Differential effects of selective and non-selective nitric oxide synthase inhibitors on the blood perfusion of ischemia-reperfused myocardium in dogs

Abstract

BackgroundNitric oxide (NO) is protective for the cardiovascular system, and excessive NO exerts negative effects on the circulatory system. This study aimed to compare the effects of selective or non-selective NO synthase (NOS) inhibitors on blood flow perfusion of ischemia-reperfused myocardium.Materials/MethodsMale mongrel dogs were randomly assigned to 4 groups: only ischemia-reperfusion (control), ischemia-reperfusion plus Nω-nitro-L-arginine methyl ester (NAME) treatment, ischemia-reperfusion plus aminoguanidine (AMD) treatment, and sham operation group. Myocardial contrast echocardiography (MCE) was performed. Blood samples were taken for measurement of NO. Background-subtracted peak videointensity (PVI) and PVI ratio in myocardium were measured.ResultsIn the NAME-treated group, the PVI at 5 min reperfusion did not significantly differ from pre-LAD-occlusion, but declined to and retained at a level obviously lower than the pre-LAD-occlusion. In the AMD-treated group, the PVI at 5 min reperfusion was significantly higher than at pre-LAD-occlusion, and then restored to and remained at the pre-LAD-occlusion level. The changes of PVI ratios in the 3 groups were similar to PVI values. In the AMD-treated group, the curve width increased in the early reperfusion, but returned to the pre-LAD-occlusion level at 90 min reperfusion. The plasma NO concentration in the NAME-treated group greatly decreased and remained low during the whole period of reperfusion. In the AMD-treated group, there were only slight increases in NO concentrations during reperfusion.ConclusionsNAME totally inhibited NO production and attenuated myocardial blood flow perfusion. Aminoguanidine significantly relieved the increase in NO production and alleviated the congestion of reperfused myocardium. Selective inhibitors of iNOS might be useful in the management of certain diseases associated with ischemia-reperfusion.

Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model

“…The role of NO during ischemia-reperfusion is complex. [22][23][24][25][26][27][28] NO can be protective in ischemic reperfusion injury, 29 by improving microcirculation, reducing activation of cell death pathways, enhancing mitochondrial function, and reducing the inflammatory response. 22,23 Some have suggested that release of NO from RBCs may improve tissue oxygenation through vasodilation.…”

Cardioprotective effect of aminoguanidine in combination with steroid therapy after blunt chest trauma

“…Particularly, it was shown that selectively effective aminoguanidine increased myocardial congestion by signifi cantly reducing the increase of NO and preventing the heart's contractile dysfunction (9,28). In an experimental study, the authors reported that cardiac dysfunction development was accompanied by an increased myocardial iNOS activity.…”

“…An excessive release of cardioprotective NO has a negative effect on the circulatory system and myocardial damage is markedly diminished by the use of selective and non-selective NOS inhibitors (9). Particularly, it was shown that selectively effective aminoguanidine increased myocardial congestion by signifi cantly reducing the increase of NO and preventing the heart's contractile dysfunction (9,28).…”

“…However, the negative impact of excessive increased amounts of NO on the circulatory system after myocardial damage has been shown in animal studies (8)(9)(10)(11). NO is produced by three nitric oxide synthase (NOS) isoforms, endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) (12).…”

“…The excessive release of NO produced by iNOS that have associated it with oxidative injury. Specifi cally, aminoguanidine, a selective iNOS inhibitor, has cardioprotective effects following an ischemic injury (9)(10)(11).…”