Developmental changes in vascular responses to histamine in normoxic and hypoxic lamb lungs

Abstract

This study of newborn (3-10 day old) and juvenile (6-8 mo old) in situ isolated lamb lungs was undertaken to determine whether 1) histamine receptor blockade accentuates hypoxic pulmonary vasoconstriction more in newborns than in juveniles, 2) histamine infusion causes a decrease in both normoxic pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in newborns, and 3) the H1-mediated dilator response to infused histamine in newborns is due to enhanced dilator prostaglandin release. Pulmonary arterial pressure (Ppa) was determined at baseline and in response to histamine (infusion rates of 0.1-10.0 micrograms.kg-1 min-1) in control, H1-blocked, H2-blocked, combined H1- and H2-blocked, and cyclooxygenase-inhibited H2-blocked lungs under "normoxic" (inspired O2 fraction 0.28) and hypoxic (inspired O2 fraction 0.04) conditions. In newborns, H1-receptor blockade markedly accentuated baseline hypoxic Ppa, and H2-receptor blockade caused an increase in baseline normoxic Ppa. In juveniles, neither H1 nor H2 blockade altered baseline normoxic or hypoxic Ppa. Histamine infusion caused both H1- and H2-mediated decreases in Ppa in normoxic and hypoxic newborn lungs. In juvenile lungs, histamine infusion also caused H2-mediated decreases in Ppa during both normoxia and hypoxia. During normoxia, histamine infusion caused an H1-mediated increase in normoxic Ppa in juveniles as previously seen in mature animals; however, during hypoxia there was an H1-mediated decrease in Ppa at low doses of histamine followed by an increase in Ppa. Combined histamine-receptor blockade markedly reduced both dilator and pressor responses to histamine infusion. Indomethacin failed to alter the H1-mediated dilator response to histamine in newborns.(ABSTRACT TRUNCATED AT 250 WORDS)