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(1, 2) Feeding a single meal of the experimental diet induced, within 4 hours, a reduction of (BCAAs) in the muscle as well as in the brain 

(3). BCAAs, which are abundant in muscles, are needed for the maintenance of muscle tissue and appear to preserve muscle stores of glycogen (a storage form of carbohydrate that can be converted into energy) 

(4). BCAAs help prevent muscle protein breakdown during exercise 

(5) However, BCAA supplementation may be useful in special situations, such as preventing muscle loss at high altitudes 

(6) and prolonging endurance performance in the heat 

(7) The BCAAs make up, approximately, 40% of our dietary requirement for essential amino acids (EAAs) 

(8). It is reported that these amino acids are metabolized, exclusively, by extra-hepatic tissues, namely, muscles 

(9). It has been found that the EAAS constitute about one - third of the total of amino acid levels in the plasma 

(10). The increase in plasma BCAA levels in starved animal's results in part from decreased BCAA catabolism, particularly in heart and skeletal muscles, and from a net release of BCAA by the hepatic tissue 

(11). We have reported that long – term feeding of single doses of some EAAS caused significant changes in the free levels of amino acid 

(12). In vitro studies indicated that there are competitions between amino acids for the transport into tissues 

(13). It was suggested that a given amino acid may interfere with the transport of anther amino acid, without being transported itself 

(14). Studies on the cardiovascular actions of some free amino acids showed that administration of taurine, arginine, or glutamate in mammals decreases arterial blood pressure 

(15, 16) Our recent results have shown that feeding of young rats with isoleucine for 14 weeks caused significant changes in the levels of some amino acids in the heart and in the plasma 

(17). These changes may have resulted from a selective increase of the transport of the affected amino acids from some organs to the heart or/and plasma. Several mechanisms exist for the transport of amino acids across cell membranes. The Gamma glut amyl cycle is one example for the group transferring mechanism of amino acid transport Thus, Such uptake and transport may result from the activation of the enzyme γGT and glutathione, both of which are present in the heart and are implicated in amino acid uptake and transport across cell membranes [14]. In addition, the chronic intake of isoleucine that induced changes may affect de novo synthesis and / or enhanced transport of the affected amino acids perhaps via stimulating Growth Hormone (GH) 

[18]. It is noteworthy to indicate that glutamine and alanine were elevated in the cardiac tissues in the treated animals. Indeed, it has been reported that the branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) are the major nitrogen source for glutamine and alanine synthesis in muscle 

[19]. Branched-chain amino acid metabolism in skeletal muscle promotes the production of alanine 

[ 20]. Furthermore, other study, in vitro, indicated that isoleucine and valine enhanced production of both alanine and glutamine in cardiac muscle from fasted rats and rabbits, by contrast, leucine increased the production of glutamine, but not of alanine 

[21] The results our present study also indicate that aspartate and glutamine are significantly increased in the heart after chronic treatment concomitant with complete abolishing of arginie. L. -Aspartate has been found to be an important intermediary metabolite in the heart and has also been implicated in myocardial protection 

[22]. The use of aspartate, the substrates of cytosolic aspartate aminotransferase, for myocardial protection against hypoxia/ re oxygenation stress was suggested 

[23] further, it has been reported that increased aspartate transporter expression and activity in hypertrophy helps facilitate aspartate entry into hypertrophied cardiomyocytes, which in turn leads to improved myocardial protection. This improvement was associated with a greater preservation of ATP, glutamate and glutamine and less lactate production during ischemia in aspartate-treated hypertrophied hearts compared to all other experimental groups 

[24]. In addition, it was found that aspartate might help to relieve the inhibition of glycolysis during global myocardial ischemia and improve post-ischemic mechanical recovery in isolated rat hearts 

[25]. Moreover, administration of aspartate or glutamate protects the myocardium and induces recovery of cardiac functions during experimentally induced myocardial ischemia [15]. It was found that the possible uses of glutamine in maintaining cardiac function preoperatively and in promoting glycogen metabolism 

[26] It has also shown that in the perfused working heart of the rat, there is a substantial fall in intramuscular glutamine especially after ischemia. Also, glutamine was able to rescue the performance of the post ischemic heart. This ability appears to be connected to the ability to sustain intracardiac ATP, phosphocreatine and glutathione 

[27] Indeed (GLN) has been reported to have beneficial effects on protection against myocardial ischemia and reperfusion (I/R). I/R injury may occur via preservation of tissue metabolism and ATP content, preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis; it has beneficial effects on all of these protective pathways. Thus, the authors hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced 

[28]. Furthermore, it was reported that glutamine may prove beneficial as a protective therapy in patients undergoing procedures requiring cardiopulmonary bypass and patients with coronary artery disease 

[29]. It was also suggested that glutamine may be cardioprotective in patients with coronary heart disease 

[30] In the heart, the ability of histidine to act as an electron donor results in improving heart function during heart attack and cardiac procedures such as angioplasty, heart bypasses and heart transplants histidine has a vasodilating effect, thus making blood flow to the heart muscle. The previous studies have demonstrated that intracellular H+ buffering can be achieved by various buffers, with a resultant delay in the loss of ATP content during ischemia. In particular, histidine buffering in cardioplegia exerts a profound protective effect on the heart in association with a sustained intracellular alkalosis 

[31, 32]. Histidine is a potent proton buffer at physiological pH (pKa=6.8 at 25°C) and is the amino acid most responsible for the intrinsic intracellular buffering capacity. Its ability to enter the myocardial cell and maintain a high buffering capacity makes it an ideal agent to maintain intracellular pH at physiological range during ischemia 

[33, 34]. Administration of a high concentration of histidine through the coronary vessels may also be beneficial, because of its ability to facilitate proton removal from the cytosol by anionic carriers such as lactate. Thus, histidine facilitates removal of both H+ and lactate from the cytosol, which in turn prevents inhibition of glycolysis by the accumulation of these end products. Other beneficial effects of histidine may be related to its ability to bind calcium, which has been shown to increase in the cytosol during ischemia. There is also evidence that histidine can scavenge singlet oxygen, which may be produced during ischemia/reperfusion 

[35]. Moreover, histidine has been proven for protection of the dilated heart during prolonged ischemia in open heart operations 

[36] Arginine, however, was not detected in the treated heart tissues It is worthy to note, nonetheless, that isoleucine caused significant elevation in some heart amino acids among those amino acids is lysine and histidine It was suggested that there are separate systems for the transport of the two basic amino acids; arginine and histidine [14]. Furthermore, sometimes one amino acid can cancel the effect of another. For example, arginine is reported to have an antagonistic relationship with lysine 

[37] Therefore, this effect in cardiac arginine may be due to the significant increase in the content of cardiac lysine. In contrast, isoleucine provoked a significant elevation in the plasma level of arginine. Thus the elevations in the plasma arginine may result from the transport of cardiac arginine in the treated group in response to chronic intake of isoleucine. Arginine (2-amino-5-guanidinovaleric acid) is an amino acid that serves many heart-healthy functions. Evidence suggests that arginine may help regulate cholesterol levels 

[38]. Besides arginine appears to act as a natural blood thinner by reducing platelet aggregation 

[39]. It may also preserve the elasticity of blood vessels through antioxidant actions. In addition, L-Arginine is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system, Nitric oxide is a molecule of gas that penetrates cells and regulates their functioning, and can help to control blood pressure, which the body uses to keep blood vessels dilated, allowing the heart to receive adequate oxygen.

[40]. Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis.

[41]. Rabbits fed high cholesterol diet have increased leukocyte adhesion, which prevented by L-arginine supplementation. Platelets derived from hypercholesterolemic patients and rabbits show in vitro an enhanced tendency to aggregate [39, 42]. It has been demonstrated that L-arginine, the substrate of endogenous NO synthase, reverses the enhanced platelet aggregation in hypercholesterolemia in vitro suggests that reduced production or bioavailability of NO is involved in hypercholesterolemia-induced thromboembolic processes [39, 42]. 

In addition, L-Arginine also improves endothelium-dependent vasodilatation in humans with hypercholesterolemia and atherosclerosis, given to patients with early stages of heart disease arginine prevents the disease from getting worse and relieves chest pain and improves clinical symptoms of cardiovascular disease in man 

[43]. It has been demonstrated that administration of L-arginine can improve endothelium-dependent vascular relaxation through the release of NO [41]. In conclusion Our new observations ( 16 ) indicated that there are mobilization of the protective amino acids in the cardiac tissue associated with abolished of arginine in the cardiac tissues and that concomitant with an increase in free arginine in the plasma. These changes are generating metabolic events, which may be act as endogenous regulator for cardiac amino acids balance and that remains important from a physiological standpoint in myocardium metabolism and function.. On broad basis, these findings of the current study provide physiological data together with the publications of the role of those amino acids on the mycardiac tissue indicate that isoleucine may be beneficial particularly in protecting the myocardium against insulting stress and other stimuli that precipitate ischemia and arrhythmias and these result also explain the fact that isoleucine is involved in stress, energy and muscle metabolism References 

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