Dose-dependent blockade of the angiotensin II type 1 receptor with losartan in normal volunteers

Michael S. Berlowitz, Farhana Latif, Shelley R. Hankins, Pierre Vladimir Ennezat, Robert Moskowitz, Suman Tandon, Paolo C. Colombo, Thierry H. Le Jemtel

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Abstract

Losartan, an angiotensin II type 1 receptor (AT1) antagonist, was developed as a more specific alternative to angiotensin-converting enzyme (ACE) inhibitors. At a daily dose of 50 mg, losartan is currently evaluated in large outcome trials involving patients with hypertension and postmyocardial infarction. The current study evaluated the level and duration of blockade of a pressor response to angiotensin II by 50 and 150 mg of losartan, compared with 32 mg of candesartan. Eight normotensive volunteers were randomly assigned to a single dose of losartan 50 or 150 mg, candesartan 32 mg, or placebo. Subjects were re-randomized after a 2-week washout period to complete all four study arms. Radial artery systolic pressure response to exogenous angiotensin II was measured at 2, 6, 12, and 24 h after administration of drug. Losartan 50 mg reduced the pressure response to exogenous angiotensin II significantly only at 6 h. In contrast, candesartan and losartan 150 mg produced a greater reduction in the pressure response to angiotensin II throughout the 24-h period. This suppression was not paralleled by a reduction in resting systemic arterial pressure. Higher doses than 50 mg of losartan might be evaluated to elicit optimal clinical effects.

Original languageEnglish (US)
Pages (from-to)692-696
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume37
Issue number6
DOIs
StatePublished - Jun 7 2001

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Berlowitz, M. S., Latif, F., Hankins, S. R., Ennezat, P. V., Moskowitz, R., Tandon, S., Colombo, P. C., & Le Jemtel, T. H. (2001). Dose-dependent blockade of the angiotensin II type 1 receptor with losartan in normal volunteers. Journal of Cardiovascular Pharmacology, 37(6), 692-696. https://doi.org/10.1097/00005344-200106000-00006