Function In Sprague-Dawley Rats Research Articles

Molecular disturbances and thyroid gland dysfunction in rats chronically exposed to a high dose of NaAsO₂: Insights from proteomic and phosphoproteomic analyses

Arsenic is a ubiquitous hazardous metalloid that poses a significant threat to human health. Although researchers have investigated the detrimental effects of arsenic on the thyroid, a comprehensive exploration of its toxicological impact and underlying molecular mechanisms remains to be conducted. Both this study and our previous reports demonstrated that chronic exposure to sodium arsenite (NaAsO2) results in histological impairment and dysfunction of the thyroid glands in Sprague-Dawley (SD) rats. Proteomic and phosphoproteomic analyses were performed to investigate the molecular mechanisms underlying the effects of chronic NaAsO2 exposure on thyroid function in SD rats. NaAsO2 disrupts the synthesis of thyroid hormones (THs) and alters the expression of the THs-synthesizing enzyme dual oxidase 2. In addition, oxidative phosphorylation, the AMP-activated protein kinase signaling pathway, central carbon metabolism in cancer, cysteine and methionine metabolism, cellular response to heat stress, and protein processing in the endoplasmic reticulum were upregulated, whereas glutathione metabolism was downregulated. In conclusion, this study revealed thyroid damage in SD rats induced by chronic NaAsO2 exposure and elucidated the disrupted molecular pathways, thereby providing novel insights into the molecular mechanisms underlying arsenic exposure and its impact on thyroid function.

Effects of voluntarily consumed sweetened alcohol and naringin on cardiac function in male and female Sprague-Dawley rats.

This study assessed the impact of sweetened alcohol and naringin on cardiac function in Sprague-Dawley rats. Male (n = 40) and female (n = 40) rats were allocated to control, sweetened alcohol (SOH), naringin (NA), and sweetened alcohol with naringin (SOH + NA) groups. SOH and SOH + NA rats received 10% alcohol + 20% fructose in gelatine; SOH + NA and NA rats received 50 mg/kg naringin in gelatine daily for 10 weeks. Echocardiography was performed to assess left ventricular (LV) function. LV cardiomyocyte diameters and collagen area fraction were determined by H&E and picrosirius-red staining, respectively. In males, sweetened alcohol and naringin did not affect cardiac function. Female SOH rats had increased LV end-diastolic posterior wall (p = 0.04), relative wall thicknesses (p = 0.01), and LV cardiomyocyte diameters (p = 0.005) compared with control. Female SOH and SOH + NA had reduced lateral e' and e'/a' and increased E/e' (p < 0.0001). Female SOH (p = 0.01) and SOH + NA (p = 0.04) rats had increased LV collagen area fraction compared with controls. In males, neither sweetened alcohol nor naringin affected cardiac geometry or diastolic function. In females, sweetened alcohol induced concentric remodelling, impaired LV relaxation, and elevated filling pressures. Naringin may have the potential to improve the sweetened alcohol-induced concentric remodelling; however, it did not ameliorate diastolic dysfunction in females.

(068) Perfluorooctane Sulfonate (pfos) And Perfluorooctanic Acid (pfoa) Sub-chronic Exposure has Minimal Impact on Erectile Function in Sprague-dawley Ratsa

Abstract Introduction Per and polyfluoroalkyl substances (PFAS) are commonly used in industrial and consumer products and are environmental and health contaminants. The most common PFAS chemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanic acid (PFOA), are used in firefighting foam, nonstick bakeware, water-resistant fabrics, grease-resistant paper and fire-resistant materials. PFAS is a known endocrine disruptor and can reduce testosterone and lower semen quality. The impact of PFAS exposure on erectile physiology is unknown. Objective Our study will assess the effect of PFOS and PFOA on erectile function in Sprague-Dawley rats. We hypothesize that PFOS and PFOA will decrease erectile function. Methods Adult male Sprague-Dawley rats were divided into three groups (n=10/group): 1) Control; 2) PFOS (10mg/kg/day); and 3) PFOA (10mg/kg/day). PFOS/PFOA was dissolved in 0.05% Tween 20 and administered in drinking water for 28 days. Controls received 0.05% Tween 20 in drinking water. The study was carried out in two different cohorts of rats (n=4 and n=6/group). Following 28 days of PFOS/PFOA exposure, rats were placed on regular drinking water for 2 weeks. Body weights were collected weekly and terminal organ weights of liver, testes, spleen, heart, lungs, brain, seminal vesicles, kidneys, bladder, and thymus were recorded. Erectile function was assessed prior to PFAS exposure and every 2 weeks thereafter via apomorphine-induced behavioral erections and yawns. Nerve-stimulated intracavernosal pressure and mean arterial pressure (ICP/MAP) was measured 2 weeks after exposure stopped. Results Four weeks of PFOS exposure significantly decreased body weight while PFOA exposure did not impact body weight (Con: 588±63.5g; PFOS: 453±16.3g; PFOA: 535±29.9g, p&amp;lt;0.01). The PFOS dose in the second cohort was overtly toxic with 5/6 rats dying following 3-4 weeks of exposure. Two weeks following PFOS/PFOA exposure, livers were markedly enlarged (Con: 19.4±2.85g; PFOS: 25.4±0.16g; PFOA: 20.2±3.77g, p&amp;lt;0.01), spleens were smaller (Con: 0.93±0.12g; PFOS: 0.65±0.03g; PFOA: 0.88±0.12g, p&amp;lt;0.05), and testes were larger in PFOS rats (Con: 1.8±0.07g; PFOS: 2.0±0.06g; PFOA: 1.8±0.07). No other organ weights were different across exposure groups. PFOS/PFOA exposed animals had similar numbers of apomorphine-induced erections throughout the 6 week period. Two weeks post-exposure, ICP/MAP was unchanged between all groups (n=5-10/group). Ongoing studies will assess testosterone levels. Conclusions A sub-chronic PFOS exposure markedly decreased body weight, increased liver size, decreased spleen weight, and increased testes weight. PFOA exposure did not impact body or organ weights. Following PFOS or PFOA exposure, there was no change in apomorphine-induced behavioral erections or ICP/MAP. Additionally, the dose of PFOS assessed was quite toxic to the second cohort of animals. Future studies will assess if a more chronic exposure will impact erectile function. Disclosure No.

Effects of Light-To-Moderate Chinese Baijiu Consumption on Serum Lipid Metabolism and Liver Function of Sprague-Dawley Rats

We have investigated the effect of light-to-moderate baijiu consumption on serum lipid metabolism and liver function in vivo. To this end, six groups of rats received increasing dosage of baijiu (0.5–5.0 mL/kg) for 8 weeks and multiple markers of lipid metabolism and liver function were evaluated. Compared to that of the blank control, at the baijiu dosage of 3.0 mL/kg, the levels of high-density lipoprotein cholesterol, reduced glutathione, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity increased significantly (P &lt; 0.05), whereas malondialdehyde level decreased (P &lt; 0.05). In comparison to the pure ethanol groups, with baijiu groups at the same level of alcohol revealed that baijiu had noticeably positive impact in ameliorating the changes in the values of all parameters examined. In summary, regular consumption of light-to-moderate amount of baijiu may significantly enhance the metabolism of serum lipids and enhance liver function.

Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.

We previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide) to activate CB1 receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms supporting paracetamol-induced analgesia remain unknown. The effects of paracetamol on brain function in Sprague-Dawley rats were determined by functional MRI. Levels of neurotransmitters in the periaqueductal grey (PAG) were measured using in vivo 1 H-NMR and microdialysis. Analgesic effects of paracetamol were assessed by behavioural tests and challenged with different inhibitors, administered systemically or microinjected in the PAG. Paracetamol decreased the connectivity of major brain structures involved in pain processing (insula, somatosensory cortex, amygdala, hypothalamus, and the PAG). This effect was particularly prominent in the PAG, where paracetamol, after conversion to AM404, (a) modulated neuronal activity and functional connectivity, (b) promoted GABA and glutamate release, and (c) activated a TRPV1 channel-mGlu5 receptor-PLC-DAGL-CB1 receptor signalling cascade to exert its analgesic effects. The elucidation of the mechanism of action of paracetamol as an analgesic paves the way for pharmacological innovations to improve the pharmacopoeia of analgesic agents.

WITHDRAWN: Gestational and lactational exposure to atrazine affects behavior and cognitive functions in Sprague-Dawley rats

WITHDRAWN: Gestational and lactational exposure to atrazine affects behavior and cognitive functions in Sprague-Dawley rats

Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague-Dawley rats.

What is the central question of this study? Does crosstalk exist between leptin and interleukin-6 in colonic enteric neurons, and is this a contributory factor in gastrointestinal dysfunction associated with irritable bowel syndrome? What is the main finding and its importance? Leptin ameliorates the prosecretory and prokinetic effects of the pro-inflammatory cytokine interleukin-6 on rat colon. Leptin also suppresses the neurostimulatory effects of irritable bowel syndrome plasma, which has elevated concentrations of interleukin-6, on enteric neurons. This may indicate a regulatory role for leptin in immune-mediated bowel dysfunction. In addition to its role in regulating energy homeostasis, the adipokine leptin modifies gastrointestinal (GI) function. Indeed, leptin-resistant obese humans and leptin-deficient obese mice exhibit altered GI motility. In the functional GI disorder irritable bowel syndrome (IBS), circulating leptin concentrations are reported to differ from those of healthy control subjects. Additionally, IBS patients display altered cytokine profiles, including elevated circulating concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6), which bears structural homology and similarities in intracellular signalling to leptin. This study aimed to investigate interactions between leptin and IL-6 in colonic neurons and their possible contribution to IBS pathophysiology. The functional effects of leptin and IL-6 on colonic contractility and absorptosecretory function were assessed in organ baths and Ussing chambers in Sprague-Dawley rat colon. Calcium imaging and immunohistochemical techniques were used to investigate the neural regulation of GI function by these signalling molecules. Our findings provide a neuromodulatory role for leptin in submucosal neurons, where it inhibited the stimulatory effects of IL-6. Functionally, this translated to suppression of IL-6-evoked potentiation of veratridine-induced secretory currents. Leptin also attenuated IL-6-induced colonic contractions, although it had little direct effect on myenteric neurons. Calcium responses evoked by IBS plasma in both myenteric and submucosal neurons were also suppressed by leptin, possibly through interactions with IL-6, which is elevated in IBS plasma. As leptin has the capacity to ameliorate the neurostimulatory effects of soluble mediators in IBS plasma and modulated IL-6-evoked changes in bowel function, leptin may have a role in immune-mediated bowel dysfunction in IBS patients.

Effect of aging on brain volume and cognitive function in Sprague-Dawley rats

Event Abstract Back to Event Effect of aging on brain volume and cognitive function in Sprague-Dawley rats Hamizah S. Hamezah1, 2, Lina W. Durani1, 2, Nor F. Ibrahim1, 2, Daijiro Yanagisawa1, Tomoko Kato1, Akihiko Shiino1, Hanafi A. Damanhuri2, Wan Z. Wan Ngah2 and Ikuo Tooyama1* 1 Shiga University of Medical Science, Molecular Neuroscience Research Center, Japan 2 Universiti Kebangsaan Malaysia, Department of Biochemistry, Faculty of Medicine, UKMMC, Malaysia Aging is associated with impairments in cognitive functions and locomotor activity, as well as alterations in the brain volume. Therefore, knowing the time of onset at which these alterations occur during aging may help us understanding mechanisms leading to the aging brain. This study was conducted to determine cognitive and brain volume changes of middle to late aged stages of aging in animal model. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27 months old. 1H MRI was performed on the rats, using a 7.0-Tesla MR scanner system. Images of medial prefrontal cortex (mPFC), hippocampus, striatum, lateral ventricle, and cerebellum were analyzed using ImageJ software. Open field, object recognition, and Morris water maze were conducted after MRI measurement to assess locomotor and cognitive functions. The volume of mPFC, hippocampus, striatum, lateral ventricle, and cerebellum were then measured. Our results showed that the specific brain volume did not significantly change with age. Open field test indicated significant decline in the number of line crossing and central entries in 27 months old rats compared with 14 months, which represented locomotor activity deficits at the late-aged rats. Furthermore, impairments in memory of the 27 months old rats were also shown by the significantly lower recognition index to the displaced objects compared with 14 months. Morris water maze results showed that 27 months old rats took significantly longer time and distance to reach the hidden platform compared with 14 months. Probe test indicated significantly lower number of platform crossings in the 27 months old rats compared with 14 months. In conclusion, age-related locomotor and cognitive deficits occur during aging, with most marked impairments observed at late-aged stage. However, no brain volume changes observed across the different ages groups. Keywords: Aging, in vivo, Cognitive Function, magnetic resonance imaging (MRI), brain volume Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Hamezah HS, Durani LW, Ibrahim NF, Yanagisawa D, Kato T, Shiino A, Damanhuri HA, Wan Ngah WZ and Tooyama I (2016). Effect of aging on brain volume and cognitive function in Sprague-Dawley rats. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00140 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Ikuo Tooyama, Shiga University of Medical Science, Molecular Neuroscience Research Center, Otsu, Shiga, Japan, kinchan@belle.shiga-med.ac.jp Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hamizah S Hamezah Lina W Durani Nor F Ibrahim Daijiro Yanagisawa Tomoko Kato Akihiko Shiino Hanafi A Damanhuri Wan Z Wan Ngah Ikuo Tooyama Google Hamizah S Hamezah Lina W Durani Nor F Ibrahim Daijiro Yanagisawa Tomoko Kato Akihiko Shiino Hanafi A Damanhuri Wan Z Wan Ngah Ikuo Tooyama Google Scholar Hamizah S Hamezah Lina W Durani Nor F Ibrahim Daijiro Yanagisawa Tomoko Kato Akihiko Shiino Hanafi A Damanhuri Wan Z Wan Ngah Ikuo Tooyama PubMed Hamizah S Hamezah Lina W Durani Nor F Ibrahim Daijiro Yanagisawa Tomoko Kato Akihiko Shiino Hanafi A Damanhuri Wan Z Wan Ngah Ikuo Tooyama Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effects of naloxone and bicuculline on acquisition of passive avoidance task in mitragynine-treated rats

Event Abstract Back to Event Effects of naloxone and bicuculline on acquisition of passive avoidance task in mitragynine-treated rats Farah W. Suhaimi1*, Zurina Hassan1, Visweswaran Navaratnam1, Christian P. Muller2 and Sharif M. Mansor1 1 Universiti Sains Malaysia, Centre for Drug Research, Malaysia 2 Friedrich-Alexander-University Erlangen-Nuremberg, Department of Psychiatry and Psychotherapy, Germany Mitragynine is the psychoactive substance of Mitragyna speciosa Korth (Kratom), an indigenous plant of the Southeast Asian countries. This plant has been traditionally used as a substitute in the self-treatment of opiate addiction, to reduce pain sensitivity as well as to enhance physical endurance. However, reports on Kratom in various countries have suggested considerable abuse potential despite little understanding on health consequences. We previously reported that acute and chronic administrations of mitragynine impaired learning and memory functions in Sprague-Dawley rats. Pharmacological manipulations of the neural systems that modulate the memory processes may elucidate the possible underlying mechanisms of how mitragynine affects the learning and memory functions. Thus, the present study aims to investigate the involvement of the opioidergic and GABAergic systems in mediating the effects of mitragynine on learning and memory functions. Male Sprague-Dawley rats were co-administered with mitragynine (1, 5, or 10 mg/kg) and naloxone, an opioid antagonist (1.0 mg/kg) or bicuculline, a GABAA antagonist (0.125 mg/kg), immediately after training of the passive avoidance task. Both naloxone and bicuculline were able to overcome the effects of mitragynine on memory retrieval as shown by the increased step-through latencies. Taken together, these results suggest the participations of the opioidergic and GABAergic systems in modulating the effects of mitragynine in learning and memory functions. Acknowledgements Higher Education Centre of Excellence (HICoE) special funding (304.CDADAH.650527.K134) and International Research Collaboration Fund (IReC) (1002.CDADAH.910410) Keywords: Learning, Memory, in vivo, GABAergic system, Psychoactive substance Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Suhaimi FW, Hassan Z, Navaratnam V, Muller CP and Mansor SM (2016). Effects of naloxone and bicuculline on acquisition of passive avoidance task in mitragynine-treated rats. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00118 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Farah W Suhaimi, Universiti Sains Malaysia, Centre for Drug Research, Minden, Penang, Malaysia, sfarahwahida@usm.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Farah W Suhaimi Zurina Hassan Visweswaran Navaratnam Christian P Muller Sharif M Mansor Google Farah W Suhaimi Zurina Hassan Visweswaran Navaratnam Christian P Muller Sharif M Mansor Google Scholar Farah W Suhaimi Zurina Hassan Visweswaran Navaratnam Christian P Muller Sharif M Mansor PubMed Farah W Suhaimi Zurina Hassan Visweswaran Navaratnam Christian P Muller Sharif M Mansor Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The Severity of Ischemia Varies in Sprague-Dawley Rats from Different Vendors

The purpose of this study was to compare acute cerebral perfusion measured by computed tomography, stroke lesion volume measured by magnetic resonance imaging, and motor function in Sprague-Dawley rats supplied by Charles River (Charles River, Quebec, Canada) and Harlan (Harlan, Michigan, USA). During the acute stages of ischemia (&lt;3 hours), Sprague-Dawley rats supplied by Harlan had a greater reduction in blood flow (67%) than rats supplied by Charles River (37%). MRI at days 1 and 6 after ischemia showed larger lesions in the Charles River animals compared to Harlan animals (P&lt;0.05) at both time points. Lesion volume decreased in both Charles River and Harlan rats at day 6 compared to day 1 (P&lt;0.05) and corresponded to lesion size on histology. The Harlan animals had significant functional deficits (P&lt;0.05) one day after surgery in postural hang reflex, forelimb placement, and tactile fraction first tests, whereas rats supplied by Charles River had no significant functional impairment as a result of surgery. The current study provides evidence that differences in response to ischemia between rats of the same strain supplied by different vendors should be an important consideration when animals are selected for the study of cerebral ischemia.

Changes in Serum Electrolytes, Urea, and Creatinine in Aloe Vera-treated Rats

This study was carried out to investigate the effect of Aloe vera extract (AvE) on serum electrolytes, urea, and creatinine as indices of renal function in Sprague-Dawley rats. Twelve male Sprague-Dawley rats weighing between 80 and 130 g were used. Rats were divided into two groups: The control and the test groups (n=6). The test group received 1 ml of AvE daily for 28 days. Both the groups fed on standard rat chow and water ad libitum. The results showed a decrease in serum levels of sodium, and potassium, but an increase in the serum levels of bicarbonate, urea, and creatinine in the test group. The changes seen were, however, statistically insignificant, except for the serum levels of sodium and creatinine (P<0.05). It is thus concluded that AvE impairs renal handling of electrolytes with consequent hyponatremia and hypercreatinemia. However, this might be of therapeutic value in conditions associated with hypernatremia.

Combination therapy with losartan and pioglitazone additively reduces renal oxidative and nitrative stress induced by chronic high fat, sucrose, and sodium intake.

We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47phox, and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.

Pitavastatin treatment normalizes VEGF signaling and cardiac function in STZ‐induced diabetic rat hearts

Abnormal alterations in cardiac expression of vascular endothelial growth factor (VEGF) as well as its receptors and impairment in the development of coronary collaterals have recently been reported in diabetic subjects. However, the effectiveness of pharmacological intervention on these diabetic defects remains unsettled. Here, we studied the effects of statin (pitavastatin) on cardiac VEGF signaling pathways and cardiac function in Sprague‐Dawley rats 5 wk after induction of type I diabetes with streptozotocin (65 mg/kg ip) in comparison with age‐matched control rats. After streptozotocin (1 wk), some diabetic rats were treated with pitavastatin (1 mg/day) for 4 wk. VEGF, its receptors, and its angiogenic signaling molecules [phosphorylated Akt and endothelial nitric‐oxide synthase (eNOS)] were analyzed by Western blot, ELISA, real‐time PCR, and immunohistochemistry, and cardiac function was evaluated by echocardiography. Coronary capillary morphology was assessed by lectin and enzymatic double staining. We found significant decreases in cardiac expression of VEGF, its receptors, phosphorylation of Akt and eNOS, and coronary capillary density in diabetic rats compared with controls. Treatment of diabetic rats with pitavastatin reversed these alterations to control levels and ameliorated impairment of cardiac function. The present study is the first to show the potential usefulness of a statin in the treatment of cardiac dysfunction in type I diabetes at the molecular level.

Effect of hypothermia on coagulation functions in Sprague-Dawley rats with uncontrolled hemorrhagic shock

Acute coagulopathy, hypothermia, and acidosis are known as the lethal triad of major trauma patients. Major trauma patients with hypothermia and acidosis developed clinically significant bleeding despite adequate transfusion [1]. Recent animal experiment studies reported that hypothermia is associated with improved survival in controlled hemorrhagic shock [2,3]. Post-traumatic hypothermia is an unproven therapy unlike hypothermia as a postcardiac arrest care. The objective of this study was to investigate the effect of hypothermia on coagulation function in uncontrolled hemorrhagic shock with major trauma.

E0184 The protection effects of trimetazidine on rats myocardial infraction

ObjectiveTo observe the myocardial protection effects of trimetazidine on Sprague-Dawley (SD) rats with myocardial infarctions (MI).Methods90 SD rats were randomly assigned to normal control group (NL, n=30), Trimetazidine group (T,...

Acute Effects of Hypercholesterolemic Diet on Erectile Responses in Rats

Objective: The aim of this study was to evaluate the acute effects of a high cholesterol diet (HCD) on erectile and endothelial functions in Sprague-Dawley rats. Materials and Methods: Sprague-Dawley rats were divided into 2 groups as control and HCD groups. The control group was fed on a normal diet and the hypercholesterolemia group was fed a 1% cholesterol-enriched diet daily for 2 weeks. Total cholesterol levels were measured at the end of 2 weeks in both groups. To examine the effect of HCD on erectile function, electric cavernous nerve stimulation (CNS) at 20 Hz with a pulse duration of 1 ms for 1 min at 5 V was performed. During CNS, we measured intracavernous pressure (ICP), mean arterial pressure (MAP), detumescence time and area under the curve (AUC). To evaluate the endothelial responses, acetylcholine (Ach) was applied cumulatively (1 nM to 1 µM) to thoracic aorta tissues contracted with 60 mM KCl. Results: In the HCD group total cholesterol levels were significantly higher than in the control group (148.1 ± 18.9 vs. 55.7 ± 8.1 mg/dl, p = 0.002). The detumescence time was significantly decreased after HCD compared to the control diet (19.3 ± 3.6 vs. 78.6 ± 12.8 s, p < 0.001). The decreases in the HCD group were also significant in terms of ICP (53.4 ± 4.5 vs. 35.6 ± 5.5 mm Hg; p < 0.05), ICP/MAP (55.9 ± 3.9 vs. 38.2 ± 5.2%; p < 0.05) and AUC (1,404 ± 197.1 vs. 2,250 ± 253.7, p < 0.05) values. There were no significant changes in maximum relaxation responses of the thoracic aorta to Ach. Conclusion: These results suggest that erectile functions were significantly damaged early in HCD rats. However, endothelial functions, evaluated in the thoracic aorta, were not affected simultaneously with erectile functions in rats fed a low concentration of HCD.

Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE

We have previously reported that adenoviral-mediated delivery of cytochrome P-450 (CYP) 4A2, which catalyzes the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), results in endothelial dysfunction and hypertension in Sprague-Dawley (SD) rats (Wang JS, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, Wolin MS, Hintze TH, Abraham NG, Nasjletti A, Laniado-Schwartzman M. Circ Res 98: 962-969, 2006). In this study, we targeted the vascular endothelium by using a lentivirus construct expressing CYP4A2 under the control of the endothelium-specific promoter VE-cadherin (VECAD-4A2) and examined the effect of long-term CYP4A2 overexpression on blood pressure and kidney function in SD rats. A bolus injection of VECAD-4A2 increased blood pressure (P < 0.001) by 26, 36, and 30 mmHg 10, 20, and 30 days postinjection, respectively. Arteries from VECAD-4A2-transduced rats produced increased levels of 20-HETE (P < 0.01), expressed lower levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) (P < 0.05), generated higher levels of superoxide anion, and displayed decreased relaxing responsiveness to acetylcholine (P < 0.05). Proteinuria increased by twofold in VECAD-4A2-transduced rats compared with controls. Treatment of VECAD-4A2-transduced rats with HET0016, an inhibitor of 20-HETE biosynthesis, not only attenuated the increase in blood pressure (P < 0.05) but also improved vascular function (acetylcholine-induced relaxations) and reduced plasma creatinine and proteinuria. HET0016 treatment decreased oxidative stress and increased the phosphorylated state of key proteins that regulate endothelial function, including eNOS, AKT, and AMPK. Collectively, these findings demonstrate that augmentation of vascular endothelial 20-HETE levels results in hypertension, endothelial dysfunction, and renal injury, which is offset by HET0016 through a reduction in vascular 20-HETE coupled with a lessening of oxidative stress and the amplification of pAKT, pAMPK, and p-eNOS levels leading to normalization of endothelial responses.

Suppression of Diet-Induced Hypercholesterolemia by Scutellarin in Rats

Hypercholesterolemia is a major risk factor for the development and progression of cardiovascular diseases including atherosclerosis. A major active ingredient, scutellarin, from the plant Erigeron breviscapus was investigated for its hypocholesterolemic and atheroscleroprotective effects (30 and 100 mg/kg/day, P. O.). The serum lipid profile (total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol) was monitored and aortic functions in Sprague-Dawley rats fed with normal diet, atherogenic diet or atherogenic diet plus oral administration of either scutellarin or simvastatin (a positive control) were tested. It was found that scutellarin markedly attenuated the increased serum total cholesterol induced by atherogenic diet. It caused a significant reduction in the atherogenic index. In addition, scutellarin administration could significantly enhance acetylcholine-induced nitrate/nitrite production, increase the gene expression of endothelial nitric oxide synthase and improve acetylcholine-induced endothelium-dependent vasorelaxation in rat isolated aortas. These data revealed that scutellarin could reduce the atherogenic properties of dietary cholesterol in rats. However, whether scutellarin's atheroscleroprotective potential targets endothelial function directly or indirectly on its antioxidative activity remains to be determined.

17β-Estradiol deficiency reduces potassium excretion in an angiotensin type 1 receptor-dependent manner

This study examined the effects of ovariectomy (OVX) and 17beta-estradiol (E(2)) replacement (OVX + E(2)) on renal function in Sprague-Dawley rats. OVX caused a 40% decrease in the fractional excretion of potassium (FE(K(+))) that was prevented by E(2) replacement [Sham, 24.2 +/- 2.9%; OVX, 14.5 +/- 2.1% (P < 0.05 vs. OVX + E(2)); and OVX + E(2), 26.2 +/- 2.7%; n = 7-11] and that corresponded to significant increases in plasma potassium [(in mmol/l): Sham, 3.15 +/- 0.087; OVX, 3.42 +/- 0.048 (P < 0.05 vs. OVX + E(2)); and OVX + E(2), 3.19 +/- 0.11; n = 7-11]. No effects of OVX were detected on plasma levels of sodium and aldosterone. Angiotensin II type 1 receptor (AT(1)R) densities in ovariectomized rats were 1.4-fold and 1.3-fold higher in glomerular [maximum binding capacity (B(max); in fmol/mg protein): Sham, 482 +/- 21; OVX, 666 +/- 20 (P < 0.05 vs. OVX + E(2)); and OVX + E(2), 504 +/- 26; n = 7-11] and proximal tubular [B(max) (in fmol/mg protein): Sham, 721 +/- 16; OVX, 741 +/- 24 (P < 0.05 vs. OVX + E(2)); and OVX + E(2), 569 +/- 23; n = 7-11] membranes compared with E(2) replete animals, respectively. Both the angiotensin-converting enzyme inhibitor captopril and the AT(1)R antagonist losartan prevented the OVX-induced decrease in the FE(K(+)) and the increase in renal AT(1)R densities, suggesting that E(2) deficiency reduces potassium excretion in an ANG II/AT(1)R-dependent manner. These findings may have implications for renal function in postmenopausal women as well as contribute to the reasons underlying the age-induced increase in susceptibility to hypertension-associated disease in women.

Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts

Abnormal alterations in cardiac expression of vascular endothelial growth factor (VEGF) as well as its receptors and impairment in the development of coronary collaterals have recently been reported in diabetic subjects. However, the presence of pharmacological intervention on these defects in diabetes remains unsettled. Here, we studied the effect of endothelin (ET) receptor blockade on cardiac VEGF signaling pathways and cardiac function in Sprague-Dawley rats 5 wk after induction of type I diabetes with streptozotocin (65 mg/kg ip) in comparison with age-matched control rats. After streptozotocin (1 wk), some diabetic rats were treated with the ET receptor antagonist SB-209670 (1 mg/day) for 4 wk. VEGF, its receptors, and its angiogenic signaling molecules [phosphorylated Akt and endothelial nitric-oxide synthase (eNOS)] were analyzed by Western blot, ELISA, real-time PCR, and immunohistochemistry, and cardiac function was evaluated by echocardiography. Coronary capillary morphology was assessed by lectin and enzymatic double staining. We found significant decreases in cardiac expression of VEGF, its receptors, phosphorylation of Akt and eNOS, and coronary capillary density in diabetic rats compared with controls. Treatment of diabetic rats with SB-209670 reversed these alterations to the control levels and ameliorated impairment of cardiac function. From a molecular point of view, the present study is the first to indicate the potential usefulness of an ET receptor antagonist in the treatment of cardiac dysfunction in type I diabetes.