Ovine fetal coronary and cerebral vascular responses to forskolin

The time related hemodynamic responses to forskolin-elicited increases in cAMP were studied in the near-term fetus. Catheters and electrodes were inserted into 6 fetal sheep to measure arterial, venous and thoracic pressures, electrocorticogram, and electrocardiogram. At gestational day 134, experiments were performed to determine the effect of forskolin infusion (400 micrograms/ml at 1.03 ml/min for 5 min) on fetal blood pressure, coronary and cerebral blood flow and resistance. Blood flow measurements were made using 15 microns microspheres labelled with radioactive isotopes during the control period and at 0, 5, 10, 15, and 45 min after forskolin infusion. Forskolin infusion was always initiated during a high-voltage electrocortical epoch and was given twice in each animal. In each case, forskolin caused electrocortical activity to change from high-voltage state to an intermediate voltage state. Blood pressure fell significantly by the end of the infusion period and returned to control levels 10 min later. Fetal heart rate and coronary blood flow were immediately elevated by forskolin (P less than 0.01) whereas cerebral blood flow did not increase until 5 min later (P less than 0.01). Cerebral blood flow was still elevated (P less than 0.05) 45 min after the end of forskolin infusion, whereas coronary blood flow had returned to control levels. Both cerebral and coronary vascular resistance fell significantly in response to forskolin infusion (P less than 0.01). This effect lasted at least 15 min and had returned to control levels 45 min after forskolin had been terminated.