PLASMA ADENOSINE AND CARDIOVASCULAR-RESPONSES TO DIPYRIDAMOLE IN FETAL SHEEP

The effects of dipyridamole infusion on fetal arterial plasma adenosin e level, [ADO], and the systemic cardiovascular system were studied in 10 fetal sheep at 130-135 days gestational age. Dipyridamole (0.25 mg /kg) was infused into the fetuses intravenously during normoxia and hy poxia. Plasma [ADO] was measured using high-performance liquid chromat ography, (HPLC), and fetal heart rate and arterial blood pressure were monitored throughout the study. These studies were performed in the a bsence and presence of theophylline, an adenosine receptor antagonist. During normoxia (PO2, 23.8 +/- 2.0 Torr), dipyridamole infusion incre ased fetal plasma [ADO] from 0.82 +/- 0.10 muM to 1.41 +/- 0.16 muM wi thin 1 min (P<0.01) and fetal heart rate from 157 +/- 6 bpm to 174 +/- 7 bpm (P<0.01), but did not change mean blood pressure. Fetal plasma [ADO] and fetal heart rate returned to basal levels quickly. Treatment with theophylline did not alter the elevation of plasma [ADO] after d ipyridamole infusion, but abolished responses of fetal heart rate to d ipyridamole infusion. After 15 min of hypoxia with an average arterial PO2 of 15.4 +/- 1.1 Torr, fetal plasma [ADO] increased to 1.15 +/- 0. 14 muM (P<0.01). Dipyridamole infusion then further raised fetal plasm a [ADO] to 1.67 +/- 0.27 muM (P<0.01). The duration of the increase of fetal plasma [ADO] after dipyridamole infusion was no longer in hypox ia than in normoxia, however there was no significant change in the pa ttern of transient fetal bradycardia and persistent hypertension. Thes e results suggest that dipyridamole exerts its effects on the systemic cardiovascular system, at least partially, by elevating plasma [ADO] during normoxia. However, elevation of plasma [ADO] by dipyridamole do es not correlate well with the responses of heart rate and blood press ure to hypoxia in fetal sheep.