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An increase in oxidative stress and decrease in antioxidant enzymes have been suggested to be involved in the pathophysiology of myocardial infarction (MI). In this study in rats, treadmill exercise training and losartan treatment began 1 week post-myocardial infarction (MI) and lasted 8 weeks. We evaluated the changes in the mRNA and protein expressions for the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase after exercise and losartan treatment post-MI. Our results demonstrated that GPx and catalase mRNA levels were comparable among all the groups, while the mRNA level for manganese SOD (MnSOD) was significantly increased in exercise training with/without losartan treatment compared with the sedentary post-MI group. Moreover, the mRNA level for gp91(phox) was dramatically decreased by a combination of exercise and losartan treatment. The protein levels for MnSOD were significantly elevated by exercise training in combination with losartan treatment. The protein levels for catalase were significantly increased in response to exercise, and further augmented by exercise together with losartan treatment. Thiobarbituric acid-reactive substances in plasma were significantly increased in the post-MI rats, but were decreased by exercise or losartan treatment, indicating that both exercise and losartan may reduce lipid oxidative damage. In addition, catalase and SOD enzymatic activities were significantly enhanced by exercise combined with losartan treatment. Our results suggest that exercise training improves catalase and MnSOD expression and attenuates oxidative stress. These effects are potentiated when combining exercise with angiotensin II receptor blockade.

To test the hypothesis that early exercise training after myocardial infarction (MI) could preserve cardiac function, alleviate left ventricular (LV) remodeling and induce a protective effect on morphology, male Sprague-Dawley rats underwent coronary ligation or sham operation, and were assigned to 3 groups: Sham, sedentary MI (SedMI), and exercise MI (ExMI). We measured the changes in collagen volume fraction, matrix metalloproteinase (MMP) 1, tissue inhibitor matrix metalloproteinase 1 (TIMP-1), angiotensin II receptor type 1 (AT1), and angiotensin converting enzyme (ACE) at gene and protein levels after 8 weeks of exercise training. Cardiac functions were determined by echocardiographic and hemodynamic measurements. Early exercise training after MI had no effect on LV wall thinning. Cardiac function was significantly preserved in the ExMI group in comparison to the SedMI group. The collagen volume fraction in the ExMI group was significantly lower than in the SedMI group. Compared to the SedMI group, the ExMI group showed a markedly decrease at both the gene and protein levels in TIMP-1 (P

We examined the effect of exercise on postprandial hypertriglyceridemia (PHTG) and insulin resistance in individuals with metabolic syndrome. Subjects were 10 hypertriglyceridemic men with insulin resistance [age = 35.0 ± 1.8 yr, body weight = 90.7 ± 3.3 kg, fasting triglyceride (TG) = 2.6 ± 0.4 mmol/l, peak oxygen consumption (V̇o2peak) = 36.0 ± 1.3 ml−1·kg−1·min−1, and homeostatic model assessment of insulin resistance (HOMA-IR)= 3.1 ± 0.3]. Each participant performed a control trial (Ctr; no exercise) and three exercise trials at 60% of their V̇o2peakfor 30 min (30 min-Ex), 45 min (45 min-Ex) and 60 min (60 min-Ex). All subjects had a fat meal in each trial. In the exercise trials, the subject jogged on a treadmill for a designated duration of 12 h before ingestion of a fat meal. Blood samples were taken at 0 h (before the meal) and at 2, 4, 6, and 8 h after the meal. The plasma TG, area score under TG concentration curve over an 8-h period (TG AUC) after the meal, and HOMA-IR were analyzed. The TG AUC scores in both the 45 min-Ex and 60 min-Ex were 31 and 33% lower, respectively, than Ctr ( P < 0.02). There were no significant differences in TG AUC scores between the 30 min-Ex and the Ctr ( P > 0.05). There were no trial differences in the fasting plasma glucose concentration ( P > 0.05). HOMA-IR values in the 30 min-Ex, 45 min-Ex, and 60 min-Ex trials were lower than the Ctr ( P < 0.03), but no significant differences were found in HOMA-IR among the exercise trials. The results suggest that for physically inactive individuals with metabolic syndrome, exercising at moderate intensity for 45 min effectively attenuates PHTG while exercise for 30 min is sufficient to improve insulin action.

We examined the effect of exercise on postprandial lipemia (PPL) and insulin resistance in individuals with metabolic syndrome. Subjects were 10 hypertriglyceridemia (HTG) males with insulin resistance [age = 40.1 +/- 2.2 years, body weight = 96.3 +/- 3.3 kg, fasting triglyceride (TG) = 263 +/- 25 mg/dl, VO(2)max = 37 +/- 1.1 ml/kg/min, and Homeostatic Model Assessment (HOMA-IR, an index of insulin resistance) = 3.05 +/- 0.40]. Each subject performed a control trial (Ctr, no exercise), and three exercise trials at 40% (40%T), 60% (60%T), and 70% (70%T) of their VO(2)max. The order of trials was randomized and there were 1-2 weeks wash-out period between the trials. All subjects had a fat-meal in each trial. In the exercise trials, subjects jogged on a treadmill for 1 h at a designated intensity 12 h prior to a fat-meal ingestion. Blood samples were taken at 0 h (before the meal), and 2, 4, 6, and 8 h after the meal. The plasma TG, area score under TG concentration curve for over an 8 h-period (TG AUC) after the meal, and HOMA-IR were analyzed. The TG AUC score in 40%T was 30% lower (P = 0.003), 60%T was 31% lower (P = 0.02), and 70%T was 39% lower (P = 0.02) than Ctr. There were no significant differences in the TG AUC scores among the exercise trials (P > 0.05). The insulin concentrations in both 60 and 70%T were lower than Ctr (P < 0.01) which did not differ from 40%T. HOMA-IR in both 60%T (P = 0.041) and 70%T (P = 0.002) were lower than Ctr, but not different from 40%T (HOMA-IR: Ctr = 3.05 +/- 0.40, 40%T = 2.67 +/- 0.35, 60%T = 2.49 +/- 0.31, 70%T = 2.21 +/- 0.27). The results suggest that for physically inactive individuals with metabolic syndrome, exercising at low to moderate intensity may be sufficient to attenuate PPL and increase insulin sensitivity, whereas higher intensity exercise may be needed to normalize blood glucose.

We studied cFos and FosB staining in the supraoptic nucleus (SON) the organum vasculosum of the lamina terminalis (OVLT) and the median preoptic nucleus (MnPO) in adult male rats after water deprivation (24 h, n = 11; 48 h, n = 12) and water deprivation with rehydration (22 h + water, n = 11; 46 h + water, n = 10). Control rats ( n = 15) had water available ad libitum. Separate sets of serial sections from each brain were processed for immunocytochemistry using primary antibodies against either c-Fos or FosB protein. Plasma osmolality, vasopressin, hematocrit, and plasma proteins were measured in separate groups ( n = 6–7). The number of c-Fos-positive cells in the SON was significantly increased after 24 and 48 h of water deprivation. In contrast, rehydrated groups were not different from control. Water deprivation significantly increased c-Fos staining in both the OVLT and the MnPO, but c-Fos staining was not altered by rehydration. FosB staining in the SON was significantly increased only by 48-h water deprivation, and this effect was significantly decreased by rehydration. In the MnPO and OVLT, FosB staining was significantly increased by water deprivation, and, like c-Fos staining, these increases were not affected by rehydration. Water deprivation significantly increased osmolality and hematocrit, as well as plasma protein and vasopressin concentrations. Plasma measurements from rehydrated rats were not different from control. We conclude that water deprivation and rehydration differentially affect c-Fos and FosB staining in a region-dependent manner.

Immunohistochemistry for Fos was used to determine the role of the superior laryngeal nerve in conscious rats following water deprivation and rehydration. Adult male rats were subjected to either unilateral superior laryngeal nerve section (SLNX) or sham surgery. Two weeks later rats from each surgical group were water deprived for 48 h or water deprived for 46 h hours and given access to water for 2 h prior to perfusion. Controls were allowed ad libitum access to water. Brains were processed for Fos using a commercially available antibody. Changes in plasma osmolality and hematocrit were not significantly different between SLNX and sham following any of the treatments. Water intake in rats was not significantly affected by SLNX. In the supraoptic nucleus (SON) of sham rats, water deprivation significantly increased Fos staining while water intake following dehydration prevented this increase. Water deprivation significantly increased Fos staining in the SON of SLNX rats. Following water intake after 46 h water deprivation in SLNX rats, Fos staining in the ipsilateral SON was significantly greater than the contralateral SON and significantly lower than 48 h water deprivation. In the nucleus of the solitary tract (NTS) of sham rats, both water deprivation and water intake produced significant increases in Fos staining bilaterally compared to euhydrated controls. In SLNX rats, water deprivation significantly increased Fos in both ipsilateral and contralateral NTS that was not different from sham rats. SLNX significantly decreased Fos staining in the ipsilateral NTS of rats given access to water after dehydration compared to the corresponding sham treated rats. Fos staining was not affected in the contralateral NTS of SLNX rats given access to water after dehydration. This suggests that the superior laryngeal nerve contributes to changes in Fos staining in the NTS and SON following water intake in dehydrated rats.

This experiment tested the role of oropharyngeal and gastric afferents on hypothalamic activation in dehydrated rats instrumented with gastric fistulas and allowed to drink water or isotonic saline compared with euhydrated controls (CON). Rats were water-deprived for 48 h (48 WD) or 46 h WD with 2 h rehydration with water (46+W) or isotonic saline (46+S). 46+W and 46+S rats were given water with fistulas open (46+WO/46+SO, sham) or closed (46+WC/46+SC). Compared with CON, water deprivation increased and water rehydration decreased plasma osmolality, while sham rehydration had no effect. Water deprivation increased c-Fos staining in the lamina terminalis. However, none of the sham or rehydration treatments normalized c-Fos staining in the lamina terminalis. Analysis of AVP and c-Fos-positive neurons in the supraoptic nucleus (SON) revealed reduced colocalization in 46+WO and 46+SC rats compared with 48 WD and 46+SO rats. However, 46+WO and 46+SC rats had higher c-Fos staining in the SON than 46+WC or CON rats. Examination of c-Fos in the perinuclear zone (PNZ) revealed that sham and rehydrated rats had increased c-Fos staining to CON, while 48 WD and 46+SO rats had little or no c-Fos staining in this region. Thus, preabsorptive reflexes contribute to the regulation of AVP neurons in a manner independent of c-Fos expression in the lamina terminalis. Further, this reflex pathway may include inhibitory interneurons in the PNZ region surrounding the SON.

Inappropriate vasopressin (AVP) release causes dilutional hyponatremia in many pathophysiological states such as cirrhosis. The central molecular mechanisms that mediate inappropriate AVP release are unknown. We tested the hypothesis that changes in the expression or trafficking of TRPV4 in the central nervous system may contribute to inappropriate AVP release in the bile duct ligation (BDL) model of cirrhosis in the rat. Four weeks after surgery, BDL rats demonstrated significantly increased plasma vasopressin and plasma renin activity (PRA), hypervolemia, and decreased plasma osmolality. These effects were blocked by providing BDL rats with 2% saline to drink for 15 days. TRPV4 protein expression was significantly increased in brain punches from BDL rats containing the supraoptic nucleus (SON) of the hypothalamus (100% ± 11 to 157% ± 4.8), and this effect was blocked in BDL rats given saline. Immunohistochemistry demonstrated a significant increase in TRPV4-positive cells and the percentage of AVP neurons that also were TRPV4-positive in the SON of BDL rats. In the hypothalamus of BDL rats, TRPV4 lipid raft association increased compared with sham (from 100% ± 2.1 to 326.1% ± 16). This effect was significantly attenuated in BDL rats given 2% saline to drink (174% ± 11). In the brain stem, TRPV4 lipid raft association was reduced by BDL and inversely related to plasma AVP and PRA. We speculate that changes in TRPV4 expression and compartmentalization within lipid rafts could contribute to a feed-forward mechanism related to AVP release in cirrhosis.

This study examined the effects of dehydration and rehydration with water on Fos and FosB staining in the brainstem of rats. Male rats were water deprived for 48 h (Dehyd, n = 7) or 46 h followed by 2 h access to water (Rehyd, n = 7). Controls had ad libitum access to water (Con, n = 9). Brainstems were stained for Fos and FosB/ΔFosB using commercially available antibodies. In the nucleus of the solitary tract (NTS), the number of Fos stained neurons was significantly increased by dehydration and increased further following rehydration (Con 5 ± 1; Dehyd 22 ± 1; Rehyd 48 ± 5). The average number of Fos-positive cells in the parabrachial nucleus (PBN) was significantly increased only by rehydration (Con 12 ± 2; Dehyd 6 ± 2; Rehyd 51 ± 4). The area postrema (AP) showed significant increases in Fos staining after dehydration and rehydration (Fos: Con 4 ± 1; Dehyd 28 ± 3; Rehyd 24 ± 3). In the rostral ventrolateral medulla (RVL), Fos staining significantly increased after dehydration and this effect was reduced by rehydration (Con 3 ± 1; Dehyd 21 ± 2; Rehyd 12 ± 1). In contrast, Fos staining in the caudal ventrolateral medulla (CVL) was not significantly influenced following either dehydration or rehydration with water (Con 4 ± 1; Dehyd 4 ± 1; Rehyd 5 ± 1). FosB/ΔFosB staining in the NTS, AP, and RVL was comparably increased by dehydration and rehydration. In the PBN and CVL, FosB/ΔFosB staining was not affected by the treatments. Dehydration and rehydration have regionally specific effects on Fos and FosB/ΔFosB staining in the brainstem.

We studied c-Fos staining in adult male rats after 48 h of water deprivation and after 46 h of water deprivation with 2 h of access to water or physiological saline. Controls were allowed ad libitum access to water and physiological saline. For immunocytochemistry, anesthetized rats were perfused with a commercially available antibody for c-Fos. Dehydration significantly increased plasma vasopressin (AVP), osmolality, plasma renin activity (PRA), hematocrit, and sodium concentration and decreased urinary volume. Fos staining was significantly increased in the median preoptic nucleus, organum vasculosum of the lamina terminalis, supraoptic nucleus (SON), and magnocellular and parvocellular paraventricular nucleus (PVN), as well as the area postrema, nucleus of the solitary tract (NTS), and rostral ventrolateral medulla (RVL). Rehydration with water significantly decreased AVP levels and Fos staining in the SON, PVN, and RVL and significantly increased Fos expression in the perinuclear zone of the SON, NTS, and parabrachial nucleus. Rehydration with water was associated with decreased urinary sodium concentration and hypotonicity, and hematocrit and PRA were comparable to levels seen after dehydration. After rehydration with saline, plasma osmolality, hematocrit, and PRA were not different from control, but plasma AVP and urinary sodium concentration were increased. In the SON, Fos staining was significantly increased, with a great percentage of the Fos cells also stained for oxytocin compared with water deprivation. Changes in Fos staining were also observed in the NTS, RVL, parabrachial nucleus, and PVN. Rehydration with water or saline produces differential effects on plasma AVP, Fos staining, and sodium concentration.

We investigated the effect of exercise timing on attenuation of postprandial hyper-triglyceridemia (PHTG) in individuals with hypertriglyceridemia (HTG). Subjects were 10 males (TG = 290.1 ± 28.5 mg/dl). Each subject performed a control trial (Ctr), 12-hr premeal exercise trial (12-hr Pre), and 24-hr premeal exercise trial (24-hr Pre). In each trial, subjects had a fat-rich meal. In the exercise trials they jogged on a treadmill at 60% of their [Formula: see text] for 1 hr at a designated time. Blood samples were taken at 0 (immediately before the fat meal), and at 2, 4, 6, 8, and 24 hrs after the meal. The results indicated that plasma TG concentrations in 12-hr Pre were lower than in Ctr and 24-hr Pre (p 2-Ch. These results suggest that exercising 12 hrs prior to a fat-meal intake significantly reduces PHTG response whereas exercising 24 hrs prior to the meal does not attenuate PHTG in hypertriglyceridemic men. The effect of an acute exercise bout on PHTG lowering may be short-lived and diminished by 24 hrs. Key words: high-density lipoprotein cholesterol, triglyceride, lipoprotein lipase, insulin