Oxidative Stress in a Rat Model of Obesity-Induced Hypertension

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 685-686
Author(s):  
Anca D Dobrian ◽  
Michael J Davies ◽  
Suzanne D Schriver ◽  
Thomas J Lauterio ◽  
Russell L Prewitt
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Colorimetric Method ◽  
Systolic Pressure ◽  
Fold Increase ◽  
Kidney Cortex ◽  
Strong Increase ◽  
No Production ◽  
Sprague Dawley ◽  
Enos Expression

45 The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity (Dobrian AD et al Hypertension 2000;35: in press). When Sprague-Dawley rats (n=60) are fed a moderately high fat diet(32kcal% fat) for 10-16 weeks, about half of them develop obesity (obesity-prone (OP) and mild hypertension (153±3.4 mmHg systolic pressure), whereas the other half (obesity-resistant, OR) maintains body weight equivalent to low fat control (C) and are normotensive. We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) are showing a significant increase in the LDL fraction of OP rats (2.8±0.32 nmol MDA/mg protein) compared to OR and C (0.9±0.3 nmol MDA/mg protein). Also, aortic and kidney TBARS showed a significant 3- and 5- fold increase in OP rats after 16 weeks of diet (3.3±0.44 aorta and 6.7±0.52 nmol MDA/mg protein kidney) vs OR. In addition, superoxide generation by aortic rings, measured by lucigenin (25μM) luminescence showed a 2-fold increase in the OP group (4325.6±174 RLU/15 min/mg DNA X10 5 ) compared to both OR and C. Plasma renin activity was 2-fold increased in OP vs both OR and control groups.The urine nitrate/nitrite measured by LDH colorimetric method showed a 1.8-fold decrease in OP rats (2.4±0.17 μmoles) compared to OR. A similar 1.6-fold decrease was found for plasma nitrate/nitrite in OP rats vs OR and C. However, eNOS expression assessed by semiquantitative RT-PCR showed a strong increase in the OP rats vs OR and controls in both kidney cortex(eNOS/β-actin ratio of 0.78±0.21 in OP vs 0.32±0.16 in OR)and medulla(0.86±0.18 in OP vs 0.36±0.14 in OR), suggesting a possible shift toward superoxide vs NO production by the eNOS enzyme.Also, eNOS expression was increased ∼4.8-fold in the thoracic aorta of OP compared to OR rats. Collectively, data show a decreased NO production in OP animals, due in part to the increased oxidative stress, possibly generated by the activation of renin-angiotensin system and increased eNOS expression.

Vitamin E reduces glomerulosclerosis, restores renal neuronal NOS, and suppresses oxidative stress in the 5/6 nephrectomized rat

2007 ◽  
Vol 292 (5) ◽  
pp. F1404-F1410 ◽  
Author(s):  
You-Lin Tain ◽  
Gary Freshour ◽  
Anna Dikalova ◽  
Kathy Griendling ◽  
Chris Baylis
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Vitamin E ◽  
Kidney Cortex ◽  
Antioxidant Vitamin ◽  
No Production ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide

Chronic kidney disease is accompanied by nitric oxide (NO) deficiency and oxidative stress, which contribute to progression. We investigated whether the antioxidant vitamin E could preserve renal function and NO bioavailability and reduce oxidative stress in the 5/6th nephrectomy (NX) rat model. We studied the following three groups of male Sprague-Dawley rats: sham ( n = 6), 5/6 NX control ( n = 6), and 5/6 NX treated with vitamin E (5,000 IU/kg chow; n = 5). The 5/6 NX group showed increased severity of glomerulosclerosis vs. sham, and this was ameliorated by vitamin E therapy. Both 5/6 NX groups showed similar elevations in plasma creatinine and proteinuria and decreased 24-h creatinine clearance compared with sham. There was increased NADPH-dependent superoxide production in 5/6 NX rats vs. sham that was prevented by vitamin E. Total NO production was similarly reduced in both 5/6 NX groups. There was unchanged abundance of endothelial nitric oxide synthesis (NOS) in renal cortex and medulla and neuronal (n) NOS in medulla. However, in kidney cortex, 5/6 NX rats had lower nNOS abundance than sham, which was restored by vitamin E. An increased plasma asymmetric dimethylarginine occurred with 5/6 NX associated with decreased renal dimethylarginine dimethylaminohydrolase activity and increased type 1 protein arginine methyltransferase expression.

scholarly journals rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Wan-cheng Yu ◽  
Hai-ying Chen ◽  
Hong-li Yang ◽  
Peng Xia ◽  
Cheng-wei Zou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Signal Transduction ◽  
Rat Model ◽  
Systolic Pressure ◽  
Negative Control ◽  
No Production ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Hemodynamic ◽  
And Oxidative Stress

Background/Objectives. Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3η signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 (Cav-1F92A) gene may enhance NO production. This study explored the effect of Cav-1F92A-modified rat bone marrow mesenchymal stem cells (rBMSC/Cav-1F92A) on oxidative stress regulation through CA1/kininogen and SelW/14-3-3η signal transduction in a rat model of monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Method. PAH was induced in rats through the subcutaneous injection of MCT. Next, rBMSC/Vector (negative control), rBMSC/Cav-1, rBMSC/Cav-1F92A, or rBMSC/Cav-1F92A+L-NAME were administered to the rats. Changes in pulmonary hemodynamic and vascular morphometry and oxidative stress levels were evaluated. CA1/kininogen and SelW/14-3-3η signal transduction, endothelial nitric oxide synthase (eNOS) dimerization, and eNOS/NO/sGC/cGMP pathway changes were determined through real-time polymerase chain reaction, Western blot, or immunohistochemical analyses. Results. In MCT-induced PAH rats, rBMSC/Cav-1F92A treatment reduced right ventricular systolic pressure, vascular stenosis, and oxidative stress; downregulated CA1/kininogen signal transduction; upregulated SelW/14-3-3η signal transduction; and reactivated the NO pathway. Conclusions. In a rat model of MCT-induced PAH, rBMSC/Cav-1F92A reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3η signal transduction.

Abstract 15949: High Intensity Interval Training is Superior to Continuous Training and Reverses RV Remodeling and Dysfunction in a Rat Model of Pulmonary Hypertension

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Mary Beth Brown ◽  
Evandro Neves ◽  
Rachel Novack ◽  
Amanda Fisher ◽  
Robert Presson ◽  
...  
Keyword(s):  
Rat Model ◽  
High Intensity ◽  
Systolic Pressure ◽  
Interval Training ◽  
Wall Stress ◽  
High Intensity Interval Training ◽  
Sprague Dawley ◽  
Continuous Training ◽  
Sheer Stress ◽  
High Intensity Interval

Exercise appears to have overall benefit in pulmonary arterial hypertension (PAH); however, studies to date indicate little effect on the elevated pulmonary pressure or RV hypertrophy (RVH) and dysfunction associated with the disease. High intensity interval training (HIIT) is reported to be superior to the more customary prolonged continuous exercise training (CExT) protocol for chronic heart failure but has not been tested for PAH. Therefore, we investigated impact of a 6 wk HIIT vs. CExT treadmill program in a monocrotaline rat model of mild PAH (MCT, 40 mg/kg) on indicators of disease progression. Methods: Treadmill training was performed 5x/wk in male Sprague-Dawley MCT rats (250-300g), following a protocol of either HIIT (5 cycles of 2 min at ~90% VO 2 reserve [VO 2 R] + 3 min at 30% VO 2 R; n=8), or low intensity CExT (60 min at 50% VO 2 R; n=7). Statistical analysis was performed by one-way ANOVA. Results: MCT-induced decrements in VO 2 max were ameliorated by both HIIT and CExT (p < 0.01 vs. sedentary MCT rats, MCT-SED, n=6), and were similar to healthy controls (CON, n=6). Most importantly, RV systolic pressure (RVSP, in mmHg; via Millar catheter) and RVH (ratio of RV to LV+S mass) were lowered (p<0.05) only by HIIT (28.7±2, and 0.32±0.02) and not by CExT (44.1±3, and 0.43±0.01) vs. MCT-SED (40.2±3.2, and 0.41±0.02). Cardiac output (Δ from baseline in μl, via RV echocardiography) was also improved by HIIT (117±28) vs. MCT-SED (6±42, p=0.04). Additional hemodynamic recordings during running, via novel implantable telemetry (DSI), were obtained serially at pre- and 2, 4, 6, and 8 wks post-MCT, and revealed ‘surges’ in RVSP during HIIT, vs. a steady RVSP pattern during CExT. Pulmonary eNOS (per immunoblotting) was increased (p<0.05) with HIIT, consistent with greater endothelial stimulation. Conclusions: HIIT is superior to CExT for improving hemodynamics and RV remodeling and dysfunction in MCT rats and warrants further investigation in other models and in patients. More favorable outcomes may be explained by greater sheer-stress mediated vascular endothelial adaptation to HIIT stimulus, or lower cumulative training-induced RV wall stress with the briefer HIIT session duration.

scholarly journals The Customizable E-cigarette Resistance Influences Toxicological Outcomes: Lung Degeneration, Inflammation, and Oxidative Stress-Induced in a Rat Model

2019 ◽  
Vol 172 (1) ◽  
pp. 132-145 ◽  
Author(s):  
Silvia Cirillo ◽  
Fabio Vivarelli ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
Sabrina Burattini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Low Voltage ◽  
Pulmonary Inflammation ◽  
Bronchial Epithelium ◽  
Sprague Dawley ◽  
Public Health Agencies ◽  
Toxicological Effects ◽  
Inflammatory Status ◽  
Sprague Dawley Rats

Abstract Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.

scholarly journals Seoritae Extract Reduces Prostate Weight and Suppresses Prostate Cell Proliferation in a Rat Model of Benign Prostate Hyperplasia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hoon Jang ◽  
Woong-Jin Bae ◽  
Seung-Mo Yuk ◽  
Dong-Seok Han ◽  
U-Syn Ha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Reductase Activity ◽  
Sprague Dawley ◽  
Prostate Hyperplasia ◽  
Prostate Cell ◽  
Beneficial Effects ◽  
Prostate Weight ◽  
Sprague Dawley Rats ◽  
Health Promoting

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.

scholarly journals Pregnant rats treated with a high-fat/prooxidant Western diet with ANG II and TNF-α are resistant to elevations in blood pressure and renal oxidative stress

2015 ◽  
Vol 308 (11) ◽  
pp. R945-R956 ◽  
Author(s):  
Mark W. Cunningham ◽  
Crystal A. West ◽  
Xuerong Wen ◽  
Aihua Deng ◽  
Chris Baylis
Keyword(s):  
Oxidative Stress ◽  
Western Diet ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Sprague Dawley ◽  
High Fat ◽  
Redox Systems ◽  
Plasma Protein Concentration ◽  
Pregnant Rats ◽  
Tnf Α

Oxidative stress and inflammation are risk factors for hypertension in pregnancy. Here, we examined the 24-h mean arterial pressure (MAP) via telemetry and the nitric oxide (NO) and redox systems in the kidney cortex, medulla, and aorta of virgin and pregnant rats treated with a high-fat/prooxidant Western diet (HFD), ANG II, and TNF-α. Female Sprague-Dawley rats were given a normal diet (ND) or a HFD for 8 wk before mating. Day 6 of pregnancy and age-matched virgins were implanted with minipumps infusing saline or ANG II (150 ng·kg−1·min−1) + TNF-α (75 ng/day) for 14 days. Groups consisted of Virgin + ND + Saline (V+ND) ( n = 7), Virgin + HFD +ANG II and TNF-α (V+HFD) ( n = 7), Pregnant + ND + Saline (P+ND) ( n = 6), and Pregnant + HFD + ANG II and TNF-α (P+HFD) ( n = 8). After day 6 of minipump implantation, V+HFD rats displayed an increase in MAP on days 7, 8, and 10–15 vs. V+ND rats. P+HFD rats, after day 6 of minipump implantation, showed an increase in MAP only on day 7 vs. P+ND rats. P+HFD rats had a normal fall in 24-h MAP, hematocrit, plasma protein concentration, and osmolality at late pregnancy. No change in kidney cortex, medulla, or aortic oxidative stress in P+HFD rats. P+HFD rats displayed a decrease in nNOSβ abundance, but no change in kidney cortex NOxcontent vs. P+ND rats. Pregnant rats subjected to a chronic HFD and prooxidant and proinflammatory insults have a blunted increase in 24-h MAP and renal oxidative stress. Our data suggest renal NO bioavailability is not altered in pregnant rats treated with a HFD, ANG II, and TNF-α.

scholarly journals Carvedilol Exerts Neuroprotective Effect on Rat Model of Diabetic Neuropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Rania M. Magadmi ◽  
Mujahid A. Alsulaimani ◽  
Aziza R. Al-Rafiah ◽  
Muhammad Saeed Ahmad ◽  
Ahmed Esmat
Keyword(s):  
Oxidative Stress ◽  
Diabetic Neuropathy ◽  
Rat Model ◽  
Histopathological Examination ◽  
Neuroprotective Effect ◽  
Negative Control ◽  
Diabetic Patients ◽  
Sprague Dawley ◽  
Behavioural Tests ◽  
Diabetes Induction

Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. This study aimed to investigate the potential neuroprotective effect of carvedilol on STZ-induced DN in rats. Thirty male Sprague Dawley rats (weighing 200–250 g) were randomly divided into five groups (six/group), where group 1 (negative control) received only the vehicle (0.5% of carboxymethyl cellulose orally 1 ml/kg). DN was induced by a single injection of remaining rats with streptozotocin (STZ; 50 mg/kg, i.p.). After diabetes induction, group 2 served as the diabetic untreated animals; while groups 3 and 4 were treated with carvedilol (1 and 10 mg/kg/d, orally, respectively). Group 5 received a-lipoic acid as a reference neuroprotective (100 mg/kg/d, orally). All treatments were continued for 45 days after diabetes induction, followed by behavioural tests. After sacrificing the animals, dorsal root ganglia, and sciatic nerves were collected for histopathological examination and biochemical assessments. Briefly, STZ administration caused cold allodynia, induced oxidative stress, and increased nerve growth factor (NGF) concentration. Nevertheless, carvedilol improved the behavioural tests, ameliorated the oxidative imbalance as manifested by reducing malondialdehyde, restoring glutathione content, and superoxide dismutase activity. Carvedilol also decreased NGF concentration in DRG homogenate. In conclusion, this study demonstrates the neuroprotective effect of carvedilol in an experimentally induced DN rat model through–at least partly–its antioxidant effect and reduced NGF concentration in DRG.

Abstract P269: Circulating Factors in Response to Placental Ischemia Cause Vascular Endothelial Mitochondrial Oxidative Stress

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Venkata Ramana Vaka ◽  
Kristen M McMaster ◽  
Mark W Cunningham ◽  
Tarek Ibrahim ◽  
Lorena M Amaral ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Fold Increase ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Mitochondrial Oxidative Stress ◽  
Respiration Rates ◽  
Sprague Dawley Rats ◽  
Placental Ischemia ◽  
New Onset

Introduction: Preeclampsia (PE) is associated with placental ischemia, new onset hypertension, oxidative stress and endothelial dysfunction. Factors linking placental ischemia with endothelial dysfunction and hypertension are not completely understood. Mitochondrial (mt) dysfunction (dys) is a major source of reactive oxygen species (ROS) and we have shown that placental ischemia causes oxidative stress in RUPP rats. We hypothesize that circulating factors in RUPP rats cause vascular endothelial mt dys and mt ROS as a contributor to endothelial dysfunction and hypertension during pregnancy. Methods: Female Sprague Dawley rats were dived into two groups; normal pregnant (NP) and RUPP rats. On gestational day (GD) 14, RUPP surgery was performed, GD18 carotid catheters were inserted, and GD19 conscious blood pressure (MAP) was measured. GD 19 placentas were collected and mitochondria were isolated for respiration and ROS measurements. Mt ROS was measured spectrophotometrically in HUVECs incubated with 10% serum from NP or RUPP rats using MitoSox Red. Results: MAP was elevated in RUPP (n=9) compared to NP rats (n=9) (122±2 vs. 104±2 mmHg, p<0.05). State 3 (313±16 vs 423±15 pmol/sec/mg, p<0.05) and maximal (244±13 vs 300±11 pmol/sec/mg, p<0.05) respiration rates were significantly reduced in placental mitochondria from RUPP (n=7) vs NP (n=8) rats. RUPP placental mitochondria show 35-fold increase in ROS production compared NP mitochondria (p<0.05). HUVECs incubated with RUPP (n=7) serum showed significantly increased ROS vs NP (n=7) serum (9±3 vs 3±1, % gated, p=0.05). Conclusion: Reduced placental mitochondrial respiration and increased mt ROS support the hypothesis that mt dys and mt ROS occurs in response to placental ischemia. Importantly, increased ROS from endothelial cells in response to RUPP serum indicate the importance of circulating factors to cause vascular mt dyst and mt ROS.

scholarly journals Serelaxin reduces oxidative stress and asymmetric dimethylarginine in angiotensin II-induced hypertension

2014 ◽  
Vol 307 (12) ◽  
pp. F1355-F1362 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Mark W. Cunningham ◽  
Chris Baylis
Keyword(s):  
Oxidative Stress ◽  
Asymmetric Dimethylarginine ◽  
Oxidation Products ◽  
No Oxidation ◽  
Kidney Cortex ◽  
High Dose ◽  
Protective Effects ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Induced Hypertension

Recent findings suggest the therapeutic action of relaxin during hypertension is dependent on nitric oxide synthase (NOS) activation; however, the mechanisms underlying the beneficial effects of relaxin on the NOS system have not been fully elucidated. We hypothesized that the protective effects of relaxin include reducing both oxidative stress and the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). We examined the effect of Serelaxin [human recombinant relaxin-2 (RLX)] in male Sprague-Dawley rats given high-dose angiotensin (ANG) II (400 ng·kg−1·min−1 sc) for 6 wk or shams. RLX was administered (4 μg/h sc) to half of the rats in each group after 2 wk of ANG II for the remaining 4 wk. ANG II induced hypertension and proteinuria, reduced NO oxidation products (NOx), and increased oxidative stress (NADPH oxidase activity, thiobarbituric acid-reactive substances, and 8-isoprostane excretion) and plasma ADMA. While RLX had no effect on sham rats, RLX attenuated the ANG II-dependent hypertension (165 ± 5 vs. 135 ± 13 mmHg, P < 0.05) and proteinuria at 6 wk (62 ± 6 vs. 41 ± 4 mg·day−1·100 g−1, P < 0.05) and normalized oxidative stress and circulating ADMA, in association with restored NOx excretion and kidney cortex NOx. We found that RLX had no impact on the ADMA-regulatory enzymes protein arginine methyltransferase and dimethylarginine-dimethylaminohydrolase (DDAH). Furthermore, RLX treatment did not increase DDAH activity in kidney cortex or liver. These data suggest that benefits of RLX treatment include reduced ADMA levels and increased NO bioavailability, possibly due to its antioxidant effects.

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