title: Cardiac chronotropic mechanisms of dimethyl sulphoxide: inhibition of acetylcholinesterase and antagonism of negative chronotropy by atropine.
abstract: The chronotropic effects of dimethyl sulphoxide (DMSO) were studied in spontaneously beating rabbit atria. Low concentrations of DMSO (0.14, 0.42 M) produced slight positive chronotropic (+C) responses; 0.84 and 1.41 M DMSO caused significant negative chronotropic (--C) responses. All concentrations decreased contractile strength. Atropine sulphate (10)-7) to 10(-5) M) antagonized the chronotropic effects, but not the inotropic effects. In the presence of atropine all DMSO concentrations produced significant +C responses. Reserpine pretreatment or propranolol did not affect contractile responses to DMSO in the absence or presence of atropine. DMSO produced concentration-dependent inhibition of acetylcholinesterase (AChE) activity of atrial homogenates. The results indicate that the --C responses are due specifically to AChE inhibition by DMSO and resulting cholinergic influences on the atrial pacemaker. Adrenergic mechanisms do not appear to mediate the +C responses. Data presented here provide evidence that a cardioactive effect of DMSO is mediated by a well-defined receptor-linked mechanism, and that this effect can be modified by a specific receptor blocking agent.
mesh_terms: D000818:Animals; D001285:Atropine / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D001285:Atropine; D012110:Reserpine; D011433:Propranolol; D004121:Dimethyl Sulfoxide