ADENOSINE MODULATES HYPOXIA-INDUCED ATRIAL-NATRIURETIC-PEPTIDE RELEASE IN FETAL SHEEP

The effects of adenosine on atrial natriuretic peptide (ANP) secretion were determined in chronically catheterized fetal sheep (> 0.8 term). Adenosine was infused into the the right jugular vein for 1 h at 8 +/- 0.4 (5 fetuses), 160 +/- 8 (6 fetuses), and 344 +/- 18 mu g . min(-1). kg estimated fetal wt(-1). Fetal arterial blood gases and pH were generally unaffected by adenosine, although mean arterial CO2 tension increased transiently by 2-5 Torr and pH fell progressively during the highest rate of infusion. During the intermediate and high infusion rates, fetal hemoglobin concentrations increased by 11-13% and mean fetal heart rate rose by 18% from a control value of similar to 167 beats/min. Mean arterial pressure was not affected during adenosine infusion. Adenosine significantly increased fetal plasma ANP levels, with maximum concentrations 1.80, 2.36, and 2.51 times greater than control means (142-166 pg/ml) for the respective infusion rates of 8, 160, and 344 mu g . min(-1). kg estimated fetal wt(-1). In seven fetuses, reducing fetal arterial O-2 tension by similar to 9-10 Torr from a control of 23 +/- 1.3 Torr increased plasma ANP concentrations similar to 2.4 times the control mean of 176 pg/min. Adenosine-receptor blockade with 8-(p-sulfophenyl)-theophylline reduced by 50% the maximum hypoxia-induced rise in plasma ANP concentrations. It is concluded that adenosine causes a dose-dependent rise in fetal plasma ANP concentrations and modulates fetal ANP release during hypoxia.