Effect of metabolic syndrome on vasomotor function of coronary vessels  Page description

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Details of project

  
Identifier
48837
Type F
Principal investigator Bagi, Zsolt
Title in Hungarian A metabolikus szindróma hatása a koronária erek vazomotor működésére
Title in English Effect of metabolic syndrome on vasomotor function of coronary vessels
Panel Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent Department of Clinical Physiology (University of Debrecen)
Starting date 2005-01-01
Closing date 2008-12-31
Funding (in million HUF) 3.120
FTE (full time equivalent) 2.56
state closed project





 

Final report

  
Results in Hungarian
A metabolikus szindróma (MSZ)-ban a szív koronária erek kóros működése alakul ki, aminek természete és a háttérben álló mechanizmusok nem kellően ismertek. Kutatásaimban a koronária erek elernyedési képességének elváltozásait vizsgáltam MSZ-ban szenvedő betegekben és a MSZ állatkísérletes modelljeiben. MSZ állatkísérletes modelljében (magas zsírtartalmú diétán tartott patkányok) azt találtuk, hogy a koronária erekben csökken az endothelium-függő, nitrogén monoxid (NO)-közvetítette értágulás mértéke, aminek hátterében fokozott szuperoxid anion termelés áll. Ugyanakkor kimutattuk, hogy a koronária arteriolák simaizmának NO iránti érzékenysége fokozódik ezekben az állatokban. MSZ-ban szenvedő betegek koronária ereiben ugyancsak kimutattuk, hogy fokozódik azok simaizomának NO érzékenysége. Továbbá azt találtuk, hogy MSZ-ban a koronária érfali ciklooxigenáz-2 expressziója fokozott, aminek fontos szerepet tulajdonítottunk a koronária erek dilatációs képességének fenntartásában. Eredményeink szerint MSZ-ban károsodik a koronária erek működése, azonban ezzel párhuzamosan érfali mechanizmusok aktiválódnak a koronária erek elernyedési képességének fenntartására. Ezen, ún. adaptív mechanizmusok gyógyszeres gátlása, mint például a cikloxigenáz-2 gátlók alkalmazása esetén, károsíthatja a koronária erek tágulási képességét, ami további kardiovaszkuláris rizikó fokozódást jelenthet ebben a betegcsoportban.
Results in English
Metabolic syndrome (MetS) impairs the function of coronary arteries, however, alterations in the vasomotor function of coronary vessels and the underlying mechanisms are not fully elucidated. In the project alterations in dilatory function of coronary vessels were investigated in humans and animals suffering from MetS. We found that in animals fed high fat diet (model of MetS) endothelium-dependent, nitric oxide (NO)-mediated coronary dilations were reduced due to the enhanced production of superoxide anion. Interestingly we found an enhanced NO sensitivity of coronary arterioles isolated from these animals. Correspondingly enhanced NO sensitivity of coronary microvessels was detected in patients with MetS. We have also demonstrated that in patients with MetS expression of cyclooxygenase-2 is markedly elevated in coronary arterioles, which was associated with the maintained dilator capacity of those vessels. Our results indicate that vasomotor function of coronary vessels is impaired in MetS, but several mechanisms intrinsic to vascular wall may compensate the dilatory function. A potential interference with these adaptive signaling mechanisms, such as the use of cyclooxygenase-2 inhibitors would paradoxically temper the vasodilator function of coronary microvessels and may increase cardiovascular risk in patients with MetS.
Full text http://real.mtak.hu/1875/
Decision
Yes





 

List of publications

  
Erdei N, Bagi Z, Edes I, Kaley G, Koller A.: H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in Type 2 diabetic mice., Am J Physiol Heart Circ Physiol. 292(1):H649-56., 2007
Bagi Z, Hamar P, Kardos M, Koller A.: Lack of flow-mediated dilation and enhanced angiotensin II-induced constriction in skeletal muscle arterioles of lupus-prone autoimmune mice., Lupus. 2006;15(6):326-34., 2006
Toth J, Racz A, Kaminski PM, Wolin MS, Bagi Z, Koller A.: Asymmetrical dimethylarginine inhibits shear stress-induced nitric oxide release and dilation and elicits superoxide-mediated increase in arteriolar tone., Hypertension. 2007 Mar;49(3):563-8., 2007
Toth E, Racz A, Toth J, Kaminski PM, Wolin MS, Bagi Z, Koller A.: Contribution of polyol pathway to arteriolar dysfunction in hyperglycemia. Role of oxidative stress, reduced NO, and enhanced PGH(2)/TXA(2) mediation., Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H3096-104., 2007
Kark T, Bagi Z, Lizanecz E, Pásztor ET, Erdei N, Czikora A, Papp Z, Edes I, Pórszász R, Tóth A.: Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1., Mol Pharmacol. 2008 May;73(5):1405-12., 2008
Racz A, Veresh Z, Erdei N, Bagi Z, Koller A.: Thromboxane A(2) Contributes to the Mediation of Flow-Induced Responses of Skeletal Muscle Venules: Role of Cyclooxygenases 1 and 2., J Vasc Res. 2009 Jan 21;46(5):397-405., 2009
Bagi Z, Erdei N, Papp Z, Edes I, Koller A.: Up-regulation of vascular cyclooxygenase-2 in diabetes mellitus., Pharmacol Rep. 2006;58 Suppl:52-6. Review., 2006
Erdei N, Papp Z, Pollesello P, Edes I, Bagi Z.: The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles., Br J Pharmacol. 2006 Jul;148(5):696-702., 2006
Erdei N, Toth A, Pasztor ET, Papp Z, Edes I, Koller A, Bagi Z.: High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats: role of xanthine oxidase-derived superoxide anion., Am J Physiol Heart Circ Physiol. 291(5):H2107-15., 2006
Szerafin T, Erdei N, Fulop T, Pasztor ET, Edes I, Koller A, Bagi Z.: Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus., Circ Res.99(5):e12-7., 2006
Fulop T, Jebelovszki E, Erdei N, Szerafin T, Forster T, Edes I, Koller A, Bagi Z.: Adaptation of vasomotor function of human coronary arterioles to the simultaneous presence of obesity and hypertension., Arterioscler Thromb Vasc Biol. 27(11):2348-54., 2007
Bagi Z, Erdei N, Koller A.: High intraluminal pressure via H2O2 upregulates arteriolar constrictions to angiotensin II by increasing the functional availability of AT1 receptors., Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H835-41., 2008
Jebelovszki E, Kiraly C, Erdei N, Feher A, Pasztor ET, Rutkai I, Forster T, Edes I, Koller A, Bagi Z.: High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation., Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2558-64., 2008



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