Chronic inhibition of cyclooxygenase increases role of nitric oxide in cerebrovascular responses in piglets

M. Son, S. Zuckerman

Research output: Contribution to journalArticlepeer-review

Abstract

Hypercapnia-induced cerebral vasodilation is a prostanoid associated response in the piglet, but a nitric oxide(NO) associated response in many adult models. While NO does not appear to play a major role in the maintenance of cerebral vascular tone in the newborn(NB), hypercapnia-induced cerebral vasodilation is both NO and prostanoid associated in the juvenile pig. We hypothesized that chronic inhibition of cyclooxygenase(COX) in the piglet would increase the role of the NO system in cerebrovascular responses. The closed cranial window technique was used in piglets anesthetized with α-chloralose to determine pial arteriolar response. Chronic indomethacin (75mg SR po BID) treated NB animals dilated in response to C02 similarly to control NB animals(40.8±36% vs 46.0±4.6%). Topical LNA(10 -3M) attenuates CO, induced dilation in chronic indomethacin treated animals(14.3±4.4% vs 40.8±3.6%; p<0.001). Neither indomethacin nor LNA altered response to isoproterenol. We conclude that with chronic COX inhibition, there develops a significant hypercapnia-induced cerebral vasodilation in which NO has an important role. The chronic inhibition of the NB's principal dilator system accelerates the role of the constitutive NO system in NB cerebral hemodynamics.

Original languageEnglish (US)
Pages (from-to)A247
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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