硝苯地平与间硝苯地平对美托洛尔撤药后大鼠缺血再灌心肌功能和β受体密度的影响

用离体大鼠心脏灌流模型，观察硝苯地平(Nif)，间硝苯地平(Men)对美托洛尔(Met)连续用药撤药后缺血再灌心功能及心肌β受体密度变化的影响. 缺血再灌使心脏收缩功能降低，心功能曲线压低；左室舒张末压(LVEDP)和心脏压力-容积曲线上抬. Met 50 mg·kg^-1·d^-1 ig，2周，撤药1 d可使缺血再灌心功能略有改善. 按上述Met给药方案，最后3 d加Nif或Men 5 mg·kg^-1·d^-1, ig，并在缺血过程中加入Nif或Men 0.5 μmol·L^-1可防止缺血再灌后左室收缩压，左室压最大变化速率及心率的降低，增加冠脉流量，减轻LVEDP的上抬，使心功能曲线和压力-容积曲线接近 正常. 缺血再灌和Met撤药后缺血再灌使心肌β受体密度增加，Nif或Men可使之维持正常. 本研究提示，Nif和Men对Met撤药后缺血再灌心肌功能的保护作用与其维持细胞膜β受体数目的稳定有关.

Effects of nifedipine and menidipine on cardiac function and β-adrenoceptor density in ischemic-reperfused rat hearts after metoprolol withdrawal

The effects of nifedipine (Nif) and menidipine (Men) on cardiac function and myocardium β-adrenoceptor density in isolated ischemic-reperfused rat hearts after metoprolol (Met) withdrawal were investigated. Ischemia (60 min) and reperfusion (20 min) reduced left ventricular systolic function, held down the starling curve; lifted left ventricular end diastolic pressure (LVEDP) and the pressure-volume (P-V) relationship curve. Met (50 mg·kg^-１·d^-１, ig, 2 weeks, withdrawal 1 d) slightly improved cardiac function. Met (administrated as above) plus Nif or Men (5 mg·kg^-１·d^-１, ig, from 3 d before experiment, 0.5 μmol·L^-１ for ischemia perfusion) significantly improved left ventricular systolic pressure, ±dp/dt_max, heart rate and coronary flow, decreased the abnormal rise of LVEDP, made both the starling and P-V curves closing to the control. Myocardium β-adrenoceptor density was increased after either Met withdrawal or/and ischemia-reperfusion, Nif or Men kept the number of β-adrenoceptor being normal. These results suggest that the protective effects of Nif and Men on ischemia reperfusion myocardium after Met withdrawal be related to their effects on the β-adrenoceptor number stabilizing.