Adenosine receptors mediating cardiac depression

Several adenosine analogs were evaluated for their effects on rate and contractility in guinea pig isolated atria. Among adenosine agonists, (-)-N-(1-methyl-2-phenylethyl) adenosine (l-phenylisopropyladenosine; l-PIA) and N-cyclohexyladenosine (CHA), decreased rate and force at nanomolar concentrations, whereas 2-chloroadenosine, N,N-dimethyladenosine (N6-dimethyladenosine) and (+)-N-(1-methyl-2-phenylethyl)adenosine (d-phenylisopropyladenosine; d-PIA) were less potent cardiac depressants. The degree and order of potency of these agonists suggest that the cardiac depressant effects of adenosine are mediated via A1-receptors. The cardiac depressant effects of CHA and l-PIA were antagonized by theophylline and 1,3-diethyl-8-phenylxanthine (DPX).