Dynamic cerebral and systemic circulatory effects of adenosine, theophylline and dipyridamole

The effects of intravenous adenosine, dipyridamole and theophylline on local cerebral blood flow were studied in conscious rabbits. Long-term quantitative blood flow measurements were performed in 5 cerebral structures together with tissue pO2 and pCO2 measurements by a mass spectrometry technique. In an additional study, the time course of the cerebrovascular changes was determined by thermal clearance. It was found that: firstly, adenosine failed to modify local blood flow except in the caudate nucleus; secondly, dipyridamole increased cerebral blood flow in all 5 structures under study, and lastly, theophylline decreased cerebral blood flow in the same 5 structures. The increase in caudate blood flow induced by adenosine was instantaneous and lasted only for the duration of the infusion, whereas the cerebrovascular changes induced by dipyridamole and theophylline were gradual and persisted after their administration. Theophylline blocked the systemic and cerebrovascular changes caused by adenosine alone and by dipyridamole alone. In anesthetized rabbits, the intracarotid infusion of adenosine showed that the caudate reaction only occurred in the ipsilateral hemisphere. Taken together, our findings suggest that the transport system for adenosine in cerebral vessels is not only species-dependent but also structure-dependent. Furthermore, perivascular adenosine helps to maintain resting cerebrovascular tone and finally, cerebral adenosine may be involved in the control of cerebral blood flow via specific adenosine receptors.