Cardiac chronotropic mechanisms of dimethyl sulphoxide: inhibition of acetylcholinesterase and antagonism of negative chronotropy by atropine.
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.
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
D002800:Cholinesterase Inhibitors; D001285:Atropine; D012110:Reserpine; D011433:Propranolol; D004121:Dimethyl Sulfoxide