Role of heme oxygenase and nitric oxide synthase pathways and their interactions in the regulation of the cerebral circulation.  Page description

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Details of project

  
Identifier
37386
Type K
Principal investigator Benyó, Zoltán
Title in Hungarian A hem-oxigenáz és a nitrogén monoxid szintáz reakcióutak szerepe és kölcsönhatásai az agyi vérkeringés szabályozásában
Title in English Role of heme oxygenase and nitric oxide synthase pathways and their interactions in the regulation of the cerebral circulation.
Panel Cellular and Developmental Biology
Department or equivalent Clinical Research Dept. (Semmelweis University)
Participants Erdos, Benedek
Hortobágyi, László
Horváth, Béla András
Horváth, Eszter Mária
Komjáti, Katalin
Lacza, Zsombor
Sándor, Péter
Starting date 2002-01-01
Closing date 2005-12-31
Funding (in million HUF) 9.024
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
Megállapítottuk, hogy az endogén CO kettős hatást fejt ki az agyi véráramlására: egyfelől prosztanoidok által közvetített vazodilatációt vált ki, másrészt viszont gátolja az NO szintézisét és így vazokonstrikciót okoz. Leírtuk továbbá az agyi vérkeringés alkalmazkodási képességét az NO hiányához, valamint igazoltuk hogy e folyamat független a hemoxigenáz és ciklooxigenáz reakcióutaktól. NO hiányában az agyi erek érzékennyé válnak a tromboxán A2 vazomóciót kiváltó hatásával szemben, ami az agyi véráramlás oszcillációjához és vazospazmus kialakulásához vezethet különböző kórélettani állapotokban. Leírtuk a prosztaciklin kompenzációs szerepét a koronária-keringés területén NO-hiányában. Igazoltuk, hogy a nikotinsav-okozta flush-reakció a PUMA-G receptorok által aktivált immunsejtekből történő prosztaglandin D2- és E2-felszabadulás következménye.
Results in English
Our studies have shown that endogenous carbon monoxide (CO) has a dual influence on the cerebral circulation: on one hand it induces prostanoid-mediated vasodilation but on the other hand reduces the blood flow by inhibition of nitric oxide (NO) synthesis. Furthermore, we have demonstrated the ability of the cerebral circulation to compensate the loss of NO availability and that this compensation does not involve the heme oxygenase or cyclooxygenase pathways. In the absence of NO the cerebral vessels become vulnerable to thromboxane A2-induced vasomotion which may lead to cerebrocortical blood flow oscillations and vasospasm in certain pathophysiological states. In the coronary circulation prostacyclin was shown to act as a compensatory mediator in the absence of NO. We have shown that nicotinic acid-induced flushing is mediated by PUMA-G receptor-dependent production of prostaglandin D2 and E2 by bone marrow derived immune cells.
Full text http://real.mtak.hu/186/
Decision
Yes





 

List of publications

  
Horváth B, Hrabák A, Káldi K, Sándor P, Benyó Z: Contribution of the heme oxygenase pathway to the maintenance of the hypothalamic blood flow during diminished NO synthesis., Journal of Cerebral Blood Flow and Metabolism 2003; 23: 653-657, 2003
Lacza Z, Dézsi L, Káldi K, Horváth EM, Sándor P, Benyó Z: Prostacyclin-mediated compensatory mechanism in the coronary circulation during acute NO syntase blockade., Life Sciences 2003; 73: 1141-1149, 2003
Horváth B, Őrsy P, Benyó Z: Endothelial NOS-mediated relaxations of isolated thoracic aorta of the C57BL/6J mouse: a methodological study., Journal of Cardiovascular Pharmacology, 2005; 45: 225-231, 2005
Benyó Z, Lacza Z, Hermán P, Görlach C, Hortobágyi T, Sándor P, Wahl M: Interplay between cyclic GMP- and thromboxane receptor-mediated mechanisms in the rat middle cerebral artery (MCA)., Acta Physiologica Hungarica, 2002; 89: 56, 2002
Horváth B, Hrabák A, Káldi K, Johnson FK, Sándor P, Benyó Z: The role of endogenous carbon monoxide (CO) and its interaction with nitric oxide (NO) in the cerebral circulation., Acta Physiologica Hungarica, 2002; 89: 58, 2002
Lenzsér G, Hermán P, Komjáti K, Sándor P, Benyó Z: Nitric oxide synthase blockade sensitizes the cerebrocortical circulation to thromboxane-induced CBF oscillations., Journal of Cerebral Blood Flow and Metabolism, 2003; 23: S88, 2003
Horváth B, Ishiguro M, Hrabák A, Káldi K, Lacza Z, Sándor P, Benyó Z: Interaction between the heme oxygenase and nitric oxide pathways in the regulation of the resting CBF., Journal of Cerebral Blood Flow and Metabolism, 2003; 23: S77, 2003
Ishiguro M, Lacza Z, Horváth EM, Járai Z, Sándor P, Benyó Z: The cannabinoid receptor antagonist AM-251 enhances the cerebrocortical hyperemic response to hypoxia/hypercapnia., The FASEB Journal, 2004; 18: A199.16, 2004
Horváth B, Ishiguro M, Lenzsér G, Hermán P, Hrabák A, Káldi K, Sándor P, Benyó Z: Interaction between the heme oxygenase (HO) and NO synthase pathways in the regulation of the resting CBF., The FASEB Journal, 2004; 18: A268, 2004
Horváth B, Ishiguro M, Hortobágyi L, Lenzsér G, Hermán P, Hrabák A, Káldi K, Sándor P, Benyó Z: Role of the heme oxygenase pathway int he regulation of the resting CBF., Acta Physiologica Hungarica, 2004; 91: 302-303, 2004
Ishiguro M, Lacza Z, Horváth EM, Járai Z, Sándor P, Benyó Z: Role of cannabinoid 1 receptor in the modulation of the cerebrocortical hyperemic response to hypoxia/hypercapnia., Acta Physiologica Hungarica, 2004; 91: 311-312, 2004
Őrsy P, Horváth B, Offermanns S, Benyó Z: Endothelium-dependent relaxation of the mouse thoracic aorta., Acta Physiologica Hungarica, 2004; 91: 343-344, 2004
Ishiguro M, Lacza Z, Horváth EM, Járai Z, Sándor P, Benyó Z: Inhibition of the cannabinoid-1 receptor enhances the cerebrocortical hyperemic response to hypoxia/hypercapnia., Journal of Cerebral Blood Flow and Metabolism, 2005; 25: S189, 2005
Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S: GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing., Journal of Clinical Investigation, 2005; 115: 3634-3640, 2005
Hortobágyi L, Kis B, Hrabák A, Horváth B, Sándor P, Busija DW, Benyó Z: Adaptation of the hypothalamic blood flow to chronic nitric oxide synthase blockade., Journal of Cerebral Blood Flow and Metabolism, 2005; 25: S206, 2005
Horváth B, Hortobágyi L, Sándor P, Benyó Z: Interactions between the heme oxygenase, cyclooxygenase and nitric oxide synthase pathways in the regulation of the resting hypothalamic blood flow., Journal of Cerebral Blood Flow and Metabolism, 2005; 25: S187, 2005
Leszl-Ishiguro M, Horváth B, Lenzsér G, Hermán P, Horváth EM, Sándor P, Benyó Z: Influence of the heme oxygenase pathway on the cerebrocortical blood flow under physiological conditions and during hypoxia/hypercapnia., Brain Research Bulletin, 2006; submitted for publication, 2006
Hortobágyi L, Kis B, Hrabák A, Horváth B, Huszty G, Schweer H, Benyó Z, Sándor P, Busija DW, Benyó Z: Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of the cyclooxygenase pathway., Brain Research, 2006; submitted for publication, 2006
Horváth BA, Őrsy P, Benyó Z: Endothelial-dependent relaxations of the mouse thoracic aorta., The FASEB Journal, 2005; 19: A878.5, 2005



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