Vasoconstrictor response to prostacyclin in rabbit pulmonary circulation.
We have determined the effect of prostacyclin (PGI2) on segmental vascular resistance in rabbit lungs. Lungs of 26 rabbits were isolated and perfused with blood; 16 adult, greater than 6 months old, five juvenile, 6-8 week old and five neonatal, 2-3-week old. Six of the adult lungs were pretreated with indomethacin to block cyclooxygenase, prior to infusion of PGI2. In all lungs, flow was adjusted initially to keep pulmonary artery pressure approximately 20 cmH2O, left atrial and airway pressures being 8 and 6 cmH2O, respectively (zone 3), and then kept constant. We measured pulmonary artery pressure continuously and in the 10 untreated adult lungs, in which a vasoconstrictor response to PGI2 was obtained, we also measured pressures in 20-50 microns diameter subpleural arterioles and venules by the micropipette-servonulling method. We found that in juvenile and neonatal rabbit lungs, PGI2 did not change total vascular resistance significantly but in untreated adult lungs, it caused a significant increase in total vascular resistance only after a dose of 10 micrograms/kg. This age-related difference in vasoconstrictor response to PGI2 was not related to baseline total vascular resistance in the three groups of lungs. In adult lungs, vasoconstriction occurred mainly in arteries with a small effect in veins. Circulating levels of thromboxane B2, leukotriene C4, and 6-keto-PGF1 alpha increased following PGI2 infusion in adult lungs, whereas in neonatal lungs, only 6-keto-PGF1 alpha increased significantly. Indomethacin pretreatment completely abolished the vasoconstrictor response to PGI2. We conclude that PGI2-induced vasoconstriction is age and dose dependent in isolated rabbit lungs and that a cyclooxygenase product, such as thromboxane A2, may play a role in mediating the vasoconstriction.
Kaapa
P
P
Department of Pediatrics, UCLA School of Medicine, Torrance 90509.
Raj
J U
JU
Ibe
B O
BO
Anderson
J
J
D000375:Aging; D000818:Animals; D015777:Eicosanoids / Q000097:blood; D011464:Epoprostenol / Q000494:pharmacology*; D066298:In Vitro Techniques; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D015777:Eicosanoids; D014662:Vasoconstrictor Agents; D011464:Epoprostenol