title: Sustained fetal pulmonary vasodilation with prolonged atrial natriuretic factor and GMP infusions.
abstract: 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 micrograms/min), 8-BrcGMP (50 micrograms/min), prostaglandin D2 (PGD2, 0.4 micrograms/min), or acetylcholine (ACh, 1.5 micrograms/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.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
authors.forename: S H
authors.initials: SH
authors.lastname: Abman
authors.forename: F J
authors.initials: FJ
authors.lastname: Accurso
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007261:Infusions, Intra-Arterial; D008168:Lung / Q000098:blood supply* / Q000196:embryology / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep / Q000502:physiology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D000109:Acetylcholine; D015230:Prostaglandin D2; D010100:Oxygen