title: The effect of valsartan on the angiotensin II pressor response in healthy normotensive male subjects.
abstract: OBJECTIVE
  Valsartan is an oral antagonist of angiotensin II that competes with angiotensin II for the AT1-receptor and is being developed as an antihypertensive agent. This study assessed the ability of 80 mg valsartan to inhibit the pressor effect of exogenous angiotensin II in healthy normotensive men, first after a single dose and then after multiple doses once daily for 7 days.
  
  
  METHODS
  This was a single-center, double-blind, placebo-controlled, randomized crossover study. Six healthy men underwent angiotensin II challenges to determine a suitable dose required to increase their systolic blood pressure by approximately 30 mm Hg. Each subject then received an 80 mg dose of valsartan or matching placebo. The inhibition of the angiotensin II pressor effect was determined by the systolic blood pressure response to repeated angiotensin II challenges at multiple time points.
  
  
  RESULTS
  Systolic blood pressure responses to angiotensin II challenges after single and multiple doses of valsartan were significantly lower than placebo, indicating that valsartan blocked the blood pressure response to angiotensin II. The maximum blocking effect was observed within 2 to 3 hours. Mean data suggested that differences in effect between valsartan and placebo were similar after both single and multiple doses and persisted up to 24 hours after administration. The angiotensin II blocking effect was maintained up to this time, despite low plasma valsartan levels and minimal accumulation after multiple doses.
  
  
  CONCLUSIONS
  Valsartan, 80 mg, is a potent angiotensin II antagonist with a rapid onset of action and persistent angiotensin II inhibition up to 24 hours. There is no attenuation of this effect after multiple doses.
authors.affiliation: Department of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19129, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Morgan
authors.forename: M
authors.initials: M
authors.lastname: Palmisano
authors.forename: A
authors.initials: A
authors.lastname: Piraino
authors.forename: W
authors.initials: W
authors.lastname: Hirschhorn
authors.forename: S
authors.initials: S
authors.lastname: Spencer
authors.forename: P P
authors.initials: PP
authors.lastname: Prasad
authors.forename: M
authors.initials: M
authors.lastname: Ortiz
authors.forename: P
authors.initials: P
authors.lastname: Lloyd
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D016014:Linear Models; D008297:Male; D011945:Receptors, Angiotensin / Q000187:drug effects*; D012016:Reference Values; D013777:Tetrazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine