An antiadrenergic effect of adenosine on guinea-pig but not rabbit ventricles.

The antiadrenergic effect of adenosine was investigated using isolated guinea-pig heart and guinea-pig and rabbit papillary muscle. Adenosine, 15 microM, completely abolished the increased tension stimulated by 0.1-1.0 nM isoprenaline in Langendorff-perfused guinea-pig hearts. With guinea-pig papillary muscles, adenosine decreased by 40% the increased force stimulated by 1-10 nM isoprenaline. When 5 microM 2-chloroadenosine was used in conjunction with 1 unit ml-1 adenosine deaminase, a complete inhibition of the isoprenaline-stimulated tension was seen in guinea-pig papillary muscles. The antiadrenergic effect of 2-chloroadenosine was blocked by 8-phenyltheophylline. In rabbit, there was little effect of 2-chloroadenosine (plus deaminase) on isoprenaline-stimulated tension. (-)-N6 (R-phenylisopropyl)-adenosine (PIA) had no effect on basal or isoprenaline-stimulated adenylate cyclase activity of guinea-pig or rabbit sarcolemmal membranes. We conclude that the antiadrenergic effect of adenosine is mediated by A type receptors and is seen in guinea-pig but not rabbit. Production of adenosine by superfused papillary muscle may obscure the effect of added adenosine. We find no evidence that the antiadrenergic effect is mediated by inhibition of adenylate cyclase.