SUSTAINED FETAL PULMONARY VASODILATION WITH PROLONGED ATRIAL-NATRIURETIC-FACTOR AND GMP INFUSIONS

To study mechanisms of vasodilation and factors that maintain high pulmonary vascular resistance in utero, we measured changes in blood flow and the pressure-flow relationship of the pulmonary circulation during prolonged exposures to direct-acting guanosine 3',5'-cyclic monophosphate (cGMP) vasodilators, atrial natriuretic factor (ANF), and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and compared hemodynamic responses with other vasodilator stimuli in chronically prepared fetal lambs. The fetus was treated with 2 h of intrapulmonary infusions of ANF (0.15-mu-g/min), 8-BrcGMP (50-mu-g/min), prostaglandin D2 (PGD2, 0.4-mu-g/min), or acetylcholine (ACh, 1.5-mu-g/min) or increases in fetal PO2. Despite continued exposure to increased PO2, PGD2, and ACh, elevations of pulmonary blood flow and slopes of the pressure-flow relationship were not sustained, with both significantly decreased at 2 h from peak values. In contrast, pulmonary blood flow and pressure-flow slopes remained increased throughout 2 h of exposures to ANF and 8-BrcGMP. Adenosine 3',5'-cyclic monophosphate caused less change in blood flow than 8-BrcGMP within the dose range studied. We conclude that unlike other stimuli, direct-acting cGMP vasodilators are able to sustain vascular relaxation of the fetal pulmonary circulation.