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

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. Skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in the finger nailfold. The adenosine uptake inhibitor Dip (approximately 1-3 microM in plasma) increased plasma adenosine from 0.15 +/- 0.03 to 0.29 +/- 0.03 microM (p less than 0.01) and heart rate (HR) by 13 +/- 2 beats/min (p less than 0.01) and reduced diastolic blood pressure by 6 +/- 2 mmHg (p less than 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 microM 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. Our results support the hypotheses that Dip dilates blood vessels in man by elevating endogenous adenosine and that theophylline acts as an adenosine antagonist. Under basal conditions, the skin microcirculation appears to be regulated mainly by factors other than adenosine.

Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine.

“…Although plasma concentrations were not measured in this study, previous clinical studies in which administered doses of dipyridamole were similar to those used in the present study demonstrate an approximate doubling of venous plasma concentrations of adenosine, from 0.15 (control) to 0.29 ,uM after intravenous dipyridamole. 19 Similarly, oral dipyridamole has been shown to increase plasma adenosine levels. 24 Dipyridamole is not known to have direct electrophysiologic effects on supraventricular tissues; its effects on AV nodal conduction can be entirely explained through potentiation of endogenous adenosine.15"7 Additional evidence from this study that dipyridamole's effects are mediated through enhanced adenosine levels is that aminophylline, a competitive antagonist of adenosine, reversed dipyridamole's negative dromotropic effects on AV nodal conduction.…”

Adenosine Concentration in Umbilical Cord Blood of Newborn Infants after Vaginal Delivery and Cesarean Section

“…An arterial blood sample was also taken for analyses of pH and Pco2, hypoxanthine, and plasma catecholamines. Adenosine was analyzed with HPLC, using UV detection as described elsewhere (9,14). The detection limit of adenosine and hypoxanthine in plasma samples was 30 and 100 nM, respectively.…”

“…DISCUSSION Higher levels of adenosine and hypoxanthine were found in infants born after normal vaginal delivery than in infants delivered by elective cesarean section. The latter had plasma adenosine concentrations in a similar range as resting adults (14). It is difficult to determine local production of adenosine from increased plasma concentration due to the extremely short halflife of adenosine in blood or plasma (<I0 s) (5, 7).…”

Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter

“…The clear increase in circulating adenosine and inosine levels in ENT1-deficient mice indicates that the bulk of extracellular adenosine is derived from breakdown of released adenine nucleotides. An increase of plasma adenosine levels has previously been observed in ENT1 Ϫ/Ϫ mice (28) as well as (18,33). The important question of whether an increase of extracellular adenosine through nucleotide metabolism also occurs in the JGA interstitium cannot be answered directly.…”