Pulmonary vascular histamine receptors in newborn and young lambs

Histamine H1- and H2-receptor-mediated pulmonary vascular responses were evaluated in six newborn and three 4-wk-old lambs. Base-line pulmonary vascular resistance (PVR) was elevated via alveolar hypoxia. Changes in PVR were then determined over a range of 0.001-1.0 microgram/kg of histamine. Multiple phases of relaxation of PVR were observed in all lambs. Two distinct plateaus of relaxation occurred between 0.001 and 0.075 micrograms/kg of histamine. The response at the first and major plateau was abolished by the H1-receptor antagonist, diphenhydramine. The second and smaller relaxation appeared to be attenuated by the H2-receptor antagonist, metiamide. Qualitatively similar results were obtained in the older lambs. Larger doses of histamine, 0.1-1.0 microgram/kg, produced further, but variable decreases in PVR as well as changes in systemic blood pressure. Our findings in newborn lambs are in contrast to those in adults where less sensitive H1-receptors mediate pulmonary vasoconstriction.