Developmental changes in effects of histamine on segmental pulmonary vascular resistances.
In mature animals histamine infusion typically causes an H1-mediated increase and H2-mediated decrease in pulmonary vascular resistance (PVR). Moreover, low histamine concentrations can cause H1-mediated relaxation of vascular strips in mature animals, and in newborn animals histamine infusion causes only H1-mediated decreases in PVR. The mechanisms responsible for the different H1-mediated responses are unknown. We used an inflow-outflow occlusion technique to identify the sites of H1- and H2-mediated responses in lungs of developing lambs. Histamine was infused at 1.0 and 10.0 micrograms.kg-1.min-1 in control and H1- and H2-blocked lungs of newborn and juvenile lambs under "normoxic" and hypoxic conditions and in hypoxic H2-blocked lungs of mature sheep. In newborns histamine caused significant H1-mediated decreases in resistance across the arterial (delta Pa) and middle (delta Pm) segments of the circuit during both normoxia and hypoxia. In normoxic juveniles low-dose histamine caused H1-mediated decreases in the resistance across delta Pa and delta Pm, but the resistances across delta Pm rose above baseline at the higher dose. The venous segment exhibited only a high-dose increase in resistance. During hypoxia, the high-dose H1-mediated pressor response of delta Pm was attenuated compared with that during normoxia; however, the increase in venous resistance was unaffected. In hypoxic mature sheep, no low dose H1-mediated decrease in segmental resistances was seen, but at the higher dose an increase in all resistances occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, Montreal Children's Hospital, Quebec, Canada.
J B
JB
Gordon
S
S
Clément de Cléty
K
K
Chu
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000502:physiology; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine