Theophylline antagonizes cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine

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Abstract
Effects of the vasodilator dipyridamole (Dip) on plasma adenosine levels, heart rate, blood pressure and skin microcirculation were studied in 13 healthy male volunteers. Venous plasma concentrations of adenosine, catecholamines, dipyridamole and theophylline were determined by HPLC [high performance liquid chromatography]. Skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in the finger nailfold. The adenosine uptake inhibitor Dip (.apprx. 1-3 mM in plasma) increased plasma adenosine from 0.15 .+-. 0.03 to 0.29 .+-. 0.03 .mu.M (P < 0.01) and heart rate (HR) by 13 .+-. 2 beats/min (P < 0.01) and reduced diastolic blood pressure by 6 .+-. 2 mmHg (P < 0.05). Dip did not significantly affect the skin circulation since basal CBV, digital pulse amplitude (DAPA), skin temperature and post-occlusive reactive hyperemia were unchanged. Plasma catecholamine levels were also unaffected. The adenosine receptor antagonist theophylline (45-55 .mu.M in plasma) did not influence basal plasma catecholamine or adenosine levels, HR, blood pressure or skin microcirculation. Following theophylline, Dip caused similar elevations of plasma adenosine but no changes in HR or blood pressures. Dip apparently dilates blood vessels in man by elevating endogenous adenosine and theophylline acts as an adenosine antagonist. Under basal conditions, the skin microcirculation appears to be regulated mainly by factors other than adenosine.