title: Effect of angiotensin II receptor antagonist and endothelin receptor antagonist on nitroglycerin tolerance in rats.
abstract: OBJECTIVE
  To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo.
  
  
  METHODS
  Twenty-four rats were divided into 4 groups (n = 6, each): Control group, Nitroglycerin (Nit) group, Nit + bosentan group and Nit + losartan group. Nitroglycerin tolerance was induced by 2-day treatment of (10 mg x kg(-1) nitroglycerin patch(0.05 mg/h). Angiotensin receptor antagonist losartan(10 mg x kg(-1) x d(-1)) and endothelin receptor antagonist bosentan (100 mg x kg(-1) x d(-1)) were given by gavage for 2 days respectively.
  
  
  RESULTS
  The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group. The effective percentages of hypotensive response to SNP were increased in both Nit + losartan group and Nit + bosentan group compared with Nit group [(31.95 +/- 4.45) % vs (21.00 +/- 3.69) %, P < 0.01 and (33.18 +/- 6.16) % vs (21.00 +/- 3.69) %, P < 0.01, respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response to SNP) was found in tolerant group[(34 +/- 10) nmol/L, P < 0.01]. The ET-1 amounts in plasma and vascular tissue were markedly increased by 54% and 60% in Nit group compared with those in control group( P < 0.01). The ET-1 amounts in plasma and vascular tissue were decreased by 30% and 37% in Nit + losartan group compared with those in Nit group (P < 0.01).
  
  
  CONCLUSIONS
  Endothelin receptor antagonist and angiotensin II receptor antagonist could prevent against the Nit tolerance.
authors.affiliation: Department of Pediatrics, First Hospital of Peking University, Beijing 100034.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Tang
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077300:Bosentan; D004361:Drug Tolerance; D065128:Endothelin Receptor Antagonists; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014665:Vasodilator Agents; D005996:Nitroglycerin; D019808:Losartan; D000077300:Bosentan