Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids

László Hortobágyi, Béla Kis, András Hrabák, Béla Horváth, Gergely Huszty, Horst Schweer, Balázs Benyó, Péter Sándor, David W. Busija, Zoltán Benyó

Research output: Article

15 Citations (Scopus)

Abstract

The aim of our study was to investigate the adaptation of the hypothalamic circulation to chronic nitric oxide (NO) deficiency in rats. Hypothalamic blood flow (HBF) remained unaltered during chronic oral administration of the NO synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 1 mg/ml drinking water) although acute NOS blockade by intravenous l-NAME injection (50 mg/kg) induced a dramatic HBF decrease. In chronically NOS blocked animals, however, acute l-NAME administration failed to 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. In order to clarify the potential involvement of vasodilator prostanoids in this adaptation, cyclooxygenase (COX) mRNA and protein levels were determined in the hypothalamus, but none of the known isoenzymes (COX-1, COX-2, COX-3) showed upregulation after chronic NOS blockade. Furthermore, levels of vasodilator prostanoid (PGI2, PGE2 and PGD2) metabolites were also not elevated. Interestingly, however, hypothalamic levels of vasoconstrictor prostanoids (TXA2 and PGF) decreased after chronic NOS blockade. COX inhibition by indomethacin but not by diclofenac decreased the HBF in control animals. However, neither indomethacin nor diclofenac induced an altered HBF-response after chronic l-NAME treatment. Although urinary excretion of PGI2 and PGE2 metabolites markedly increased during chronic NOS blockade, indicating COX activation in the systemic circulation, we conclude that the adaptation of the hypothalamic circulation to the 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.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalBrain research
Volume1131
Issue number1
DOIs
Publication statusPublished - febr. 2 2007

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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  • Cite this

    Hortobágyi, L., Kis, B., Hrabák, A., Horváth, B., Huszty, G., Schweer, H., Benyó, B., Sándor, P., Busija, D. W., & Benyó, Z. (2007). Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids. Brain research, 1131(1), 129-137. https://doi.org/10.1016/j.brainres.2006.11.009