Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep

The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumental with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (FIO2 = 0.12) caused pulmonary artery pressure (PPA) to increase from 17.2 +/- 0.4 to 27.0 +/- 1.0 cm H2O (mean +/- SEM, P less than 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 +/- 0.33 to 4.71 +/- 0.38 cm H2O x L-1 x min (P less than 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O2, PPA rose only 21.3 +/- 1.11 cm H2O and PVR decreased to 3.51 +/- 0.31 cm H2O x L-1 x min. This was a significantly (P less than 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had to significant effect on PPA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 micrograms/kg/min) and intravenous prostaglandin H2-analog (0.74 microgram/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction.