萘甲异喹对离体豚鼠心肌的作用

萘甲异喹(NI)呈浓度依赖性地降低离体豚鼠心房收缩力和频率。其拮抗豚鼠左房肌Iso正性肌力作用的PD2₂′值为5.4,Ver为5.8。NI10μmol/L明显降低豚鼠乳头肌收缩力;缩短快反应APD,以对APD₂₀影响最大,但不影响APA和V_max。对高K⁺去极化慢反应动作电位,NI产生浓度依赖性负性肌力作用,同时明显降低APA,V_max,缩短APD;提高细胞外液Ca²⁺浓度可使其抑制作用逆转。结果提示NI具有钙通道阻滞作用。

EFFECT OF NAPHTHYLMETHYL ISOQUINOLINE ON THE ISOLATED GUINEA PIG MYOCARDIUM

The effect of naphthylmethyl isoquinoline on amplitude of contraction and automaticity of guinea pig atria were investigated. The compound was found to markedly inhibit the force of contraction and automaticity in a concentration-dependent way. Propranolol competitively antagonized the effect of isoproterenol with pA2 of 7.5. Naphthylmethyl isoquinoline and verapamil antagonized isoproterenol, but in a noncompetitive manner with the pD2' of 5.4 and 5.8, respectively. The effect of the compound on action potential and contractile force of guinea pig papillary muscles were also studied. It was shown to produce negative inotropic effects and shorten the fast action potential duration, but the maximal upstroke (Vmzx) and amplitude of action potential were not affected. Thus, an excitation-contraction uncoupling was observed. It also depressed the amplitude. Vmax and duration of Ca2(+)-mediated slow action potential induced by high K+. Elevation of the CaCl2 concentration from 2 to 5 mmol/L reversed its inhibition partially. These results indicate that naphthylmethyl isoquinoline has a blocking effect on calcium channels.