title: Anisodamine inhibits cardiac contraction and intracellular Ca(2+) transients in isolated adult rat ventricular myocytes.
abstract: 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 Ca(2+) properties were evaluated using an IonOptix Myocam system. Contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca(2+) 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/TR(90) and tau. Pretreatment with the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) 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.
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND 58203, USA.
authors.forename: Faye L
authors.initials: FL
authors.lastname: Norby
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012991:Solanaceous Alkaloids / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D012991:Solanaceous Alkaloids; C003922:anisodamine; D002217:Carbachol; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester