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 (ΔFFI) and decay (τ). Anisodamine exhibited a concentration-dependent (10^-12-10^-6 M) inhibition in PS and ΔFFI, 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 τ. Pretreatment with the nitric oxide synthase (NOS) inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME, 100 μM) 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.