Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute no-deficiency in rats

Béla Horváth, Gábor Lenzsér, Balázs Benyó, Tamás Németh, Rita Benko, András Iring, Péter Hermán, Katalin Komjáti, Zsombor Lacza, Péter Sándor, Zoltán Benyó

Research output: Contribution to journalArticle

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Abstract

Background: Low frequency (4-12 cpm) spontaneous fluctuations of the cerebrovascular tone (vasomotion) and oscillations of the cerebral blood flow (CBF) have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO) suppresses constitutively the release and vascular effects of thromboxane A2 (TXA2), NO-deficiency is often associated with activation of thromboxane receptors (TP). In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. Methodology/Principal Findings: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats) and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs) both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 mg/kg iv.) to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl esther (L-NAME, 100 mg/kg iv.) resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 14862 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA2 synthesis by ozagrel (10 mg/kg iv.) attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 mM Y-27632. Conclusion/Significance: These results suggest that hypersensitivity of the TP-receptor - Rho-kinase signaling pathway contributes to the development of low frequency cerebral vasomotion which may propagate to vasospasm in pathophysiological states associated with NO-deficiency.

Original languageEnglish
Article numbere14477
JournalPLoS One
Volume5
Issue number12
DOIs
Publication statusPublished - 2010

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Cerebrovascular Circulation
Thromboxane Receptors
thromboxanes
hypersensitivity
blood flow
nitric oxide
oscillation
Rats
Hypersensitivity
Nitric Oxide
Blood
receptors
rats
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
rho-Associated Kinases
Thromboxane A2
NG-Nitroarginine Methyl Ester
synthesis
Arterial Pressure
phosphotransferases (kinases)

ASJC Scopus subject areas

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

Cite this

Horváth, B., Lenzsér, G., Benyó, B., Németh, T., Benko, R., Iring, A., ... Benyó, Z. (2010). Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute no-deficiency in rats. PLoS One, 5(12), [e14477]. https://doi.org/10.1371/journal.pone.0014477

Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute no-deficiency in rats. / Horváth, Béla; Lenzsér, Gábor; Benyó, Balázs; Németh, Tamás; Benko, Rita; Iring, András; Hermán, Péter; Komjáti, Katalin; Lacza, Zsombor; Sándor, Péter; Benyó, Zoltán.

In: PLoS One, Vol. 5, No. 12, e14477, 2010.

Research output: Contribution to journalArticle

Horváth, B, Lenzsér, G, Benyó, B, Németh, T, Benko, R, Iring, A, Hermán, P, Komjáti, K, Lacza, Z, Sándor, P & Benyó, Z 2010, 'Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute no-deficiency in rats', PLoS One, vol. 5, no. 12, e14477. https://doi.org/10.1371/journal.pone.0014477
Horváth, Béla ; Lenzsér, Gábor ; Benyó, Balázs ; Németh, Tamás ; Benko, Rita ; Iring, András ; Hermán, Péter ; Komjáti, Katalin ; Lacza, Zsombor ; Sándor, Péter ; Benyó, Zoltán. / Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute no-deficiency in rats. In: PLoS One. 2010 ; Vol. 5, No. 12.
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AU - Németh, Tamás

AU - Benko, Rita

AU - Iring, András

AU - Hermán, Péter

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