Nitrát tolerancia a szívizomban = Nitrate tolerance in the myocardium

2013 
Nagy dozisu nitroglicerin ismetelt alkalmazasaval vaszkularis nitrat toleranciat valtottunk ki kiserleti allatokban. Kimutattuk hogy vaszkularis nitrat toleranciaban a sziv es az aorta genexpresszios profilja elterően valtozik. A szivizom genexpresszios valtozasat egyeb szisztemas metabolikus allapotokban (metabolikus szindroma) is leirtuk. Kimutattuk, hogy az iszkemias posztkondicionalas infarktus meretet csokkentő hatasa jelentősen merseklődik vaszkularis nitrat tolerancia fennallasa eseten. Tovabba azt tapasztaltuk, hogy ez a jelenseg fuggetlen a tulelő kinazok aktivalodasatol. Kiserletes uremiaban viszont a prekondicionalas kardioprotektiv hatasa megtartott marad. Izolalt perfundalt szivekben kimutattuk, hogy mind a koronaria lekotes előtt, mind pedig a reperfuzio előtt megkezdett nitroglicerin perfuzio csokkenti a kialakulo infarktus meretet. Azonban a nitroglicerinnek ez a kardioprotektiv hatasa vaszkularis nitrat tolerancia fennallasa eseten nem volt megfigyelhető. Igazoltuk, hogy a NO-donor SNAP vedi a szimulalt iszkemia/reoxigenizacionak kitett primer szivizomsejt tenyeszeteket a sejtelhalastol, valoszinűleg reszben a cGMP-PKG jelatviteli utvonal aktivalasa reven. Tovabba kimutattuk, hogy a reperfuzio kezdeten alkalmazott szakaszos nagyfrekvencias ingerlessel is kivalthato posztkondicionalo hatas a szivben. | We have induced vascular nitrate tolerance in rats by repeated administration of high dose nitroglycerin. We have found that the gene expression profile of the heart and the aorta was differentially altered in response to the development of vascular nitrate tolerance. Alterations in cardiac gene expression were shown in other systemic metabolic conditions (i.e. metabolic syndrome) as well. We have shown that the infarct size limiting effect of ischemic postconditioning is attenuated in the state of vascular nitrate tolerance. Moreover, we have found that this phenomenon is independent of survival kinase activation. Experimental uremia. however, did not lead to the loss of ischemic preconditioning. We have demonstrated in ex vivo hearts that nitroglycerin perfusion decreased infarct size when started before coronary occlusion and also when only started before reperfusion. This cardioprotective effect of nitroglycerin was diminished in the state of vascular nitrate tolerance. We have shown that the NO-donor molecule SNAP is able to protect primary cardiomyocyte cultures against simulated ischemia/reperfusion at least in part via activation of cGMP-PKG signaling. We have found that a postconditioning effect can be induced by applying short periods of ventricular overdrive pacing at the onset of reperfusion.
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