Postnatal maturation in nitric oxide-induced pulmonary artery relaxation involving cyclooxygenase-1 activity.
The maturation in the vasodilator response to nitric oxide (NO) in isolated intrapulmonary arteries was analyzed in newborns and 15- to 20-day-old piglets. The vasodilator responses to NO gas but not to the NO donor sodium nitroprusside increased with age. The inhibitory effects of the superoxide dismutase inhibitor diethyldithiocarbamate and xanthine oxidase plus hypoxanthine and the potentiation induced by superoxide dismutase and MnCl(2) of NO-induced vasodilatation were similar in the two age groups. Diphenyleneiodonium (NADPH oxidase inhibitor) potentiated the response to NO, and this effect was more pronounced in the older animals. The nonselective cyclooxygenase inhibitors indomethacin and meclofenamate and the preferential cyclooxygenase-1 inhibitor aspirin augmented NO-induced relaxation specifically in newborns, whereas the selective cycloxygenase-2 inhibitor NS-398 had no effect. The expressions of alpha-actin, cycloxygenase-1, and cycloxygenase-2 proteins were similar, whereas Cu,Zn-superoxide dismutase decreased with age. Therefore, the present data suggest that the maturational increase in the vasodilatation of NO in the pulmonary arteries during the first days of extrauterine life involves a cycloxygenase-dependent inhibition of neonatal NO activity.
Pérez-Vizcaíno
Francisco
F
Department of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain. fperez@ucmail.ucm.es
López-López
José G
JG
Santiago
Rocío
R
Cogolludo
Angel
A
Zaragozá-Arnáez
Francisco
F
Moreno
Laura
L
Alonso
María J
MJ
Salaices
Mercedes
M
Tamargo
Juan
J
D000818:Animals; D000831:Animals, Newborn; D002614:Chelating Agents / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000201:enzymology* / Q000254:growth & development; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D002614:Chelating Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; D004050:Ditiocarb; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase