Do inhibitors of lipoxygenase and cyclooxygenase block neonatal hypoxic pulmonary vasoconstriction?
Lipoxygenase products have been suggested as mediators of the hypoxic pulmonary pressor response in newborn animals. Data supporting this suggestion are equivocal, since lipoxygenase and leukotriene receptor antagonists that have been used may produce vasodilation because of phosphodiesterase inhibition. We used a leukotriene receptor antagonist L 649923, which appears not to have smooth muscle relaxant activity. L 649923 blocks pressor responses to leukotriene D4 (LTD4) without diminishing the pressor response to hypoxia. Also, BW 755C did not block the pressor response to hypoxia in newborn sheep and goats, whereas the pressor response to LTD4 (75 ng/kg) was depressed significantly. In newborn sheep there was an augmented response to hypoxia with BW 755C, which is consistent with cyclooxygenase inhibition. Finally, the thromboxane receptor antagonist SQ 29548 was investigated in both species. With this agent the pressor response to LTD4 in contrast to that of hypoxia was completely inhibited. We conclude that thromboxanes are involved in the pressor response to LTD4 in newborn lambs and goats. These data do not support the view that leukotrienes are involved in the ovine or caprine neonatal pulmonary pressor response to hypoxia.
Cassin
S
S
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.
Gause
G
G
Davis
T
T
ter Riet
M
M
Baker
R
R
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D010654:Phenylbutyrates / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors; D012756:Sheep / Q000502:physiology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010654:Phenylbutyrates; D011720:Pyrazoles; D013189:SRS-A; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C045749:SQ 29548; C050033:L 649923; D001091:Arachidonate Lipoxygenases