Role of tyrosine phosphorylation in the regulation of cerebral vascular tone in newborn pig in vivo.
The role of tyrosine phosphorylation was investigated using protein tyrosine phosphatase inhibitors in newborn pigs equipped with a cranial window in vivo. We tested the hypothesis that cyclooxygenase and nitric oxide (NO) synthase are physiological targets for tyrosine phosphorylation in cerebral circulation. Phenylarsine oxide dilated pial arterioles and increased prostacyclin and prostaglandin E2 in cortical periarachnoid fluid; these responses were inhibited by indomethacin. Nomega-nitro-L-arginine methyl ester (L-NAME) and Nomega-nitro-L-arginine (L-NNA) inhibited the vasodilation to phenylarsine oxide; the effects of NO synthase inhibitors and indomethacin were additive. Cyclooxygenase-mediated vascular responses were assessed using topical application of arachidonic acid. Phenylarsine oxide and sodium orthovanadata potentiated vasodilation and prostanoid synthesis in response to arachidonic acid. Nomega-nitro-L-arginine methyl ester and Nomega-nitrol-arginine did not affect vasodilation or prostanoid production in response to arachidonic acid, indicating no cross talk between cyclooxygenase and NO synthase. These data indicate that cyclooxygenase and NO synthase are physiological targets for tyrosine phosphorylation in the cerebral circulation of newborn pigs.
Parfenova
H
H
Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee, Memphis, Tennessee 38163, USA.
Fedinec
A
A
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001152:Arsenicals / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D010841:Pia Mater / Q000098:blood supply; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology; D013552:Swine; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D001152:Arsenicals; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; C029341:oxophenylarsine; D014638:Vanadates; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases