Mechanisms of cerebral arterial relaxations to hydrogen peroxide

Y. Iida, K. A. Jones, David Oman Warner, R. R. Lorenz, Zvonimir S Katusic

Research output: Contribution to journalArticle

Abstract

The present study was designed to determine the mechanisms of cerebral arterial relaxations to hydrogen peroxide. Rings of canine middle cerebral arteries without endothelium were suspended for isometric tension recording. Radioimmunoassay techniques were used to determine the levels of 3′,5′-adenosine cyclic monophosphate (cAMP) and 3′,5′-guanosine cyclic monophosphate (cGMP). Cytosolic calcium concentration ([Ca2+]i) was measured using the fluorescent Ca2+-sensitive dye fura 2. During contractions to uridine 5′-triphosphate (UTP), hydrogen peroxide (H2O2; 10-6 to 10-4M) caused concentration-dependent relaxations. Catalase abolished these relaxations. A cyclooxygenase inhibitor, indomethacin (10-5M) significantly reduced relaxations to low concentrations of H2O2 (10-6 to 3 × 10-5M). H2O2 produced concentration-dependent increases in levels of cAMP. Indomethacin inhibited the stimulatory effect of H2O2 on cAMP production. In contrast, H2O2 did not affect the levels of cGMP. UTP caused contractions and an increase in [Ca2+]i. Relaxations to H2O2 (10-4M) were associated with an increase rather than decrease in [Ca2+]i. These results suggest that 1) low concentrations of H2O2 may cause relaxations of cerebral arteries in part by activation of arachidonic acid metabolism via cyclooxygenase pathway with subsequent increases in cAMP levels, and 2) that high concentrations of H2O2 cause relaxations despite their ability to increase [Ca2+]i.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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Uridine Triphosphate
Uridine
Cyclic GMP
Indomethacin
Hydrogen Peroxide
hydrogen peroxide
calcium
Cerebral Arteries
Cyclooxygenase Inhibitors
Fura-2
Middle Cerebral Artery
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Metabolism
Cyclic AMP
Catalase
Endothelium
Radioimmunoassay
Canidae
guanosine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Mechanisms of cerebral arterial relaxations to hydrogen peroxide. / Iida, Y.; Jones, K. A.; Warner, David Oman; Lorenz, R. R.; Katusic, Zvonimir S.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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