Developmental changes in synthesis of and responsiveness to prostaglandins I2 and E2 in hypoxic lamb lungs.
Previous studies have shown that the attenuated hypoxic pulmonary vasoconstriction (HPV) of young newborn lamb lungs was enhanced by cyclooxygenase inhibition. We sought to determine whether this reflected greater synthesis of and (or) responsiveness to dilator prostaglandins (PG). Protocol 1 measured responses to graded hypoxia and perfusate concentrations of 6-keto-PGF1alpha (the stable metabolite of PGI2) and PGE2 in isolated lungs from 1-day- and 1-month-old lambs. Protocol 2 compared dose responses and segmental vascular resistances during infusion of PGI2 and PGE2 in hypoxic, cyclooxygenase-inhibited, lungs from 1- to 2-day-old and 1- to 3-month-old lambs. Lungs of 1-day-old lambs with attenuated responses to 4% O2 had significantly higher perfusate concentrations of 6-keto-PGF1alpha and PGE2, but responses to both PGE2 and the more potent vasodilator, PGI2 did not differ with age. These data support the hypothesis that attenuated HPV in young newborn lamb lungs is due to increased synthesis of dilator PG, particularly PGI2.
Department of Pediatrics, The Montréal Children's Hospital and McGill University Research Institute, QC, Canada.
S C
SC
de Cléty
M K
MK
Decell
M L
ML
Tod
P
P
Sirois
J B
JB
Gordon
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015232:Dinoprostone