FETAL CARDIOVASCULAR AND BREATHING RESPONSES TO AN ADENOSINE A(2A) RECEPTOR AGONIST IN SHEEP

CGS-21680 (CGS), a highly selective adenosine A(2a) receptor agonist, may excite the fetal carotid bodies. This study was designed to determ ine I) whether CGS stimulates fetal breathing and 2) whether sinoaorti c denervation abolishes CGS-induced tachycardia. In eight intact fetus es (>0.8 term), intra-arterial CGS infusion (6 mu g.min(-1).kg estimat ed fetal wt(-1)) increased mean arterial PCO2 by 3-7 Torr, reduced fet al arterial PO2 by 2-5 Torr, and produced a mild metabolic acidemia. H eart rate increased from 154 +/- 7 (control) to 249 +/- 12 beats/min, but mean arterial pressure was not significantly affected. CGS initial ly increased the frequency, amplitude, and incidence of fetal breathin g, but this hyperpnea was followed by prolonged respiratory depression that was not reversed with blockade of adenosine A(1) receptors. Dene rvation of both carotid bodies together with interruption of the vagi abolished the hyperpnea without altering the respiratory depression or the maximum rise in heart rate. We conclude that CGS induces i) tachy cardia by a mechanism independent of the peripheral arterial chemorece ptors, 2) hyperpnea by stimulating peripheral adenosine A(2a) receptor s, and 3) respiratory depression by activating central A(2a) receptors .