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Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries

We tested two hypotheses, first that exercise training reverses age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries and second that this improved endothelium-dependent dilation is the result of increased nitric oxide (NO) bioavailability due to increased content and phosphorylation of endothelial NO synthase (eNOS) and/or increased antioxidant enzyme content. Young (2 mo) and old (22 mo) male Fischer 344 rats were exercise trained (Ex) or remained sedentary (Sed) for 10-12 wk, yielding four groups of rats: 1) young Sed (4-5 mo), 2) young Ex (4-5 mo), 3) old Sed (24-25 mo), and 4) old Ex (24-25 mo). Soleus muscle feed arteries (SFA) were isolated and cannulated with two glass micropipettes for examination of endothelium-dependent (ACh) and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism(s) by which exercise affected dilator responses, ACh-induced dilation was assessed in the presence of N(omega)-nitro-l-arginine (l-NNA; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), and l-NNA + Indo. Results indicated that ACh-induced dilation was blunted in old Sed SFA relative to young Sed SFA. Exercise training improved ACh-induced dilation in old SFA such that vasodilator responses in old Ex SFA were similar to young Sed and young Ex SFA. Addition of l-NNA, or l-NNA + Indo, abolished the exercise effect. Immunoblot analysis revealed that extracellular superoxide dismutase (SOD) protein content was increased by training in old SFA, whereas eNOS and SOD-1 protein content were not altered. Addition of exogenous SOD, or SOD + catalase, improved ACh-induced dilation in old Sed SFA such that vasodilator responses were similar to young Sed SFA. Addition of l-NNA abolished the effect of exogenous SOD in old Sed arteries. Collectively, these results indicate that exercise training reverses age-induced endothelial dysfunction in SFA by increasing NO bioavailability and that increases in vascular antioxidant capacity may play an integral role in the improvement in endothelial function.

Effect of exercise training on resistance arteries in rats with chronic NOS inhibition

Regular exercise has blood pressure-lowering effects, as shown in different types of experimental hypertension models in rats, including the nitric oxide synthase (NOS) inhibition model. We aimed to investigate possible mechanisms implicated in the exercise effect by evaluating the vasoreactivity of resistance arteries. Exercise effects on agonist-induced vasodilatory responses and flow-mediated dilation were evaluated in vessel segments of the rat chronic NOS inhibition model. Normotensive and hypertensive rats were subjected to swimming exercise (1 h/day, 5 days/wk, 6 wk), while rats in other sedentary and hypertensive groups did not. Hypertension was induced by oral administration of the nonselective NOS inhibitor l-NAME (25 mg/kg day) for 6 wk. Systolic blood pressure, as measured by the tail-cuff method, was significantly decreased by the training protocol in exercising hypertensive rats. The vasoreactivity of resistance arteries was evaluated by both wire and pressure myography studies. An impaired nitric oxide-mediated relaxation pathway in untrained hypertensive rats led to decreased relaxation responses in vessels with intact endothelium. Exercise training significantly improved the responses to acetylcholine and flow-mediated dilation in exercise-trained hypertensive rats in parallel with a decrease in blood pressure. On the other hand contraction (norepinephrine and KCl) and relaxation (sodium nitroprusside) responses of vascular smooth muscle were not different between the groups. Vascular endothelial NOS protein expression was found to be increased in both exercising groups. In conclusion, these results revealed evidence of an increased role of the nitric oxide-dependent relaxation pathway in exercising hypertensive rats.

Nitric oxide generated by red blood cells following exposure to shear stress dilates isolated small mesenteric arteries under hypoxic conditions

Red blood cells (RBC) possess a functional nitric oxide synthase (NOS) enzyme located in the cell membrane and cytoplasm. It has previously been observed that shear stress acting on RBC activates NOS and causes enhanced NO export. The aim of the present study was to investigate the physiological importance (e.g., in local blood flow regulation) of RBC-derived NO stimulated by application of shear stress. Blood samples and arterial vessel segments were obtained from Wistar rats; RBC suspensions were adjusted to a hematocrit of 0.1 l/l using Krebs solution. In order to apply shear stress to the RBC suspensions they were continuously flowed through a small-bore glass tube for 20 minutes at a wall shear stress of 2 Pa. The RBC suspensions were then perfused through endothelium denuded small mesenteric arteries having a diameter of ~300 μm under both high oxygen (PO2 ~130 mmHg) and hypoxic conditions. Perfusion of vessel segments with sheared RBC suspensions caused a significant dilation response under hypoxic conditions but not at high oxygen levels. Incubation of RBC suspensions with the non-specific NOS inhibitor L-NAME (10-3 M) prior to shear stress application abolished this dilation response. Our results indicate that NO released from RBC due to shear stress activation of NOS results in vasodilation of vessel segments under hypoxic conditions, and strongly suggest that NO originating from RBC may have a functional role in local blood flow regulation.

Biphasic Pattern of Exercise-Induced Proteinuria in Sedentary and Trained Men

Background/Aims: Exercise-induced proteinuria is a common consequence of physical activity, although its mechanism is not clear. Oxidant stress has been proposed as one of different factors involved in postexercise proteinuria in rats. In this study we investigated whether reactive oxygen radicals generated during exercise play a role in exercise-induced proteinuria in sedentary and trained men. Methods: The validity of oxidant stress following stepwise maximal exercise on proteinuria was investigated in sedentary and trained subjects before and after antioxidant vitamin treatment (A, C, and E) for 2 months. While protein carbonyl content in serum and thiobarbituric acid reactive substances (TBARS) in erythrocytes and urine were used as oxidant stress markers, total protein, albumin, β2-microglobulin in urine were assayed for proteinuria in five consecutive specimens after exercise. Urines were collected before exercise, then 30 min, 2, 8 and 24 h postexercise. Results: Increased urinary protein levels and mixed type proteinuria were determined after 30 min of exercise in sedentary and trained subjects. Proteinuria was normalized at 2 and 8 h specimens. However, glomerular type proteinuria was identified at 24 h specimen in both groups. Oxidant stress markers were significantly elevated in sedentary and trained subjects. Antioxidant treatment prevented the increase in oxidant stress markers, urinary protein levels and the occurrence of glomerular type proteinuria after exhaustive exercise at 24 h in both groups. Conclusions: These findings suggest that the exercise-induced oxidant stress may contribute to exercise-induced proteinuria in sedentary and trained men.

Physical training increases renal injury in rats with chronic NOS inhibition.

Nitric oxide (NO) is involved in regulation of vascular tone and renal hemodynamics. Inhibition of NO synthase (NOS) by Nω-nitro-l-arginine methyl ester (L-NAME) promotes systemic hypertension and glomerular damage. Exercise is effective in reducing elevated blood pressure in hypertensive individuals and rats treated with L-NAME. We investigated the effects of regular aerobic exercise on renal injury in hypertensive rats with NOS inhibition. Adult Wistar rats were divided into four groups: sedentary or exercising, nonhypertensive (two groups) and hypertensive, sedentary or exercising (two groups). Treadmill running exercise was prolonged for 4 weeks (60 min.day− 1, 5 days/week, 20 m.min− 1, no incline), and hypertension was induced by L-NAME given orally to rats for 4 weeks (25 mg.kg− 1.day− 1 in drinking water). Blood pressure was monitored at baseline and then once a week throughout L-NAME administration. Kidney sections were examined for renal histopathology. Hypertensive animals exhibited elevated blood pressure, and exercise partly prevented this elevation. Renal injury observed as arteriolar wall thickening, focal tubular atrophy, and interstitial inflammatory infiltration was apparent in hypertensive animals, and exercise induced further renal damage in hypertensive animals. The present training protocol exacerbates renal insufficiency in NOS-blockage hypertension in rats.

Levels of zinc and magnesium in senile and diabetic senile cataractous lenses

Zinc and magnesium in serum, hair, and lens were determined in diabetic and nondiabetic patients who have been operated because of senile cataract. Both trace elements were measured by atomic absorption spectrometry, after acidic digestion of the lens and hair samples. Although there was no difference in serum, lens, and hair levels of magnesium between the two groups, the lens levels of zinc in diabetic patients (0.56±0.05 µmol/g dry weight) were significantly higher as compared with nondiabetic group (0.42±0.03 µmol/g dry weight). There was no statistically significant difference in serum and hair levels of zinc between the groups. The increased concentration of zinc in the lens of diabetic patients suggests that zinc might play a role in developmental mechanism of the diabetic senile cataract.

Potential sources of oxidative stress that induce postexercise proteinuria in rats.

Exercise-induced proteinuria is a common consequence of physical activity and is caused predominantly by alterations in renal hemodynamics. Although it has been shown that exercise-induced oxidative stress can also contribute to the occurrence of postexercise proteinuria, the sources of reactive oxygen species that promote it are unknown. We investigated the enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) as possible sources of oxidative stress in postexercise proteinuria. First, we evaluated the effect of blocking the NADPH oxidase enzyme on postexercise proteinuria. We found a significant increase in urinary protein level, kidney thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content after exhaustive exercise, and NADPH oxidase activity was induced by exercise. Rats that were treated with an NADPH oxidase inhibitor for 4 days before exhaustive exercise showed no increase in kidney TBARS or protein carbonyl derivative level and no proteinuria or NADPH oxidase activation. In the next set of experiments, we investigated the effect of XO blockage on postexercise proteinuria. Oxypurinol, an XO inhibitor was administered to rats for 3 days before exercise. Although XO inhibition significantly decreased kidney TBARS levels and protein carbonyl content in exercised rats, the inhibition did not prevent exercise-induced proteinuria. However, plasma and kidney XO activity was not induced by exercise, but rather it was suppressed under oxypurinol treatment. These results suggest that increased NADPH oxidase activity induced by exhaustive exercise is an important source of elevated oxidative, stress during exercise, which contributes to the occurrence of postexercise proteinuria.

Tissue and blood levels of zinc, copper, and magnesium in nitric oxide synthase blockade-induced hypertension

The aim of this study was to determine the levels of tissue and blood zinc (Zn), copper (Cu), magnesium (Mg) in nitric oxide (NO) synthase blockade-induced hypertension. A group of albino rats received a NO synthase inhibitor, NG-nitro-l-arginine-methyl ester (l-NAME, 60 mg/kg/d) in their drinking water for 21 d. l-NAME intake caused a progressive rise in this group’s resting mean arterial blood pressure compared to a control group (p<0.01). There were no differences between the groups with regard to tissue and blood levels of Zn or Cu; however, Mg concentrations were significantly lower in the hypertensive rats’ erythrocytes (20.2% reduction from control levels), cerebral cortex (17.0%), heart (9.1%), renal cortex (12%), renal medulla (16.7%), and in the tissues of the caval vein (23.7%), mesenteric artery (29.8%), renal artery (18.4%), and renal vein (22.1%). There were no significant Mg concentration changes in the hypertensive group’s plasma, cerebellum, liver, duodenum, or aortal tissue. These findings suggest that Mg depletion may play a role in the blood pressure rise that occurs in the model of chronic NO synthase inhibition-induced hypertension.

The Effect of Exercise Training on the Responsiveness of Renal Resistance Arteries in Rats

Abstract Blood flow to several tissues changes during an acute bout of exercise. The kidney is one of the organs that are most affected by exercise-induced blood redistribution. The aim of the present study was to investigate possible exercise-induced vascular reactivity changes in renal resistance arteries in rats. Renal resistance arteries were isolated from rats that underwent 8 weeks of swimming and sedentary control rats, and the arteries were evaluated using wire myography. Similar dilation responses to acetylcholine, bradykinin, adenosine, isoproterenol, and sodium nitroprusside were observed in both groups. The vasoconstrictive agents vasopressin, endothelin-1, potassium chloride, and thromboxane A2 also induced similar responses in both groups; however, the trained group had an increased constrictive response to norepinephrine compared to the control rats. The results of our study show that renal resistance arteries of trained rats behave differently than conduit-type renal arteries and exhibit an increased contractile response to sympathetic agonists. This finding provides supporting evidence that renal blood flow markedly decreases during exercise in trained individuals.

Effect of long-term swimming exercise on somatosensory evoked potentials in rats

The study investigated whether long-term swimming exercise prevents age-related changes in rat somatosensory evoked potentials (SEPs) and somatosensory cortex (SC) morphology. A total of 25 9-month-old rats were assigned to an exercise or control group. The exercise group swam 1 h/day five times weekly for 1 year. The results showed that long-term exercise prevented age-related changes in SEPs and SC morphology.