg of aliskiren and 160 mg of valsartan were similar to those of 300 mg of aliskiren and greater than those of 320 mg of valsartan. When plasma drug concentrations were taken into account, the combination of 150 mg of aliskiren and 160 mg of valsartan had a synergistic effect on renin release. The BP-lowering effect of 150 mg of aliskiren and 160 mg of valsartan was similar to that of 300 mg of aliskiren and 320 mg of valsartan at peak but was more prolonged.
  
  
  CONCLUSIONS
  The stronger and longer lasting effects on plasma active renin and urinary aldosterone of aliskiren, alone or in combination, demonstrate a more effective blockade of the renin-angiotensin system than that obtained with 320 mg of valsartan alone.
authors: Université Paris Descartes, Faculté de Médecine, Paris, France. michel.azizi@egp.ap-hop-paris.fr
authors: Michel
authors: M
authors: Azizi
authors: Joël
authors: J
authors: Ménard
authors: Alvine
authors: A
authors: Bissery
authors: Than-Tam
authors: TT
authors: Guyene
authors: Alessandra
authors: A
authors: Bura-Rivière
mesh_terms: D000328:Adult; D000577:Amides / Q000493:pharmacokinetics / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D012964:Sodium / Q000378:metabolism*; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000068756:Valsartan; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D005650:Fumarates; D012964:Sodium; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000092502:Renin Inhibitors; C446481:aliskiren