Shlafer_1976_Arch.Int.Pharmacodyn.Ther_221_21

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.