Coenzyme Q10 and exercise training reinstate middle cerebral artery occlusion-induced behavioral deficits and hippocampal long-term potentiation suppression in aging rats.

RATIONAL: Patients experience post-stroke cognitive impairment during aging. To date, no specific treatment solution has been reported for this disorder. OBJECTIVE: The purpose of this study was to evaluate the effects of exercise training and coenzyme Q10 supplementation on middle cerebral artery occlusion (MCAO) induced behavioral impairment, long-term potentiation inhibition and cerebral infarction size in aging rats. METHODS: Fifty aging male rats underwent MCAO surgery and were randomly distributed in to the following groups: 1-Sham, 2- control, 3- Coenzyme Q10, 4- Exercise training and 5- Exercise training with Q10 supplementation (Ex + Q10). Aerobic training groups were allowed to run on a treadmill for 12 weeks. Q10 (50 mg/kg) was administered intragastrically by gavage. Morris water maze, shuttle box and elevated plus maze tests were used to evaluate cognitive function. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) in the dentate gyrus area were recorded as a result of perforant pathway electrical stimulation. RESULTS: Our study showed that Q10 and aerobic training alone ameliorate spatial memory in the acquisition phase, but have no effect on spatial memory in the retention phase. Q10 and exercise training synergistically promoted spatial memory in the retention phase. Q10 and exercise training separately and simultaneously mitigated cerebral ischemia-induced passive avoidance memory impairment in acquisition and retention phases. The EPSP did not differ between the groups, but exercise training and Q10 ameliorate the PS amplitude in hippocampal responses to perforant path stimulation. Exercising and Q10 simultaneously reduced the cerebral infarction volume. CONCLUSION: Collectively, the findings of the present study imply that 12 weeks of aerobic training and Q10 supplementation alone can simultaneously reverse cerebral ischemia induced neurobehavioral deficits via amelioration of synaptic plasticity and a reduction in cerebral infarction volume in senescent rats.

Comparison of the preconditioning effect of different exercise training modalities on myocardial ischemia-reperfusion injury.

The study of exercise preconditioning can develop strategies to prevent cardiovascular diseases and outline the efficient exercise model. However, the exercise type with the most protective effect against ischemia-reperfusion injury is unknown. In this study, we examined the effects of three kinds of exercise preconditioning on myocardial ischemia-reperfusion in adult rats and explored the possible underlying mechanisms. Male Wistar rats subjected to ten weeks of endurance, resistance, and concurrent training underwent ischemia (30 min) and reperfusion (120 min) induction. Then, infarction size, serum levels of the CK-MB, the redox status, and angiogenesis proteins (VEGF, ANGP-1, and ANGP-2) were measured in the cardiac tissue. Results showed that different exercise training modes have the same reduction effects on infarction size, but ischemia-reperfusion-induced CK-MB was lower in response to endurance training and concurrent training. Furthermore, cardiac VEGF levels increased in all three kinds of exercise preconditioning but ischemia-reperfusion-induced ANGP-1 elevated more in endurance training. The cardiac GPX activity was improved significantly through the resistance and concurrent exercise compared to the endurance exercise. In addition, all three exercise preconditioning models decreased MPO levels, and ischemia reperfusion-induced MDA was lower in endurance and resistance training. Overall, these results indicated that cardioprotection of exercise training against ischemia-reperfusion injury depends on the exercise modality. Cardioprotective effects of aerobic, resistance, and concurrent exercises are due to different mechanisms. The preconditioning effects of endurance training are mediated mainly by pervasive angiogenic responses and resistance training through oxidative stress amelioration. The preconditioning effects of concurrent training rely on both angiogenesis and oxidative stress amelioration.

The role of hypoxia related hormones responses in acute mountain sickness susceptibility individuals unaccustomed to high altitude.

Acute mountain sickness (AMS) is caused by rapid ascent to altitude (>2500 m) and remains a poorly understood pathophysiological condition. Accordingly, we investigated the relationship between acute exposure to high altitude and hypoxia related biochemical proteins. 21 healthy subjects (Female (8) and male (13), Age: 36.7±8.5, BMI: 23.2±3.1) volunteers participated in this project and fasting blood samples were taken before (sea level) and after 1 and 24-h exposure to high altitude (3,550 m). Blood oxygen saturation (SpO2), AMS status (Lake Louise Score) and serum HIF-1, Endothelin-1, VEGF and Orexin-A were measured (via ELISA) at 1, 6 and 24 h after exposure to high altitude. Pre-ascent measurement of hypoxia related proteins (Orexin-A, HIF-1, VEGF and Endothelin-1) where all significantly (<0.05) higher in the AMS-resistant individuals (No-AMS) when compared to AMS susceptible individuals (AMS+). Upon ascent to high altitude, 11 out of 21 volunteers had AMS (10.1±0.6 in AMS+ vs. 0.9±0.6 in No-AMS, P<0.05) and presented with lower resting SpO2 levels (77.7±0.4 vs. 83.5±0.3 respectively, p<0.05). Orexin-A, HIF-1, VEGF and Endothelin-1, significantly increased 24 hrs after exposure to high altitude in both AMS+ and No-AMS. The response of Orexin-A was similar between two groups, also, HIF-1 elevation 24 hrs after exposure to altitude was more in AMS+ (13% vs. 19%), but the increase of VEGF and Endothelin-1, 1 and 24 hrs after exposure to altitude in No-AMS was double that of AMS+. Hypoxia related proteins include Orexin-A, HIF-1, VEGF and Endothelin-1 may play a pathophysiological role in those who are susceptible to AMS.

Aerobic training and L-arginine supplement attenuates myocardial infarction-induced kidney and liver injury in rats via reduced oxidative stress.

INTRODUCTION: The aim of the present study was to determine the effect of exercise training and l-arginine supplementation on kidney and liver injury in rats with myocardial infarction (MI). MATERIAL AND METHODS: Four weeks after MI, 50 male wistar rats randomly divided into five followed groups: sham surgery without MI (Sham, n=10), Sedentary-MI (Sed-MI, n=10) 3: L-Arginine-MI (La-MI, n=10) 4: Exercise training-MI (Ex-MI, n=10) and 5: Exercise and L-arginine-MI (Ex+La-MI). Ex-MI and Ex+La-MI groups running on a treadmill for 10 weeks with moderate intensity. Rats in the L-arginine-treated groups drank water containing 4% L-arginine. Tissues oxidative stress and kidney and liver functional indices were measured after treatments. RESULT: Urea as a kidney function indexes, increased in Sed-MI group in compared to sham group and decreased significantly in Ex-MI and Ex+La-MI groups. The level of catalase (CAT) and glutathione stimulating hormone (GSH) of kidney were significantly lower in the MI-groups compared with the Sham group and kidney Malondialdehyde (MDA) levels increased after MI and significantly decreased in response to aerobic training and L-arginine. As well as, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as liver injury indices, increased in MI-groups and decreased by training and L-arginine. In this regards, liver MDA and CAT respectively increased and decreased in MI-groups, but aerobic training and L-arginine increased liver glutathione per-oxidase (GPx) and decreased liver MDA. CONCLUSION: These results demonstrated that kidney and liver function impaired 14 weeks after MI and aerobic training and L-arginine supplementation synergistically ameliorated kidneys and liver injury in myocardial infarction rats through oxidative stress reduction.

Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction.

Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-ß and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-ß and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11-25, 26-50, 51-75, and 76-150 µm), TGF-ß, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11-25 and 26-50 µm diameters parallel to TGF-ß overexpression. In gastrocnemius muscle, the number of arterioles/mm(2) was only increased in the 11 to 25 µm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-ß and downregulation of angiostatin in MI rats.

Synergistic effects of nitric oxide and exercise on revascularisation in the infarcted ventricle in a murine model of myocardial infarction.

It has been shown that density of microvessels decreases in the left ventricular after myocardial infarction (MI). The change of angiogenic and angiostatic factors as the main factors in revascularisation after exercise training in area at risk is not determined yet in MI. Therefore, the aim of the present study was the effect of exercise training and L-arginine supplementation on area at risk angiogenesis in myocardial infarction rat. Four weeks after surgery (Left Anterior Descending Coronary artery Ligation), myocardial infarction rats were divided into 4 groups: Sedentary rats (Sed-MI); L-arginine supplementation (La-MI); Exercise training (Ex-MI) and Exercise + L-arginine (Ex+La). Exercise training (ET) lasted for 10 weeks at 17 m/min for 10-50 min day(-1). Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. After ET and L-arginine supplementation, ventricular function was evaluated and angiogenic and angiostatic indices were measured at ~1 mm from the edge of scar tissue (area at risk). Statistical analysis revealed that gene expression of VEGF as an angiogenic factor, angiostatin as an angiostatic factor and caspase-3 at area at risk decrease significantly in response to exercise training compared to the sedentary group. The capillary and arteriolar density in the Ex groups were significantly higher than those of the Sed groups. Compared to the Ex-MI group, the Ex+La group showed a markedly increase in capillary to fiber ratio. No significant differences were found in infarct size among the four groups, but cardiac function increased in response to exercise. Exercise training increases revascularization at area at risk by reduction of angiostatin. L-arginine supplementation causes additional effects on exercise-induced angiogenesis by preventing more reduction of VEGF gene expression in response to exercise. These improvements, in turn, increase left ventricular systolic function and decrease mortality in myocardial infarction rats.

The correlation between resting serum leptin and serum angiogenic indices at rest and after submaximal exercise.

BACKGROUND: The effect of leptin as stimulant angiogenic factor has been studied. But the association of leptin levels and exercise-induced angiogenesis has not been studied. Accordingly, the researchers investigated whether there were any differences in circulating serum VEGF, MMP-2 and MMP-9 among high and low resting leptin individuals at rest or in response to submaximal exercise. MATERIALS AND METHODS: For this purpose the researchers defined two groups with high and low resting leptin levels. Fifteen subjects with high resting leptin (23.57±9.14ng/ml and Vo(2) max=29.46±3.62ml/kg.min) and fifteen subjects with low resting leptin level (1.04±0.49ng/ml and Vo(2) max=37.99±4.63ml/kgmin) exercised for 1h (1h) at 70% of Vo(2) max. Antecubital vein blood was collected at rest, immediately and 2h post exercise. Serum VEGF, MMP-2 and MMP-9 was measured by ELISA method. RESULTS: Results of the study showed that the resting serum levels of VEGF, MMP-2 and MMP-9 didn't have any correlation with basic levels of leptin. In low leptin group the levels of VEGF and MMP-2 in immediately post exercise decreased significantly, but in high leptin group, only VEGF decreased significantly. 2h post exercise; the VEGF level in the low resting leptin group was significantly lower than that of its basal level. Beside, MMP-2 in the high and low basic levels of leptin groups were significantly increased compared to that of immediately post exercise. But the amount of MMP-9 did not change significantly in response to exercise in two groups. There were not any differences in the changes of VEGF, MMP-2 and MMP-9 in response to exercise between two groups. Furthermore, resting leptin had a significant correlation with V0(2) max. CONCLUSION: The obtained results showed that the serum VEGF, MMP-2 and MMP-9 did not have any correlation with basic levels of leptin. In addition, it was concluded that levels of different resting leptin is ineffective on serum levels of VEGF, MMP-2 and MMP-9 at rest and in response to exercise in normal healthy subjects.