Ümit Kemal Şentürk

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.

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.

Effect of magnesium on vascular reactivity in NOS inhibition-induced hypertension.

This study investigated the effect of magnesium on the vascular reactivity of conduit and resistance arteries in a nitric oxide synthase inhibition-induced hypertension model. The aorta and third-order branches of the mesenteric artery were dissected from normotensive control and hypertensive rats, and their constriction and dilation responses in physiological saline solution containing normal (1.2 mM) or high (4.8 mM) magnesium concentrations were examined. The responses of the vessels were evaluated using potassium chloride (KCl) and phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside. The Phe-induced constriction response of the aortic rings increased, whereas the ACh-induced dilation response decreased, in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium did not alter these responses in either group. Both the KCl- and Phe-induced constriction responses of the mesenteric arteries increased, and the ACh-induced dilation response decreased in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium significantly decreased the KCl and Phe-induced constriction and increased the ACh-induced dilation response of the mesenteric arteries in the hypertensive group, while it did not alter these responses in controls. This study suggests that high magnesium improves vascular reactivity of resistance-, but not conduit-type arteries in the nitric oxide synthase inhibition-induced hypertension model.

Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model

Abstract The aim of this study was to assess the effect of oral magnesium supplementation (Mg-supp) on blood pressure (BP) and possible mechanism in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension and/or Mg-supp were created by N-nitro-l-arginine methyl ester (25 mg/kg/day by drinking water) and magnesium-oxide (0.8% by diet) for 6 weeks. Systolic BP was measured weekly by tail-cuff method. The effects of hypertension and/or Mg-supp in thoracic aorta and third branch of mesenteric artery constriction and relaxation responses were evaluated. NOS-inhibition produced a gradually developing hypertension and the magnitude of the BP was significantly attenuated after five weeks of Mg-supp. The increased phenylephrine-induced contractile and decreased acetylcholine (ACh)-induced dilation responses were found in both artery segments of hypertensive groups. Mg-supp was restored ACh-relaxation response in both arterial segments and also Phe-constriction response in thoracic aorta but not in mesenteric arteries. The contributions of NO, prostaglandins and K+ channels to the dilator response of ACh were similar in the aorta of all the groups. The contribution of the NO to the ACh-mediated relaxation response of mesenteric arteries was suppressed in hypertensive rats, whereas this was corrected by Mg-supp. The flow-mediated dilation response of mesenteric arteries in hypertensive rats failed and could not be corrected by Mg-supp. Whereas, vascular eNOS protein and magnesium levels were not changed and plasma nitrite levels were reduced in hypertensive rats. The results of this study showed that Mg-supp lowered the arterial BP in NOS-inhibition induced hypertension model by restoring the agonist-induced relaxation response of the arteries.

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.

Comparison of Tc-99m HIG and Ga-67 citrate in the evaluation of bacterial abscess in a rat model

Tc-99m labeled polyclonal human immunoglobulin (HIG) has been shown to be able to localize an inflammatory site. There are several possible explanations for HIG accumulation at focal infection sites such as increased vascular permeability, binding of the Fc part of Ig to Fc receptors of leucocytes and binding directly to bacteria. In this study, we compared Tc-99m HIG and Ga-67 citrate scintigraphy in localizing acute bacterial abscesses induced byE. coli andS. aureus. Serial scintigrams were performed at 1, 4, 24 hr after injection. Tc-99m HIG showed greater accumulation at all times with both infectious agents than Ga-67 citrate (p < 0.05). While Tc-99m HIG showed greater accumulation inS. aureus thanE. coli (p < 0.05), there was no statistically significant difference betweenE. coli andS. aureus (p > 0.05) by Ga-67 citrate. Our study suggests that Tc-99m HIG is a superior agent to Ga-67 and bacterial affinity can be a factor responsible for HIG accumulation at focal sites of inflammation.

Effect of cadmium-induced lipid peroxidation on EEG spectral components.

Pregnant Swiss albino rats were divided into control (C) and cadmium (Cd) groups. Control animals received tap water while the Cd group received Cd as CdCl2 in their drinking water. The rat pups were separated from their mothers 22 days after birth. 78 young rats were divided into two main groups: controls (C1, C2, C4) and cadmium groups (Cd1, Cd2, Cd4). Each sub-group included 13 rats. On postnatal days 30, 60, and 120, spectral analysis of EEGs recorded from the parietal lobes of all groups of rats was computed by fast Fourier transform (FFT) algorithm. The amplitude maxima were found to occupy the frequency bands of 1-2, 2-4, 4-6, 6-8, 8-16, and 16-30 Hz. The decibel (dB) values of the maxima were significantly decreased in Cd1 and Cd2 groups compared with the corresponding control groups in all the frequency bands except 16-30 Hz. A significant amplitude (dB) decrease was observed in all the frequency bands of the Cd4 group compared with the C4 group.

The effect of pre and postnatal cadmium exposure on somatosensory evoked potentials: relation to lipid peroxidation.

Pregnant swiss albino rats were divided into three groups: control (C), gestational exposure of cadmium (G-Cd) and gestational/postnatal exposure of cadmium (GP-Cd) groups. Control animals received tap water and the rats of GP-Cd group received Cd as CdCl2 in their drinking water during the experimental period. G-Cd group was given Cd during pregnancy, but given tap water after birth. Twenty-two days after birth, 15 rats (for each group) were taken from their mothers and continued to be treated with Cd (GP-Cd group) or tap water (C and G-Cd groups) for an additional 38 days. On postnatal day (PND) 60, somatosensory evoked potentials (SEPS) of three groups were recorded following left posterior tibial nerve (PTN) stimulation. The mean latencies of N1, P1, and N2, components were significantly prolonged in both Cd groups compared with control group. The mean latency of N1 in the GP-Cd group was longer than control and the G-Cd groups. There was no significant amplitude differences among groups. On the other hand, thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation, were increased in the sciatic nerves of both groups compared with control group. A significant increase in the TBARS level of the brain was found only in GP-Cd group due to significant accumulation of Cd.

The Renin–Angiotensin System, Not the Kinin–Kallikrein System, Affects Post-Exercise Proteinuria

Background/Aims: Temporary proteinuria post-exercise is common and is caused predominantly by renal haemodynamic alterations. One reason is up-regulation of angiotensin II (Ang II) due to the reducing effect of angiotensin-converting enzyme (ACE) inhibitors. However, another, ignored, reason could be the kininase effect of ACE inhibition. This study investigated how ACE inhibition reduces post-exercise proteinuria: by either Ang II up-regulation inhibition or bradykinin elevation due to kininase activity inhibition. Methods: Our study included 10 volunteers, who completed 3 high-intensity exercise protocols involving cycling at 1-week intervals. The first protocol was a control arm, the second evaluated the effect of ACE inhibition and the third examined the effect of angiotensin type 1 receptor blockade. Upon application, both agents reduced systolic and diastolic blood pressure; however, there were no statistically significant differences. In addition, total protein, microalbumin and β2-microglobulin excretion levels in urine specimens were analysed before, 30 min after and 120 min after the exercise protocols. Results: Total protein levels in urine samples were elevated in all 3 protocols after 30 min of high-intensity exercise, compared to baseline levels. However, both ACE inhibition and angiotensin type 1 receptor blockade suppressed total protein in the 30th min. In each protocol, total protein levels returned to the baseline after 120 min. Urinary microalbumin and β2-microglobulin levels during the control protocol were significantly higher 30 min post-exercise; however, only angiotensin type 1 receptor blockade suppressed microalbumin levels. Conclusion: The results indicated Ang II up-regulation, not bradykinin elevation, plays a role in post-exercise proteinuria.