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).
Conclusion: Endothelin receptor antagonist and angiotensin II receptor antagonist could prevent against the Nit tolerance.