卡托普利增强硝酸酯类药物对冠心病心衰疗效的研究

A STUDY OF CAPTOPRIL ENHANCEMENT OF NITRATE EFFECT CORONARY ARTERIAL DISEASE PATIENTS ASSOCIATED WITH HEART FAILURE

急性心肌梗塞并急性左心衰者静滴硝酸甘油３日及心绞痛并充血性心衰者服消心痛３周后，其初始的血流动力学效应及抗心绞痛作用递减，伴血管紧张素ＩＩ（ＡＩＩ）及体重增多。合用卡托普利者疗效明显提高且持久，ＡＩＩ及体重下降。消心痛预处理离休鼠心灌汪卡托普利加硝酸甘油后冠脉流量显著高于单用两药；灌注依那普利加硝酸甘油无此作用。提示补充巯基及对抗神经－激素激活可能是卡托普利增强硝酸酯疗效的机制。

It is shown in a prospective study that the initial beneficial hemodynamic effect of nitroglyeerine(NTG)significantly decreased after continuous 3-day infusion of this drug(10～50μg/ min)in acute myocardial infarction(AMI) patients associated with acute left heart failure,The effect of ameliorating anginapectoris and improving heart function with isosorbide dinitrate(ISDN) gradually decreased al-most to pretreatment levels after oral administration of this drug (10～20mg, 4 times daily)for 3 weeks in anginapectoris patients associated with congestive heart failure(CHF)with accompanying increased level of plasma angiotensin II(AII) and body weight However,when captopril(CPT, 12.5～25mg,3 times daily)was combined with nitrates,the clinical effects were enhanced and maintained throughout the study,along with a decrease in the level of AII and body weight.In the hearts of rats perfused with CPT and NTG,the coronary flow(CF) significantly increased as compared with the flow when either drng was used alone.Enelapril(ENL,a non-sulfhydryl drug),however,did not show such effect. The above results indicate that repletion of sulfhydryl to vascular smooth muscle and antineurohumoral activation may be the potential mechanisms by which CPT reverses nitrate toleranee and enhances its clinical effects.