Fetal cardiovascular and breathing responses to an adenosine A2a 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 determine I) whether CGS stimulates fetal breathing and 2) whether sinoaortic denervation abolishes CGS-induced tachycardia. In eight intact fetuses (>0.8 term), intra-arterial CGS infusion (6 mu g.min(-1).kg estimated fetal wt(-1)) increased mean arterial PCO2 by 3-7 Torr, reduced fetal arterial PO2 by 2-5 Torr, and produced a mild metabolic acidemia. Heart rate increased from 154 +/- 7 (control) to 249 +/- 12 beats/min, but mean arterial pressure was not significantly affected. CGS initially increased the frequency, amplitude, and incidence of fetal breathing, but this hyperpnea was followed by prolonged respiratory depression that was not reversed with blockade of adenosine A(1) receptors. Denervation 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) tachycardia by a mechanism independent of the peripheral arterial chemoreceptors, 2) hyperpnea by stimulating peripheral adenosine A(2a) receptors, and 3) respiratory depression by activating central A(2a) receptors.