EFFECT
OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON
NITROGLYCERIN TOLERANCE IN RATS
Zhang Jianmei1, Chen Yonghong1,
Wang Xiaohong2, Tang Chaoshu2
Department
of Pediatrics1, Institute of Cardiovascular Research2,
The First Hospital of Peking University, Beijing, China
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/d) and endothelin receptor antagonist bosentan (100
mg/kg/d ) 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 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 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.