Adenosine is a key physiological modulator of cardiovascular function with potential pharmacological applications in controlled hypotension and regional vasodilation.
The results, briefly summarized above, indicate that adenosine could be a physiologically important modulator of several aspects of cardiovascular regulation. Most cells are equipped with adenosine receptors. These receptors are of at least two subtypes which can be defined by the relative agonist potency. At these adenosine receptors, methylxanthines, including caffeine and theophylline, act as competitive antagonists. The role of adenosine antagonism, as a mechanism behind the cardiovascular effects of these xanthines, was recently reviewed (Fredholm, 1984). The concentrations of adenosine are low during resting conditions, but may be raised substantially by, for example, hypoxia, ischaemia and increased mechanical or biochemical work. The adenosine levels can also be raised by drugs, including uptake inhibitors such as dipyridamole. Already the concentrations of adenosine that occur during basal conditions are sufficient to produce significant effects, for example, on blood-flow. When the concentrations are raised the importance of endogenous adenosine becomes even greater. Adenosine may not only be of physiological significance but may also be pharmacologically important. First, there are several drugs that may act by affecting the levels of adenosine or by influencing its receptors. Second, the possibility exists that adenosine itself could be used clinically. For example, adenosine may be an attractive alternative to sodium nitroprusside or nitroglycerin when controlled hypotension is to be achieved. Adenosine may also be used to preserve blood platelets during extracorporal circulation or to produce selective regional vasodilatation. Both the physiological and pharmacological aspects are subject to intense study in several laboratories.
Fredholm et al. (Sat,) studied this question.