Influence of adenosine and lowered cerebral blood flow on the cerebrovascular effects of theophylline.

The response of brain blood vessels to theophylline infused intra-arterially was evaluated. The experiments were performed on isolated canine brains perfused by donor dogs. Thus secondary effects due to theophylline were eliminated. Arterial pO2, pCO2, pH and brain temperature were kept constant. Cerebral vascular resistance (CVR) was calculated from total venous outflow and cerebral perfusion pressure. A 2 mg dose of theophylline per brain was given at normal cerebral perfusion pressure (about 81 mm Hg), at lowered cerebral perfusion pressure (about 37 mm Hg), and during an adenosine infusion lasting 10 min (10-minus 7 mol/min). At normal perfusion pressure theophylline showed a significant 15% decrease of CVR, but at lowered perfusion pressure a significant 19% increase occurred. During infusion of adenosine, which decreased CVR by 23%, theophylline again increased CVR by 20%, thus demonstrating an adenosine-theophylline antagonism. From our results, it is suggested that adenosine could be involved in the vasodilatation of cerebral vessels in the hypoxic brain.