Exercise training enhances flow-mediated dilation in spontaneously hypertensive rats.

This study investigated the effect of exercise training on the flow-mediated dilation (FMD) in gastrocnemius muscle arteries from spontaneously hypertensive rats (SHR). SHR and WKY rats were divided into sedentary and exercised groups. After swimming exercise for eight weeks, the isolated arteries were mounted on pressurized myograph and FMD responses examined. The role of nitric oxide (NO), prostaglandins (PGs) and endothelium derived hyperpolarizing factor (EDHF) on FMD were assessed by obtaining dilation responses in the presence and absence of pharmacological antagonists. N(omega)-nitro-L-arginine methyl ester (L-NAME), indomethacin (INDO) and tetraethylamonium (TEA) were used to inhibit nitric oxide synthase, cyclooxygenase and EDHF-mediated responses, respectively. The FMD response was significantly blunted in arteries of SHR compared with WKY rats, and, improved by exercise training in SHR (SHR-ET) group. In SHR arteries, L NAME and TEA did not affect dilation responses to flow, while INDO led to a significant enhancement in this response. Although dilation response was not altered by L-NAME in arteries obtained from trained SHR, TEA caused a significant attenuation and INDO led to significant increases. These results demonstrate that exercise training improves FMD in SHR, and, this enhancement induced by exercise training occurs through EDHF-mediated mechanism(s).

Plasma levels of nitrites, PGF1alpha, and nitrotyrosine in LPS-treated rats: functional and histochemical implications in aorta.

We investigated the effects of lipopolysaccharide (LPS) administration on plasma nitrite, nitrotyrosine and 6-keto prostaglandin F1alpha, (PGF1alpha) levels and the related resultant changes in function and histochemistry of aorta in rats. Plasma nitrite and PGF1alpha nitrotyrosine levels were analysed after 5 mg/kg intravenous LPS was administered to rats compared with those in non-treated rats. The distribution of nitrotyrosine in the aorta was studied immunohistochemically. The contractile responses of aortic rings to phenylephrine (PE) from both the LPS-treated and control rats were studied in the organ baths. There were increases in plasma nitrite, PGF1alpha, and nitrotyrosine concentrations of LPS-treated rats compared to non-treated rats. Immunoreactivity of nitrotyrosine residues were detected in the endothelial and smooth muscle cells in LPS-treated but not in control rat aorta. The contractile responses to PE of the LPS-treated rat aortic rings were significantly reduced as compared with those of control rat's. Incubation of the aortic rings from LPS-treated rats with cyclooxygenase inhibitor indomethacine or with a combination of indomethacine and nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) increased the contractile responses to the levels observed in control rats suggesting that both prostanoids and particularly nitric oxide (NO) are involved in the reduced contractile responses in LPS-treated rats. These results supported the view that LPS might cause an increment in both NO and PGI2 levels. This increase in the NO and PGI2 levels may be responsible from the reduction in responses of aorta to contractile agents in LPS-treated rats. Increased peroxynitrite formation in LPS-treated rats may lead to nitration of the tyrosil residues of the proteins in the aorta.

Angiotensin II inhibition attenuates postexercise proteinuria in rats.

An important explanatory theory for the mechanism of postexercise proteinuria is that angiotensin II could be inhibited by angiotensin converting enzyme inhibitors. Because of the kininase effect of the angiotensin converting enzyme, it is unclear whether the kallikrein-kinin system contributes to the effect of angiotensin converting enzyme inhibitors on postexercise proteinuria. The aim of this study was to evaluate any possible involvement of the kallikrein-kinin system in the therapeutic effect of angiotensin converting enzyme inhibitors on postexercise proteinuria. We evaluated urinary protein levels in exhausted rats receiving an angiotensin converting enzyme inhibitor (enalapril) or an angiotensin II type I receptor antagonist (losartan). Enalapril (30 mg/kg/day, two days) or losartan (20 mg/kg/day, two days) were given to animals using an intragastric catheter. Urinary protein levels increased (41 %) in rats which were exhausted via treadmill running (p < 0.05). In animals that received drug treatment (enalapril or losartan), but did not exercise to exhaustion, urinary protein levels were not different from the control group. Urinary protein levels were found to be significantly lower (p < 0.05) in animals which performed acute exhaustive exercise after enalapril or losartan administration, compared to rats which were exhausted without drug administration. Inhibition of postexercise proteinuria by either enalapril or losartan suggested that angiotensin II plays an important role in postexercise proteinuria, however, it appears the kallikrein-kinin system is not involved in angiotensin converting enzyme inhibitors effect.

The effect of one year's swimming exercise on oxidant stress and antioxidant capacity in aged rats.

The effect of exercise on oxidant stress and on alterations in antioxidant defense in elderly has been investigated extensively. However, the impact of regularly performed long-term physical activity starting from adulthood and prolonged up to the old age is not yet clear. We have investigated the changes in the activities of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) - and lipid peroxidation in various tissues of rats which had performed (old-trained) or had not performed (old-control) regular swimming exercise for one year. These animals were compared with young-sedentary rats. Increased lipid peroxidation was observed with ageing in all tissues (heart, liver, kidney, striated muscle) and swimming had no additional effect on this elevation of lipid peroxidation. Heart and striated muscle SOD activites, and striated muscle CAT activity increased as a consequence of ageing, whereas kidney and liver CAT activities, as well as GPx activities in kidney, liver, lung and heart were significantly decreased compared to young controls. Lung and heart SOD, liver CAT activities as well as GPx activities in liver, lung and heart were increased significantly in rats which performed exercise during ageing, compared to the old-control group. These findings suggest that lifelong exercise can improve the antioxidant defense in many tissues without constituting any additional oxidant stress.

Training induced alterations of visual evoked potentials are not related to body temperature.

The purpose of this study was to investigate the effect of mild chronic exercise on visual evoked potentials (VEPs). Twenty male Wistar rats were randomly divided into two groups: Control (C) and Exercise (E) groups. Exercise was performed on a motor-driven treadmill for 8 weeks. After 5 min of exercise, plasma lactic acid levels were determined. At the end of the experimental period, VEPs were recorded from E group twice: Five min (E-5 min) and 24 h (E-24 h) after the last bout of exercise. During visual evoked potential (VEP) recordings body temperature of the animals was kept constant to eliminate the effect of temperature changes. No difference was found between the lactic acid levels of two groups. The mean latencies of VEPs from E-5 min were shortened compared with the control group. The mean latencies of VEP components in E-24 h were observed to have returned to the control levels. Peak to peak amplitudes of VEPs were found to be unaltered among all measurements. We concluded that immediately after exercise, VEPs latencies were shortened independently from body temperature via unknown mechanisms. The latencies of VEPs were returned to control values after 24 h.

Exercise-induced oxidative stress affects erythrocytes in sedentary rats but not exercise-trained rats.

Oxidant stress is one of the factors proposed to be responsible for damaged erythrocytes observed during and after exercise. The impact of exertional oxidant stress after acute exhaustive treadmill running on erythrocyte damage was investigated in sedentary (Sed) and exercise-trained (ET) rats treated with or without antioxidant vitamins C and E. Exhaustive exercise led to statistically significant increments in the levels of thiobarbituric acid-reactive substance (TBARS) and H2O2-induced TBARS in Sed rats and resulted in functional and structural alterations in erythrocytes (plasma hemoglobin concentrations, methemoglobin levels, and rise in osmotic fragility of erythrocytes with decrease in erythrocyte deformability). Administration of antioxidant vitamin for 1 mo before exhaustive exercises prevented lipid peroxidation (TBARS, H2O2-induced TBARS) in Sed rats without any functional or structural alterations in erythrocytes. Parameters indicating erythrocyte lipid peroxidation and deterioration after exhaustive exercise in rats trained regularly with treadmill running for 1 mo were not different from those in Sed controls. Erythrocyte lipid peroxidation (TBARS) increased in exhausted-ET rats compared with ET controls; however, the plasma hemoglobin, methemoglobin levels, and erythrocyte osmotic fragility and deformability did not differ. Exhaustive exercise-induced lipid peroxidation in ET rats on antioxidant vitamin treatment was prevented, whereas functional and structural parameters of erythrocytes were not different from those of the ET controls. We conclude that exertional oxidant stress contributed to erythrocyte deterioration due to exercise in Sed but not in ET rats.

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, N(G)-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.

Red blood cell rheological alterations in hypertension induced by chronic inhibition of nitric oxide synthesis in rats.

Nitric oxide (NO) plays a major role in vascular regulation. Modulation of NO synthesis is known to influence blood pressure. Inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME; 72 mg/kg/day, p.o., 21 days) resulted in 60% increase in blood pressure in rats. Red blood cell (RBC) transit time measured by the cell transit analyzer increased significantly in the L-NAME treated group, in comparison to normotensive rats. RBC aggregation measured in autologous plasma, by a photometric rheoscope also increased significantly in the hypertensive rats. RBC cytosolic free calcium concentration was also significantly higher in the hypertensive animals. Incubation of RBC from hypertensive and control animals with NO donor, sodium nitroprusside (SNP; 10-1000 microM) for 60 minutes resulted in a dose-dependent decrease in RBC aggregation, however aggregation index was significantly higher in hypertensive group at each SNP concentration. Incubation with SNP had no effect on RBC deformability in the control group, while a slight decrease in RBC transit time was observed only at 10 microM SNP in the hypertensive group. These results imply that NO may play a role in the regulation of rheological properties of RBC and the alterations in these properties may at least in part be involved in the development of L-NAME induced hypertension.

Effects of swimming exercise on red blood cell rheology in trained and untrained rats.

Red blood cell (RBC) mechanical properties were investigated after swimming exercise in trained and untrained rats. A group of rats was trained for 6 wk (60 min swimming, daily), and another group was kept sedentary. Blood samples were obtained either within 5 min or 24 h after 60 min swimming in both groups. In the untrained rats, the RBC aggregation index decreased to 2.60 +/- 0.4 immediately after exercise from a control value of 6.73 +/- 0.18 (P < 0.01), whereas it increased to 13.13 +/- 0.66 after 24 h (P < 0.01). RBC transit time through 5-microm pores increased to 3.53 +/- 0.16 ms within 5 min after the exercise from a control value of 2.19 +/- 0. 07 ms (P < 0.005). A very significant enhancement (166%) in RBC lipid peroxidation was detected only after 24 h. In the trained group, the alterations in all these parameters were attenuated; there was a slight, transient impairment in RBC deformability (transit time = 2.64 +/- 0.13 ms), and lipid peroxidation was found to be unchanged. These findings suggest that training can significantly limit the hemorheological alterations related to a given bout of exercise. Whether this effect is secondary to the training-induced reduction in the degree of metabolic and/or hormonal perturbation remains to be determined.

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.

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.

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 developmental exposure to cadmium (Cd) on visual evoked potentials (VEPs) and lipid peroxidation.

Pregnant Swiss albino rats were divided into three groups: control (C), gestational exposure of Cd (G-Cd), and gestational/postnatal exposure of Cd (GP-Cd) groups. Control animals received tap water, and the rats of GP-Cd group received Cd as CdC12 in their drinking water during the experimental period. The 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, flash visual evoked potentials (FVEPs) were recorded with disc electrodes attached with collodion 0.5 cm in front of and behind bregma. The mean latencies on N1, P2, and P3 were prolonged in the GP-Cd group compared with controls. The mean latency of P3 was also significantly different between G-Cd and GP-Cd groups. P1-N1 and N1-P2 amplitudes of VEPs were significantly decreased in the GP-Cd group compared with control group. N1-P2 amplitude of the G-Cd group was significantly lower than that of the control group. Thiobarbituric acid reactive substances (TBARS) were determined as an indicator of lipid peroxidation. Our data showed that pre- and postnatal Cd treatment caused a significant increase of lipid peroxidation in the brain.

Effect of chronic cadmium exposure on VEP and EEG spectral components.

Pregnant swiss albino rats were divided to three groups as control (C), cadmium (Cd) and non-cadmium (NCd) groups. Control animals were received tap water while the rats of Cd group were received Cd as CdC12 in their drinking water during the experimental period. On the other hand, the NCd group was given Cd during pregnancy, but given tap water after birth. Twenty-two days after birth, fourteen rats (for each group) were taken from their mothers and continued to be treated with Cd (Cd group) or tap water (C and NCd groups) for an additional 38 days. After the experimental period, flash VEPs and EEGs of three groups were recorded and amplitude spectral analysis was computed by Transient Response-Frequency characteristics (TRFC) method. The mean amplitude (dB) of 1-3.5 and 14-20 Hz frequency bands for right response whereas 1-3.5, 4-7, 8-13 and 14-20 Hz frequency bands for left response of VEPs were decreased in Cd group compared with control group. On the other hand, significant differences were observed between Cd and control groups in all the frequency bands of EEGs except 6-8 Hz.

The effect of manganese-induced hypercholesterolemia on learning in rats.

Since the exact mechanism of manganese (Mn)-induced learning disability is not known, we investigated the role of elevated cholesterol in rats exposed daily to 357 and 714 micrograms Mn/kg for 39 d. Significant Mn accumulation was accompanied by increased cholesterol content in the hippocampal region of Mn-treated rats. The learning, which is based on the time needed to reach food placed at the exit of a T-maze after a 1-d training period, was significantly slower in exposed rats than in unexposed rats. The rats receiving 357 and 714 micrograms Mn/kg reached the food in 104.5 +/- 13.8 and 113.3 +/- 25.7 s, respectively, on d 30, whereas their untreated counterparts reached the food in 28.7 +/- 11.4 s. This delay was completely corrected to 29.3 +/- 7.8 and 30.7 +/- 6.0 s in rats with coadministration of an inhibitor of cholesterol biosynthesis with 357 and 714 micrograms/kg of Mn. The correction of impaired learning was associated with the normalization of hippocampal cholesterol, but the Mn level in this region of the brain was not influenced in rats treated with a drug that inhibits cholesterol biosynthesis. These results suggested that Mn-induced hypercholesterolemia is involved in Mn-dependent learning disability.

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 by E. coli and S. aureus. Serial scintigrams were performed at 1, 4, 24 hr after injection. Tc-99m HIG showed greater accumulation at all times with both infections agents than Ga-67 citrate (p < 0.05). While Tc-99m HIG showed greater accumulation in S. aureus than E. coli (p < 0.05), there was no statistically significant difference between E. coli and S. 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.

Role of cadmium-induced lipid peroxidation in the kidney response to atrial natriuretic hormone.

In order to investigate the role of increased lipid peroxidation in the development of cadmium-induced hypertension, 30 male albino rats were exposed to drinking water containing 15 micrograms/ml cadmium for 30 days, and the results were compared with those of 30 controls. Water containing high cadmium concentrations caused a significant accumulation of the element in blood and kidneys, associated with an obvious elevation in blood pressure. The systolic and diastolic blood pressures rose from 102.8 +/- 7.0 and 81.2 +/- 3.8 mm Hg to 128.1 +/- 4.6 and 107.9 +/- 7.4 mm Hg, respectively, in cadmium-treated rats (p < 0.01). A decreased glomerular filtration rate and increased serum creatinine levels were accompanied by elevated levels of cortical and medullary thiobarbituric acid reactive substances in cadmium-induced hypertensive rats. The mean thiobarbituric acid reactive substance level rose from a control value of 211.5 +/- 64.1 to 303.3 +/- 46.3 nmol/g protein (p < 0.01) in the renal cortex due to the high intake of cadmium. Despite its obvious diuretic and natriuretic action in control animals, the bolus injection of 1.2 and 2.4 micrograms/kg atrial natriuretic peptide corrected neither elevated blood pressure nor the reduced glomerular filtration rate in rats exposed to cadmium. However, the tubular response to atrial natriuretic peptide remained unaltered. These data suggest that a lack of vascular response to atrial natriuretic peptide is one of the many putative causes of cadmium-induced hypertension, and cadmium-mediated increased lipid peroxidation may be involved in this unresponsiveness.

Cadmium induced alterations in somatosensory evoked potentials.

Pregnant Swiss albino rats were divided into three groups: control (C), cadmium (Cd) and non-cadmium (NCd) groups. Control animals received tap water; the Cd rats received Cd as CdCl2 in their drinking water during the experimental period, while the NCd group was given Cd during pregnancy, and 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 (Cd group) or tap water (C and NCd groups) for an additional 38 days. After the treatment period, somatosensory evoked potentials (SEPs) of the three groups were recorded from central (Cz) referenced to frontal (Fz) following left posterior tibial nerve (PTN) stimulation. Amplitude spectra of SEPs were computed by fast Fourier transform (FFT) algorithm. There was a significant amplitude decrease in 1-3.5 Hz in the NCd group and 1-3.5 and 14-20 Hz frequency bands of the Cd group compared with the control group.

Cyclosporin A affects red blood cell deformability in vivo but not in vitro in guinea pig.

A hemorheological mechanism has been proposed for the hemodynamic effects of cyclosporin A (CsA). In vivo and in vitro effects of CsA on red blood cell (RBC) deformability were investigated in guinea pigs. RBC transit time, measured by a cell transit analyzer, was found to be prolonged, implying impaired deformability in guinea pigs treated with CsA (10 mg/kg/day) for 7 days. Blood CsA concentration was approximately 900 ng/ml. RBC cytosolic calcium concentration was higher in the CsA-treated groups than in the control group. RBC lipid peroxidation was not affected. Combining pentoxifylline injections (100 mg/kg/day) with CsA therapy did not prevent the effect on RBC deformability and cytosolic calcium concentration. CsA did not affect RBC transit time and cytosolic calcium concentration in vitro. Thus, the influence of CsA on RBC deformability appears to be an indirect effect that is mediated by the alterations in RBC calcium homeostasis.