Interactions between the nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways in the regulation of cerebrocortical and hypothalamic circulation
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1
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Hungary
NO plays an essential role in the regulation of cerebral blood supply. In our study we aimed to investigate the role of COX metabolites in the adaptation of the cerebral circulation to NO deficiency. Hypothalamic (HBF) and cerebrocortical blood flow (CBF) was determined in anesthetized adult male Wistar rats with the H2-clearance method or laser-Doppler flowmetry, respectively. HBF remained unaltered during chronic oral administration of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) although acute NOS blockade by intravenous L-NAME injection induced a dramatic HBF decrease. In chronically NOS blocked animals, however, acute L-NAME administration did not influence the HBF. Reversal of chronic NOS blockade by intravenous L-arginine infusion evoked significant hypothalamic hyperemia suggesting the appearance of a compensatory vasodilator mechanism in the absence of NO. However, levels of vasodilator prostanoid (PGI2, PGE2 and PGD2) metabolites were not elevated in the hypothalamus of chronically NOS blocked animals while levels of vasoconstrictor prostanoids (TXA2 and PGF2α) decreased. COX inhibition by indomethacin but not by diclofenac decreased the HBF in control rats. However, neither indomethacin nor diclofenac induced an altered HBF-response after chronic L-NAME treatment. Similarly, indomethacin did not aggravate the effect of acute NOS blockade on the CBF although L-NAME increased the levels of PGI2 and PGE2 in the cerebrospinal fluid. We conclude that the adaptation of the cerebral circulation to reduction of NO synthesis is independent of vasodilator prostanoids. Reduced release of vasoconstrictor prostanoids, however, may contribute to the normalization of HBF after chronic loss of NO.
Supported by OTKA K62375 and NKTH H07-BEL74286 grants.
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Pathophysiology and neurology - degenerative disorders
Citation:
Hortobagyi
L,
Lacza
Z,
Horvath
B,
Horvath
ME,
Sandor
P and
Benyo
Z
(2009). Interactions between the nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways in the regulation of cerebrocortical and hypothalamic circulation.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.153
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Received:
05 Mar 2009;
Published Online:
05 Mar 2009.
*
Correspondence:
Laszlo Hortobagyi, Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary, hortobagyi@elet2.sote.hu