The Effect And Its Mechanism Of Anisodamine On Contractile Function And Calcium Transient In Isolated Adult Rat Ventricular Myocytes

Anisodamine was widely used as a vasoactive drug in China to improve microcirculation, especially during septic shock. Recent years it was also used to protect cardiopulmonary bypass surgery-induced hypertension. With the increased use of anisodamine in cardiovascular diseases recent researches found that anisodamine had protective effect on myocardium after burn and myocardial ischemic reperfusion injury. Its mechanism has been demonstrated to be associated with its ability of antilipid peroxidation and membrane stabilization. It has been reported that M₁-M₅ subtype muscarinic receptor located in myocytes. M₁ and M₃ subtype muscarinic receptor coupled with G_q/11 protein and can affect theactivity of PLC and the concentration of IP3. IP3 can affect the calcium releasing from endoplasmic reticulum. M₂ subtype muscarinic coupled with Gi/o protein and affects the function of L-type calcium channel by AC. As we know calcium overload is a key factor of cell injury. But the direct impact on ventricular myocytes of anisodamine and its mechanism is not clear till now.Therefore, the aim of present study was to elucidate the effect of anisodamine on contractile function and calcium transient in isolated adult rat ventricular myocytes and discover its mechanism and provide theoretical evidence for the rational clinical application of anisodamine.The results are as follows:1. We observed the effect of anisodamine on resting level of calcium concentration in isolated adult rat ventricular myocytes by LSCM. The result showed that anisodamine had no significant effect on resting level of calcium concentration in isolated adult rat ventricular myocytes. There are no significant differences 3 different concentration anisodamine groups(1×10^-9, 1×10^-7, 1×10^-5mol·L^-1) and control group (P>0.05).2. We observed the effect of anisodamine on contractile function and calcium transient in isolated adult rat ventricular myocytes by edge motion detect system. The results showed that anisodamine had direct inhibitory effects on contractile function and calcium transient in isolated adult rat ventricular myocytes. After perfuse with anisodamine calcium transient (AFR) declined v.s. control group, and time to peak [Ca2+]i(TTP) and time to 50% diastolic [Ca²+] (T₅0D) increased. But the baseline of [Ca²+]i had no...