Effect of vitamin C and E on oxidative stress and antioxidant system in the salivary glands of STZ-induced diabetic rats.

OBJECTIVE: We examined the effects of vitamin C and E supplementation in the prevention of oxidative stress in the salivary glands of STZ-induced diabetic rats. DESIGN: Forty-eight male Wistar rats were divided into six groups (n = 8 in each): control (C), control supplemented with vitamin C (Cvc) and E (Cve), diabetic (D), and diabetic supplemented with vitamin C (Dvc) and E (Dve). Vitamin C (150 mg/kg) and E (300 mg/kg) were daily administered for 21 days. Serum ascorbic acid and α-tocopherol levels were quantified. Glandular levels of hydrogen peroxide (H2O2), superoxide anion (O2-), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), malondialdehyde (MDA) and the total antioxidant status (TAS) were estimated. RESULTS: Vitamin C and E levels were reduced in D group. Vitamin C decreased the levels of O2- in the salivary gland of diabetic rats. Vitamin E increased the concentration of O2- in PA gland of diabetic animals. In the SM gland of the diabetic group, MDA, SOD, GPx and TAS increased. Dve presented reduced SOD activity and increased GR, GPx, and MDA. Dve increased GPx, Gr and TAS levels. In the PA gland, MDA, SOD, CAT, GPx, GR, and TAS were similar in C and D. TAS, SOD, CAT, GPx, and GR increased in Dvc. Vitamin E supplementation resulted in increased MDA and CAT levels and reduced SOD activity. CONCLUSION: In the SM glands of the diabetic rats, vitamin C supplementation improved the antioxidant system, while vitamin E acted as pro-oxidant.

Melatonin attenuates renal sympathetic overactivity and reactive oxygen species in the brain in neurogenic hypertension.

Sympathetic overactivation contributes to the pathogenesis of both experimental and human hypertension. We have previously reported that oxidative stress in sympathetic premotor neurons leads to arterial baroreflex dysfunction and increased sympathetic drive to the kidneys in an experimental model of neurogenic hypertension. In this study, we hypothesized that melatonin, a potent antioxidant, may be protective in the brainstem regions involved in the tonic and reflex control of blood pressure (BP) in renovascular hypertensive rats. Neurogenic hypertension was induced by placing a silver clip (gap of 0.2 mm) around the left renal artery, and after 5 weeks of renal clip placement, the rats were treated orally with melatonin (30 mg/kg/day) by gavage for 15 days. At the end of melatonin treatment, we evaluated baseline mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), and the baroreflex control of heart rate (HR) and rSNA. Reactive oxygen species (ROS) were detected within the brainstem regions by dihydroethidium staining. Melatonin treatment effectively reduced baseline MAP and sympathoexcitation to the ischemic kidney in renovascular hypertensive rats. The baroreflex control of HR and rSNA were improved after melatonin treatment in the hypertensive group. Moreover, there was a preferential decrease in ROS within the rostral ventrolateral medulla (RVLM) and the nucleus of the solitary tract (NTS). Therefore, our study indicates that melatonin is effective in reducing renal sympathetic overactivity associated with decreased ROS in brainstem regions that regulate BP in an experimental model of neurogenic hypertension.

The antioxidant effects of green tea reduces blood pressure and sympathoexcitation in an experimental model of hypertension.

BACKGROUND: Oxidative stress is a key mediator in the maintenance of sympathoexcitation and hypertension in human and experimental models. Green tea is widely known to be potent antioxidant. OBJECTIVE: We aimed to evaluate the effects of green tea in a model of hypertension. METHODS: Hypertension was induced by the nitric oxide synthase inhibitor [N-nitro-L-arginine-methyl-ester (L-NAME); 20 mg/kg per day, orally, for 2 weeks] in male Wistar rats. After the first week of L-NAME treatment, animals received green tea ad libitum for 1 week. At the end of the treatment period, blood pressure, heart rate, baroreflex sensitivity, renal sympathetic nerve activity, and vascular and systemic oxidative stress were assessed. RESULTS: L-NAME-treated animals exhibited an increase in blood pressure (165 ±â€Š2 mmHg) compared with control rats (103 ±â€Š1 mmHg) and green tea treatment reduced hypertension (119 ±â€Š1 mmHg). Hypertensive animals showed a higher renal sympathetic nerve activity (161 ±â€Š12 spikes/s) than the control group (97 ±â€Š2 spikes/s), and green tea also decreased this parameter in the hypertensive treated group (125 ±â€Š5 spikes/s). Arterial baroreceptor function and vascular and systemic oxidative stress were improved in hypertensive rats after green tea treatment. CONCLUSIONS: Taken together, short-term green tea treatment improved cardiovascular function in a hypertension model characterized by sympathoexcitation, which may be because of its antioxidant properties.

Chronic sleep restriction during pregnancy--repercussion on cardiovascular and renal functioning of male offspring.

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi - tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127 ± 2.6 (19); OCSR: 144 ± 2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: -2.6 ± 0.15 (9); OCRS: -1.6 ± 0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4 ± 15 (18); OSR: 60.2 ± 3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4 ± 0.2 (10); OCSR: 7.4 ± 0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring.

P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and architecture.

Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1ß, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.

Electroacupuncture and moxibustion decrease renal sympathetic nerve activity and retard progression of renal disease in rats.

BACKGROUND/AIM: Chronic kidney disease (CKD) is an increasing major public health problem worldwide. The sympathetic nervous system and nitric oxide play an important role in the pathogenesis of CKD. Traditional Chinese medicine has accumulated thousands of years of therapeutic experiences. Electroacupuncture (EA) and moxibustion (MO) are two such therapeutic strategies. The aim of this study was to investigate the renal and hemodynamic effects of EA-MO in an experimental model of a CKD. METHODS: Male Wistar rats submitted to 5/6th nephrectomy (5/6 NX) were studied for 8 weeks. There were four groups: (1) control, normal rats; (2) NX, 5/6 NX only; (3) NX-AS, 5/6 NX and EA-MO session using sham points, and (4) NX-AM, 5/6 NX and EA-MO session using real acupoints. Biochemical and blood pressure studies, renal sympathetic nerve activity measurements, nitric oxide levels and the histopathological indices were assessed. RESULTS: The EA- and MO-treated group presented significant improvement in all measured functional and histopathological parameters. CONCLUSION: These findings suggest that EA-MO had beneficial effects on CKD. This effect was probably achieved by the modulation of the renal sympathetic nerve activity and nitric oxide levels, leading to decreased blood pressure, which is associated with less proteinuria.