Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex. Am J Physiol Heart Circ Physiol 2008 Aug;295(2):H619-31
Date
05/27/2008Pubmed ID
18502903Pubmed Central ID
PMC2519225DOI
10.1152/ajpheart.01211.2007Scopus ID
2-s2.0-52449129583 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Nitric oxide (NO) modulates vasodilation in cerebral cortex during sensory activation. NO is known to inhibit the synthesis of 20-HETE, which has been implicated in arteriolar constriction during astrocyte activation in brain slices. We tested the hypothesis that the attenuated cerebral blood flow (CBF) response to whisker stimulation seen after NO synthase (NOS) inhibition requires 20-HETE synthesis and that the ability of an epoxyeicosatrienoic acids (EETs) antagonist to reduce the CBF response is blunted after NOS inhibition but restored with simultaneous blockade of 20-HETE synthesis. In anesthetized rats, the increase in CBF during whisker stimulation was attenuated after the blockade of neuronal NOS with 7-nitroindazole. Subsequent administration of the 20-HETE synthesis inhibitor N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) restored the CBF response to control levels. After the administration of 7-nitroindazole, the inhibitory effect of an EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) on the CBF response was lost, whereas the simultaneous administration of 7-nitroindazole and HET0016 restored the inhibitory effect of 14,15-EEZE. The administration of HET0016 alone had only a small effect on the evoked CBF response in rats. Furthermore, in neuronal NOS(+/+) and NOS(-/-) mice, HET0016 administration did not increase the CBF response to whisker stimulation. In neuronal NOS(+/+) mice, HET0016 also blocked the reduction in the response seen with acute NOS inhibition. These results indicate that 20-HETE synthesis normally does not substantially restrict functional hyperemia. Increased NO production during functional activation may act dynamically to suppress 20-HETE synthesis or downstream signaling and permit EETs-dependent vasodilation. With the chronic loss of neuronal NOS in mice, other mechanisms apparently suppress 20-HETE synthesis or signaling.
Author List
Liu X, Li C, Falck JR, Roman RJ, Harder DR, Koehler RCMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAmidines
Animals
Cerebral Cortex
Cerebrovascular Circulation
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Hyperemia
Indazoles
Male
Mechanotransduction, Cellular
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurons, Afferent
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Physical Stimulation
Rats
Rats, Wistar
Time Factors
Vasodilation
Vibrissae
