EXOGENOUS INFUSION OF ADENOSINE DEPRESSES WHOLE-BODY O-2 USE IN FETALNEONATAL SHEEP/

To examine a possible metabolic regulatory role for adenosine, infusio ns of adenosine and adenosine deaminase were given to 11 near-term fet al sheep during the simulation of birth in utero. Fetal arterial blood gases, the concentration of a number of metabolites, insulin, and who le body O-2 consumption (Vo(2)) were measured. After intrauterine vent ilation and cord occlusion, fetal/neonatal Vo(2), measured by closed-c ircuit respirometry, averaged 11.0 +/- 1.1 (SE) ml (STPD). min(-1). kg fetal wt(-1) and plasma adenosine concentration ([Ado]) was 1.29 +/- 0.21 mu M. Infusion of adenosine (1.5 mu mol . min(-1). kg(-1)) during the next 30-min interval increased [Ado] to 1.57 +/- 0.28 mu M (not s ignificant) and decreased Vo(2) to 7.7 +/- 0.5 ml . min(-1). kg(-1) (P < 0.05). The infusion reduced systolic blood pressure by 19% (P < 0.0 1) and diastolic blood pressure by 25% (P < 0.01) and increased heart rate by 19% (P ( 0.01). At the highest rate of adenosine infusion stud ied (6 mu mol . min(-1). kg(-1)), [Ado] increased to 4.27 +/- 0.46 mu M (P < 0.001) and Vo(2) did not measurably decline further, although t here were further decreases in blood pressure and increases in heart r ate. After administration of adenosine deaminase, [Ado] decreased to 0 .58 +/- 0.13 mu M (P < 0.05), whereas Vo(2) increased to 11.2 +/- 0.8 ml . min(-1). kg(-1) (P < 0.05); blood pressure and heart rate returne d to basal levels. The dependence of Vo(2) on [Ado] is described by th e relationship Vo(2) = 6.14 + 4.89 exp(-0.45[Ado]) (n = 144; r = 0.34; P < 0.001). Throughout the experiment, arterial O-2 content and plasm a glucose, lactate, glycerol, and fatty acid concentrations were norma l or elevated, and, therefore, O-2 lack and substrate deficiency were unlikely to have caused the reduction in Vo(2). We conclude that plasm a adenosine may act as a messenger of energy status for the ovine fetu s/neonate and may contribute thereby to a maintenance of a balance bet ween O-2 supply and O-2 demand.