Waite R P, Pang C C, Walker M J
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
J Pharm Pharmacol. 1990 May;42(5):325-31. doi: 10.1111/j.2042-7158.1990.tb05420.x.
Representative calcium antagonists from proposed class I (nifedipine), class II (verapamil) and class III (flunarizine) have been examined for effects on blood pressure, heart rate, ventricular pressures, ECG, cardiac output and regional blood flow in pentobarbitone-anaesthetized rats. Flow was measured by the microsphere technique. Low and high infusion rates of each drug were chosen to decrease mean arterial pressure by 25 and 40 mmHg, respectively. At equi-depressor infusion rates, all drugs equally decreased total peripheral resistance and slightly increased cardiac output and stroke volume. Heart rate was decreased by verapamil and flunarizine, but increased by nifedipine. Verapamil markedly decreased dP/dtmax of ventricular pressure and prolonged the PR-interval. Flunarizine was similar. Nifedipine decreased dP/dtmax and had no effect on the PR-interval of the ECG. Similar effects on regional blood flow were seen with the three drugs; flow to lungs, heart, liver, skeletal muscle and stomach increased. Correction for blood pressure changes, i.e. conductance, showed that vasodilatation occurred in all regions, with all drugs, except for the skin. Therefore, representatives from three sub-classes of calcium antagonists had similar effects on blood flow but different effects on the heart.
已对拟分类为I类（硝苯地平）、II类（维拉帕米）和III类（氟桂利嗪）的代表性钙拮抗剂进行了研究，观察其对戊巴比妥麻醉大鼠的血压、心率、心室压力、心电图、心输出量和局部血流的影响。血流通过微球技术测量。选择每种药物的低输注速率和高输注速率，以使平均动脉压分别降低25 mmHg和40 mmHg。在等降压输注速率下，所有药物均同等程度地降低总外周阻力，并略微增加心输出量和每搏输出量。维拉帕米和氟桂利嗪使心率降低，但硝苯地平使心率增加。维拉帕米显著降低心室压力的dP/dtmax，并延长PR间期。氟桂利嗪情况类似。硝苯地平降低dP/dtmax，对心电图的PR间期无影响。三种药物对局部血流的影响相似；肺、心脏、肝脏、骨骼肌和胃的血流增加。校正血压变化（即传导率）后发现，除皮肤外，所有药物在所有区域均引起血管舒张。因此，钙拮抗剂三个亚类的代表性药物对血流的影响相似，但对心脏的影响不同。
