Chronic caffeine treatment causes changes in cardiac adenosine receptor function in rats

Caffeine exerts a number of cardiovascular effects via antagonism of adenosine A1 and A2a receptors, and chronic caffeine intake has been suggested to be a preventable risk factor for cardiovascular disease. We attempted, therefore, to determine the effects of chronic caffeine treatment on adenosine receptor function and the heart rate and blood pressure of anaesthetized rats. Rats were given two weeks of drinking water containing either caffeine (0.2%) or tap water alone. Rats were then anaesthetized and blood pressure and heart rate was assessed, as well as cardiovascular responses to adenosine receptor agonists and antagonists. Following 2 weeks caffeine treatment, both the resting blood pressure and heart rate of the treated rats were significantly increased compared to the non-caffeine treated (147 +/- 5 compared to 161 +/- 3 mm Hg). Negative chronotropic responses to A1 receptor agonist N6 cyclopentyladenosine occurred at lower concentrations in caffeine-treated rats than control (2.5-fold decrease in the ED50 of bradycardic responses to N6 cyclopentyladenosine), whilst vasodilator and reflex tachycardic responses to A2a receptor agonist CGS 21680 were unchanged. A shorter duration of caffeine- treatment resulted in moderate increases in heart rate and bradycardic responses to N6 cyclopentyladenosine. In summary, we found changes in resting heart rate and blood pressure in caffeine-treated rats which were concurrent with changes in adenosine receptor function.