Anisodamine inhibits cardiac contraction and intracellular Ca2+ transients in isolated adult rat ventricular myocytes

Increased cardiac workload often leads to serious complications during cardiac surgery such as pericardiopulmonary bypass. Various agents have been applied to lower peripheral resistance and cardiac workload, one of which, anisodamine, is widely used in Asia. However, the direct action of anisodamine on cardiac contractile property is essentially unknown. This study was designed to examine the influence of anisodamine on ventricular contractile function at the single cardiac myocyte level. Ventricular myocytes from adult rat hearts were stimulated to contract at 0.5 Hz, and mechanical and intracellular Ca2+ properties were evaluated using an IonOptix Myocam system. Contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca2+ fluorescence intensity change (DeltaFFI) and decay (tau). Anisodamine exhibited a concentration-dependent (10(-12)-10(-6) M) inhibition in PS and DeltaFFI, with maximal inhibitions of 44.7% and 47.2%, respectively. Anisodamine inhibited +/-dL/dt, lowered resting FFI but elicited no effect on TPS/TR90 and tau. Pretreatment with the nitric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 100 muM) abolished the inhibitory effect of anisodamine in cell shortening. In addition, anisodamine prevented cholinoceptor agonist carbachol-induced positive cardiac contractile response. This study demonstrated a direct cardiac depressive action of anisodamine at the myocyte level, which may be related to, at least in part, NO production and cholinoceptor antagonism. (C) 2002 Elsevier Science B.V. All rights reserved.