阿司匹林与依那普利或氯沙坦合用对兔循环中前列环素、血栓素A_2和去甲肾上腺素的影响

EFFECT OF THE COMBINED ADMINISTRATION OF ASPIRIN WITH EITHER ENALAPRIL OR LOSARTAN ON PROSTACYCLIN THROMBOXONE A_2 AND NOREPINEPHRINE IN RABBIT'S CIRCULATION

通过检测小剂量阿司匹林 (ASA)分别与血管紧张素转换酶抑制剂 (ACEI)或血管紧张素Ⅱ - 1型受体拮抗剂 (ARA)在单用或合用时兔循环中前列环素 (PGI2 )、血栓素A2 (TXA2 )和去甲肾上腺素 (NE)浓度的变化 ,来探讨它们合用时相互作用的问题。方法 :将 6 0只健康新西兰白兔随机分成 6组 ,于连续投药四周前后分别心脏穿刺取血 ,放免法检测PGI2 和TXA2 ,高效液相色谱法检测NE。结果 :不论是单用还是合用 ,A CEI使PGI2 浓度增高 (P <0 .0 5 ,P <0 .0 1) ,小剂量ASA则降低TXA2 浓度 (P <0 .0 5 ,P <0 .0 1) ;ASA与A CEI合用组的PGI2 /TXA2 较其它各组明显升高 (P <0 .0 1) ,血清NE浓度明显下降 (P <0 .0 0 1)。ARA对循环中PGI2 、TXA2 和NE无明显影响。结论 :小剂量ASA和ACEI单用时对兔血清NE浓度无明显影响 ,合用时PGI2 /TXA2 比值上升 ,血清NE浓度下降 ,故二者有协同作用。

Objective:This study was aimed at probing the interaction of the low-dosage of aspirin and either angiotensin-converting enzyme (ACE) inhibitors or angiotensin Ⅱ-1 receptor antagonist (ARA) by detecting prostacyclin (PGI 2), thromboxone A 2(TXA 2) and norepinephrine (NE) in rabbit's circulation when the monotherapy and the combined therapy were used respectively. Methods:Sixty healthy New Zealand rabbits were divided into six groups. Blood samples were drawn from rabbit's heart before and after four-week administration consecutively for four weeks. NE was measured by high performance liquid chromatography, PGI 2 and TXA 2 were measured by radioimmuno-assay. Results:ACE inhibitors increased PGI 2 ( P <0.05, P <0.01), low-dosage of aspirin reduced TXA 2 ( P <0.05, P <0.01) after four-week administration, regardless of the monotherapy and the combined therapy. The combined administration of aspirin with ACE inhibitors augmented PGI 2/TXA 2 ( P <0.01) and then decreased NE significantly in rabbit's circulation ( P <0.001). Conclusions: Low-dosage of aspirin and ACE inhibitors do not influence the concentration of NE in the monotherapy. The ratio of PGI 2 to TXA 2 is increased and NE is decreased significantly in the combined administration of aspirin with ACE inhibitors. We confirm the synergism of the combined administration of aspirin with ACE inhibitors.