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 nitroglycerin patch （0.05 mg/h）. AngiotensinⅡ receptor antagonist losartan （ 10 mg· kg－ 1· d－ 1 ） and endothelin receptor antagonist bosentan （ 100 mg· kg－ 1· 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）. Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .