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1 Department of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, 28040 Madrid; and 2 Department of Pharmacology, School of Medicine, Universidad Autónoma, 28029 Madrid, Spain
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 MnCl2 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
-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.
piglet; superoxide; newborn
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