Effect of i.v. dipyridamole on cerebral blood flow, blood pressure, plasma adenosine and cAMP levels in rabbits

In response to intravenous administration of dipyridamole, the quantitative and temporal changes in plasma adenosine and cyclic AMP (cAMP) levels in relation to the changes in cerebral blood flow (CBF) and mean arterial blood pressure (MABP) have not been studied. Therefore, we investigated simultaneously the changes in CBF (hydrogen and thermal clearance methods), MABP, plasma adenosine (HPLC) and cAMP (radioimmunoassay) levels for 1 h after intravenous injection of 0.7 and 1.4 mg/kg dipyridamole in rabbits. In separate experiments, only plasma adenosine concentrations were measured to determine how and for how long intravenous administration of 0.7 mg/kg dipyridamole is able to inhibit the removal of plasma adenosine. Dipyridamole decreased MABP, increased plasma adenosine and cAMP levels in a dose-dependent manner. The dose-dependency of increases in CBF could not be demonstrated owing to the marked hypotension. The increase in plasma adenosine concentrations was biphasic. The first peak could be detected at the end of the dipyridamole injection. The second peak occurred 20 min after drug administration, simultaneously with the maximal increases in plasma cAMP level and CBF, whereas the maximal fall in MABP developed earlier. Intravenous administration of 0.7 mg/kg dipyridamole inhibited adenosine uptake only by 25%, which lasted less than 10 min. We concluded that intravenously given dipyridamole is responsible only for the initial short-lasting elevation of plasma adenosine concentration, and is able to induce vasodilation without either dipyridamole itself or adenosine necessarily gaining access to the muscular layer.