Angiotensin II-receptor antagonist Losartan does not prevent nitroglycerin tolerance in patients with coronary artery disease

Giancarlo Longobardi, Nicola Ferrara, Dario Leosco, Pasquale Abete, Giuseppe Furgi, Francesco Cacciatore, Graziamaria Corbi, Raffaella Pescatore, Franco Rengo

Research output: Contribution to journalArticlepeer-review

Abstract

The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo (p <0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in (p <0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p <0.001) or Losartan-placebo (p <0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg (p <0.001, p <0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p <0.001). The AT1 antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume18
Issue number5
DOIs
Publication statusPublished - Sep 2004

Keywords

  • AT antagonist
  • Losartan
  • Nitrate tolerance

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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