Classic Preconditioning Decreases the Harmful Accumulation of Nitric Oxide During Ischemia and Reperfusion in Rat Hearts

Abstract

Background-The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor. Methods and Results-Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes' duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 mol/L N G -nitro-L-arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/reperfusion-induced functional depression and NO accumulation were abolished. When 4.6 mol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 mol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts. Conclusions-Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2)

The protective effects of Polygonum multiflorum stilbeneglycoside preconditioning in an ischemia/reperfusion model of HUVECs

“…The protective effects of Polygonum multiflorum stilbeneglycoside preconditioning in an ischemia/reperfusion model of HUVECs Li- npg a prominent role in the signaling pathway of ischemic and drug-induced preconditioning [7][8][9] . Recent studies have demonstrated that the NO produced by inducible NO synthases (iNOS) can protect the heart, and that this effect involves K + ATP channels and contractile fibers [10,11] .…”

Mechanism and consequences of the shift in cardiac arginine metabolism following ischaemia and reperfusion in rats

“…Furthermore, although it is unlikely that an induction of arginase expression leads to a functional active enzyme within minutes our data show that we can attenuate the formation of oxidiative stress by inhibition of arginase. The most likely explanation for these acute effects are eNOS uncoupling at the time of reperfusion (10,11). Our finding that arginase-1 is strongly induced in vitro suggests that local mechanisms may trigger this increase.…”

“…However, the post-ischaemic myocardium has a characteristic loss of NO-dependent signalling (10,11). This is mainly due to an increased oxidative stress and diminished NO formation rather than the impaired downstream signalling of NO, because administration of NO donors restores a normal NO-dependent signalling (12).…”

Real-Time Monitoring of Nitric Oxide Dynamics in the Myocardium: Biomedical Application of Nitric Oxide Sensor

“…Tissue acidosis occurring during ischemia increases NO production independent from eNOS [13], and even at normal pH, xanthine oxidase in the presence of low pO 2 and high nicotinamide adenine dinucleotide (NADH) concentration is capable of producing NO from nitrite [14]. Besides, in the isolated rat heart [15] and in rabbit hindlimb muscle [16], the NO concentration is still increased during ischemia after complete NOS inhibition by Nw-nitro-L-arginine (L-NNA).…”