title: Angiotensin II-receptor antagonist losartan does not prevent nitroglycerin tolerance in patients with coronary artery disease.
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 AT(1) antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.
authors.affiliation: Division of Cardiology, Fondazione Salvatore Maugeri, IRCCS Scientific Institute of Telese Terme, Via Bagni Vecchi, 82037 Telese Termi, Italy. glongobardi@fsm.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Longobardi
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferrara
authors.forename: Dario
authors.initials: D
authors.lastname: Leosco
authors.forename: Pasquale
authors.initials: P
authors.lastname: Abete
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Furgi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cacciatore
authors.forename: Graziamaria
authors.initials: G
authors.lastname: Corbi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pescatore
authors.forename: Franco
authors.initials: F
authors.lastname: Rengo
mesh_terms: D000279:Administration, Cutaneous; D000787:Angina Pectoris / Q000188:drug therapy*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004361:Drug Tolerance; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D014665:Vasodilator Agents; D005996:Nitroglycerin; D019808:Losartan