Function In Healthy Rats Research Articles

Multimodal Imaging Reveals that Sustained Inhibition of HIF-Prolyl Hydroxylases Induces Opposing Effects on Right and Left Ventricular Function in Healthy Rats.

Hypoxia-inducible factor (HIF) drives transcription of critical hypoxia response genes, increasing the production of red blood cells in low oxygen conditions. In the absence of hypoxia, HIF is degraded by prolyl hydroxylases (HIF-PHs). Pharmacological HIF-PH inhibition stabilizes HIF and is being studied as a treatment for anemia. However, like sustained hypoxia, HIF-PH inhibition may increase pulmonary arterial pressure leading to right ventricular hypertrophy. The aim of this study was to assess the cardiac effects of sustained pharmacological HIF-PH inhibition using multimodal imaging, blood analysis, and histology. Rats were dosed daily with a pan HIF-PH inhibitor or vehicle for 4weeks followed by a 2-week washout period and underwent longitudinal magnetic resonance imaging (MRI) and echocardiography to simultaneously assess RV and LV function. Blood samples from weeks four and six were analyzed to determine red blood cell composition. Histology was performed on the cardiac tissue from a subset of rats at weeks four and six to assess structural effects. Imaging revealed that RV ejection fraction was reduced in animals receiving HIF-PH inhibitor and resulted in RV hypertrophy. Interestingly, HIF-PH inhibition had the opposite effect on the left ventricle (LV), increasing contractility measured by LV ejection fraction. LV effects were reversed by week six, while RV effects (functional and structural) were sustained. These opposing cardiac effects of HIF-PH inhibition warrant further study to both understand the potential negative effects on RV structure and function and investigate the therapeutic potential of increased LV contractility for conditions like heart failure.

Effect of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function in healthy rats based on intestinal flora

To observe the effects of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function and intestinal flora in healthy rats, thereby investigating the underlying mechanism of moxibustion on immune function. Twenty 8-week-old SD rats were randomly divided into a young blank group and a young moxibustion group, with 10 rats in each group. Similarly, twenty 8-month-old SD rats were randomly divided into a middle-aged blank group and a middle-aged moxibustion group, with 10 rats in each group. The rats in the two moxibustion groups received moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4), 15 min per session, once daily, five times a week, for a total of four months. The rats in the two blank groups were fed under normal conditions. After the intervention, thymus and spleen indexes were calculated; the morphology of thymus and spleen tissues was observed using HE staining; the flow cytometry was used to detect the expression of CD and CD T lymphocytes and the CD/CD ratio was calculated; ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17); 16S rRNA high-throughput sequencing was used to analyze the intestinal flora. Additionally, the correlation between the relative abundance of intestinal flora and serum levels of TNF-α, IFN-γ, IL-6, IL-10 and IL-17 was analyzed. Compared with the young blank group, the young moxibustion group exhibited an increase in the cortical area of thymus tissue with tighter lymphocyte arrangement; compared with the middle-aged blank group, the middle-aged moxibustion group showed an increase in thymus index (P<0.05) and an increase in the cortical area of thymus tissue. There were no significant differences in spleen index between the 2 moxibustion groups and the 2 blank groups (P>0.05). There were no significant differences in the expression of CD, CD, and CD/CD ratio between the 2 moxibustion groups and the corresponding blank groups (P>0.05). Compared with the young blank group, the young moxibustion group had elevated IL-6 level (P<0.05); compared with the middle-aged blank group, the middle-aged moxibustion group had decreased IL-10 and IL-17 levels (P<0.05). Compared with the young blank group, the young moxibustion group exhibited increased Sobs index, Ace index, and Chao index (P<0.01, P<0.05), as well as increased relative abundance of Spirochaetota, Treponema, Turicibacter, Rikenellaceae_RC9_gut_group (P<0.05), and decreased relative abundance of Dubosiella (P<0.05). Compared with the middle-aged blank group, the middle-aged moxibustion group had increased relative abundance of Spirochaetota, Treponema, norank_f_Peptococcaceae (P<0.05), and decreased relative abundance of Proteobacteria, Allobaculum, and Faecalibaculum (P<0.05). Correlation analysis revealed that relative abundance of Eubacterium_xylanophilum_group and unclassified _f_Lachnospiraceae was negatively correlated with serum TNF-α level (r=-0.39, P=0.03; r=-0.24, P=0.04), while relative abundance of norank_f_norank_o_Clostridia_UCG-014 and Lactobacillus was positively correlated with serum TNF-α level (r=0.37, P=0.04; r=0.43, P=0.02). The relative abundance of Roseburia and Monoglobus was negatively correlated with serum IFN-γ level (r=-0.40, P=0.02; r=-0.44, P=0.01), while relative abundance of Lactobacillus was positively correlated with serum IL-10 level (r=0.43, P=0.02). Moxibustion could improve immune function in healthy rats, and its mechanism may be related to the regulation of relative abundance of intestinal flora.

Effects of Different Doses of Eucalyptus Oil From Eucalyptus globulus Labill on Respiratory Tract Immunity and Immune Function in Healthy Rats

Eucalyptol (1,8-cineole), the major constituent of eucalyptus oil (EO), was used in traditional medicine as a remedy for colds and bronchitis. This study aimed at clarifying the effect of eucalyptol on respiratory immune function of CD8 and CD4 cells, and alveolar macrophages (AM). Thirty male Sprague-Dawley rats were divided into experimental and control groups. The drug was given once a day for 3 weeks and the experimental group was divided according to the eucalyptol dose into: 30, 100, and 300 mg·kg-1 groups. Flow cytometry was used to detect the phagocytic function of CD4, CD8 cells, and AM in the bronchopulmonary lavage fluid. The 30 and 100 mg·kg-1 groups had an up-regulation effect on CD8 (p < 0.05), with no significant effect on macrophage phagocytosis. The 300 mg·kg-1 group had an inhibitory effect on CD8 and macrophage phagocytosis (p < 0.05), with no significant difference in CD4 between groups. Further investigation was conducted to evaluate the effect of EO on immune function in rats by detecting blood T, B, and NK cells using flow cytometry, and blood IgA, IgG, IgM, and IFN-γ levels by ELISA. High dosage of eucalyptol significantly reduced the proportion of blood B and NK cells (p < 0.05). IgA was decreased in the 100 and 300 mg·kg-1 groups (p < 0.05). There are no significant differences between the number of T cells and the IgG, IgM, and IFN-γ levels between experimental and control groups. Rational use of EO containing eucalyptol can improve the immune function of the respiratory tract and the body immunity, while high dose could have damaging effects, through modifying the phagocytic function of CD8 cells and reducing the proportion of blood B cells, NK cells, and IgA.

11C-PABA as a PET Radiotracer for Functional Renal Imaging: Preclinical and First-in-Human Study.

para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-h urine sampling. Therefore, we hypothesized that PABA radiolabeled with 11C might allow high-quality dynamic PET of the kidneys with less radiation exposure than other agents because of its shorter biologic and physical half-life. We evaluated if 11C-PABA can visualize renal anatomy and quantify function in healthy rats and rabbits and in a first-in-humans study on healthy volunteers. Methods: Healthy rats and rabbits were injected with 11C-PABA intravenously. Subsequently, dynamic PET was performed, followed by postmortem tissue-biodistribution studies. 11C-PABA PET was directly compared with the current standard, 99mTc-mercaptoacetyltriglycin, in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of 11C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of 11C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, 11C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then pelvis with high spatiotemporal resolution. Conclusion:11C-PABA demonstrated fast renal excretion with a very low background signal in animals and humans. These results suggest that 11C-PABA might be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.

Influence of isoniazid on T lymphocytes, cytokines, and macrophages in rats

T lymphocytes, cytokines, and macrophages play important roles in the clearance of Mycobacterium tuberculosis (Mtb) by the immune system. This study aimed to investigate the effects of isoniazid on the functions of both innate and adaptive immune cells. Healthy rats were randomly divided into experimental and control groups. Each group was randomly divided into three subgroups and named according to the duration of drug feeding, 1, 3, and 3 months followed by drug withdrawal for 1 month. The experimental groups were fed with isoniazid (12 mg/mL) and the control groups with normal saline. The percentage of CD4+ and CD8+ T lymphocytes, level of interleukin (IL)-12 and interferon (IFN)-γ, and function of macrophages were determined at these three time points. Isoniazid significantly increased the percentage of CD4+ T lymphocytes and the CD4+/CD8+ T lymphocyte cell ratio (P < 0.05). It transiently (<1 month) enhanced the functions of rat macrophages significantly (P < 0.05). In summary, isoniazid could increase the percentage of CD4+ T lymphocytes, CD4+/CD8+ T lymphocyte cell ratio, and enhance macrophage function in healthy rats.

High intensity training improves cardiac function in healthy rats

Exercise training is a low cost and safe approach for reducing the risk of cardiovascular disease development. Currently, moderate-intensity training (MIT) is the most preferred exercise type. However, high-intensity interval training (HIIT) is gaining interest especially among athletes and healthy individuals. In this study, we examined cardiac remodeling resulting from MIT and HIIT in healthy rats. Healthy male Sprague-Dawley rats were randomly assigned to MIT or HIIT for 13 weeks. Animals kept sedentary (SED) were used as control. Cardiac function was evaluated with echocardiography and hemodynamic measurements. Heart tissue was stained for capillary density and fibrosis. After 13 weeks of training, only HIIT induced beneficial cardiac hypertrophy. Overall global cardiac parameters (such as ejection fraction, cardiac output and volumes) were improved similarly between both training modalities. At tissue level, collagen content was significantly and similarly reduced in both exercise groups. Finally, only HIIT increased significantly capillary density. Our data indicate that even if very different in design, HIIT and MIT appear to be equally effective in improving cardiac function in healthy rats. Furthermore, HIIT provides additional benefits through improved capillary density and should therefore be considered as a preferred training modality for athletes and for patients.

Abnormal cannabidiol confers cardioprotection in diabetic rats independent of glycemic control

Chronic GPR18 activation by its agonist abnormal cannabidiol (trans-4-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol; abn-cbd) improves myocardial redox status and function in healthy rats. Here, we investigated the ability of abn-cbd to alleviate diabetes-evoked cardiovascular pathology and the contribution of GPR18 to this effect. Four weeks after diabetes induction by streptozotocin (STZ, 55mg/kg; i.p), male Wistar rats received abn-cbd, the GPR18 antagonist (1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-,cyclohexen-1-yl]benzene;O-1918), their combination (100µg/kg/day, i.p, each) or their vehicle for 2 weeks. Abn-cbd had no effect on diabetes-evoked cardiac hypertrophy or impaired glycemic control (hyperglycemia and hypoinsulinemia), but alleviated the associated reductions in left ventricular (LV) contractility (dP/dtmax) and relaxation (dP/dtmin) indices, and the increases in LV end diastolic pressure (LVEDP) and cardiac vagal dominance. Abn-cbd also reversed myocardial oxidative stress by restoring circulating and cardiac nitric oxide (NO) and adiponectin (ADN) levels and enhancing GPR18 expression and phosphorylation of Akt, ERK1/2 and eNOS in diabetic rats’ hearts. Concurrent GPR18 blockade (O-1918) abrogated all favorable effects of abn-cbd in diabetic rats. Collectively, the current findings present evidence for abn-cbd alleviation of diabetes-evoked cardiovascular anomalies likely via GPR18 dependent restoration of cardiac adiponectin-Akt-eNOS signaling and the diminution of myocardial oxidative stress.

Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s-1, SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s-1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s-1, MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive.NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function.

Hydroalcoholic extract and pure compounds from Senecio nutans Sch. Bip (Compositae) induce vasodilation in rat aorta through endothelium-dependent and independent mechanisms

Ethnopharmacological relevanceSenecio nutans Sch. Bip. (Compositae) is an endemic plant of South America, and is used in herbal medicine in Andean communities for treating acute mountain sickness. Currently, the direct effects of hydroalcoholic extract of S. nutans (HAE S. nutans) or its isolated compounds on the vascular system are not well described. The aim of this study was to determine the effects and mechanism of action of S. nutans on vascular function in healthy rats. Material and methodsSeven compounds were isolated from the HAE S. nutans, and their structures were characterized using spectroscopic techniques as 1D and 2D NMR, and mass spectrometry. Vascular reactivity experiments were carried out in rat aorta. S. nutans-dependent vasodilation and phenylephrine-dependent contraction were measured in endothelium-intact and endothelium-denuded aortic rings of male rats. ResultsSeven pure compounds were isolate from HAE S. nutans, but two pure compounds showed significant vasodilation in rat aorta: 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (compound E) and 5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane (compound G). Although HAE S. nutans induced vasodilation in absence of endothelium, the vasodilation in intact aorta, via NO, was higher. HAE S. nutans reduced calcium-dependent contraction in endothelium-intact, but not in endothelium-denuded aortic rings. ConclusionHAE S. nutans and its isolated compounds caused vasodilation in rat aorta in absence of endothelium, suggesting its vasodilator properties is endothelium-dependent (NO) and or independent, and may involve a modulation of the calcium channels. This result is of clinical interest as potential therapy control of blood pressure.

Endurance training prevents negative effects of the hypoxia mimetic dimethyloxalylglycine on cardiac and skeletal muscle function.

Hypoxic preconditioning is a promising strategy to prevent hypoxia-induced damages to several tissues. This effect is related to prior stabilization of the hypoxia-inducible factor-1α via inhibition of the prolyl-hydroxylases (PHDs), which are responsible for its degradation under normoxia. Although PHD inhibition has been shown to increase endurance performance in rodents, potential side effects of such a therapy have not been explored. Here, we investigated the effects of 1 wk of dimethyloxalylglycine (DMOG) treatment (150 mg/kg) on exercise capacity, as well as on cardiac and skeletal muscle function in sedentary and endurance-trained rats. DMOG improved maximal aerobic velocity and endurance in both sedentary and trained rats. This effect was associated with an increase in red blood cells without significant alteration of skeletal muscle contractile properties. In sedentary rats, DMOG treatment resulted in enhanced left ventricle (LV) weight together with impairment in diastolic function, LV relaxation, and pulse pressure. Moreover, DMOG decreased maximal oxygen uptake (state 3) of isolated mitochondria from skeletal muscle. Importantly, endurance training reversed the negative effects of DMOG treatment on cardiac function and restored maximal mitochondrial oxygen uptake to the level of sedentary placebo-treated rats. In conclusion, we provide here evidence that the PHD inhibitor DMOG has detrimental influence on myocardial and mitochondrial function in healthy rats. However, one may suppose that the deleterious influence of PHD inhibition would be potentiated in patients with already poor physical condition. Therefore, the present results prompt us to take into consideration the potential side effects of PHD inhibitors when administrated to patients.

Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond.

Influence of green and gold kiwifruit on indices of large bowel function in healthy rats.

The effects of kiwifruit on large bowel health were investigated in healthy rats. Four-week old Sprague-Dawley rats were given diets containing 10% homogenized green kiwifruit, gold kiwifruit or 10% glucose solution (control) over 4 or 6 wk. Green kiwifruit increased the fecal output compared to control. Growth of certain bacterial species in cecum was influenced by both green and gold kiwifruit. A significant increase in cecal Lachnospiraceae in rats fed the green kiwifruit diet was observed at week 4. At week 6, green and gold kiwifruit diets assisted in improving colonic barrier function by upregulating the expression of mucin (MUC)-2, MUC3, Toll-like receptor (TLR)-4 or trefoil factor-3 genes. Gold kiwifruit consumption increased the colonic goblet cells per crypt at week 6. Significant negative correlations between E. coli and β-defensin 1 and TLR4 expression were observed. Consuming green and gold kiwifruit for 6 wk significantly altered the biomarkers of large bowel health; indicating that regularly consuming kiwifruit helps attain optimal digestive health.

PM332 Nicotine impairs cardiac function in healthy rats: Comparison between low and moderate doses

PM332 Nicotine impairs cardiac function in healthy rats: Comparison between low and moderate doses

Vasoactive effects of prostaglandins from the perivascular fat of mesenteric resistance arteries in WKY and SHROB rats

AimsWe have studied the vasoactive role of prostaglandins derived from perivascular adipose tissue (PVAT) and their effects on endothelial function in healthy rats and rats with metabolic syndrome (SHROB). Main methodsMesenteric resistance arteries (MRA) from SHROB and control rats (WKY) were mounted on wire myographs: a) together with a sphere of naturally occurring perivascular adipose tissue (with-PVAT group), or b) dissecting all the adventitial tissue (without-PVAT group). Key findingsEndothelial function, tested by acetylcholine reactivity of SHROB arteries with PVAT, was significantly lower than that of WKY. With-PVAT arteries, especially the SHROB, showed lower responses than those without PVAT. NO synthase inhibition diminished the acetylcholine responses in every group except the with-PVAT SHROB group. Blockade of cyclooxygenase-2, PGI2-IP, TXA2-TP, or TXA2 synthase increased to different extents the arterial responses in the SHROB with-PVAT group. PVAT from both rat strains revealed cyclooxygenase-2 activity and immunoassay confirmed the release of PGE2, PGI2 and TXA2. SignificanceOur major finding is that PVAT is a source of vasoactive prostaglandins in WKY and SHROB. We also report that the presence of visceral PVAT causes endothelial dysfunction of resistance arteries in the SHROB. The vascular responses to prostaglandins partly underlie the endothelial dysfunction of SHROB arteries.

Positron emission tomography in the assessment of left ventricular function in healthy rats: A comparison of four imaging methods

ObjectiveTo measure left ventricular (LV) function parameters in heart of healthy rats by three different positron emission tomography (PET) imaging techniques and by magnetic resonance imaging (MRI). MethodsECG-gated microPET examinations were obtained in seven healthy rats with 2-deoxy-2-[18F]fluoro-d-glucose (FDG) for calculation of LV-function from the blood-pool phase of the dynamic recording (FDGBP), and also from the later myocardial uptake (FDGMyo). On subsequent days, we re-measured LV-function using the novel blood-pool tracer 68Ga-albumin (AlbBP) and again by FDG (FDGMyo2) in one setting. Cine-MRI examination provided the reference standard measurement. ResultsThe mean LV ejection fractions (LVEF) were 56 ± 3 (FDGBP), 55 ± 3 (FDGMyo), 56 ± 3 (FDGMyo2), 57 ± 3 (AlbBP), and 57 ± 2 (MRI). There were good to excellent correlations found between the LVEF-values as compared to MRI reference standard for FDGBP (r = 0.71), FDGMyo (r = 0.86) and AlbBP (r = 0.88). Both of the blood-pool methods significantly overestimated the magnitudes of end-diastolic-volume and end-systolic-volume, whereas FDGMyo matched closely to the MRI reference standard. There was no significant bias for both blood-pool methods and a minor negative bias for FDGMyo regarding the LV ejection fraction (LVEF) when compared to cine-MRI results. There was no significant difference between the means of FDGMyo and FDGMyo2 (P = .50). ConclusionsRelative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer 68Ga-albumin.

Ageing-induced decrease in cardiac mitochondrial function in healthy rats

It is widely recognized that mitochondrial dysfunction is a key component of the multifactorial process of ageing. The effects of age on individual components of mitochondrial function vary across species and strains. In this study we investigated the oxygen consumption, the mitochondrial membrane potential (Δψ), the sensitivity of mitochondrial permeability transition pore (mPTP) to calcium overload, and the production of reactive oxygen species (ROS) in heart mitochondria isolated from old compared with adult healthy Sprague-Dawley rats. Respirometry studies and Δψ measurements were performed with an Oxygraph-2k equipped with a tetraphenylphosphonium electrode. ROS production and calcium retention capacity were measured spectrofluorimetrically. Our results show an important decline for all bioenergetic parameters for both complex I and complex II supported-respiration, a decreased Δψ in mitochondria energized with complex I substrates, and an increased mitochondrial ROS production in the old compared with the adult group. Mitochondrial sensitivity to Ca²⁺-induced mPTP opening was also increased in the old compared with the adult animals. Moreover, the protective effect of cyclosporine A on mPTP opening was significantly reduced in the old group. We conclude that healthy ageing is associated with a decrease in heart mitochondria function in Sprague-Dawley rats.

Environmentally persistent free radicals decrease cardiac function and increase pulmonary artery pressure

Epidemiological studies have consistently linked inhalation of particulate matter (PM) to increased cardiac morbidity and mortality, especially in at risk populations. However, few studies have examined the effect of PM on baseline cardiac function in otherwise healthy individuals. In addition, airborne PM contain environmentally persistent free radicals (EPFR) capable of redox cycling in biological systems. The purpose of this study was to determine whether nose-only inhalation of EPFRs (20 min/day for 7 days) could decrease baseline left ventricular function in healthy male Sprague-Dawley rats. The model EPFR tested was 1,2-dichlorobenzene chemisorbed to 0.2-μm-diameter silica/CuO particles at 230°C (DCB230). Inhalation of vehicle or silica particles served as controls. Twenty-four hours after the last exposure, rats were anesthetized (isoflurane) and ventilated (3 l/min), and left ventricular function was assessed using pressure-volume catheters. Compared with controls, inhalation of DCB230 significantly decreased baseline stroke volume, cardiac output, and stroke work. End-diastolic volume and end-diastolic pressure were also significantly reduced; however, ventricular contractility and relaxation were not changed. DCB230 also significantly increased pulmonary arterial pressure and produced hyperplasia in small pulmonary arteries. Plasma levels of C-reactive protein were significantly increased by exposure to DCB230, as were levels of heme oxygenase-1 and SOD2 in the left ventricle. Together, these data show that inhalation of EPFRs, but not silica particles, decreases baseline cardiac function in healthy rats by decreasing cardiac filling, secondary to increased pulmonary resistance. These EPFRs also produced systemic inflammation and increased oxidative stress markers in the left ventricle.

1576 INHIBITION OF SPINAL FATTY ACID AMIDE HYDROLASE MODIFIES MICTURITION DURING CYSTOMETRY IN AWAKE RATS

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20121576 INHIBITION OF SPINAL FATTY ACID AMIDE HYDROLASE MODIFIES MICTURITION DURING CYSTOMETRY IN AWAKE RATS Claudius Fullhase, Giorgio Gandaglia, Fabio Benigni, Christian Gratzke, Christian Stief, Patrizio Rigatti, Francesco Montorsi, and Petter Hedlund Claudius FullhaseClaudius Fullhase Munich, Germany More articles by this author , Giorgio GandagliaGiorgio Gandaglia Milan, Italy More articles by this author , Fabio BenigniFabio Benigni Milan, Italy More articles by this author , Christian GratzkeChristian Gratzke Munich, Germany More articles by this author , Christian StiefChristian Stief Munich, Germany More articles by this author , Patrizio RigattiPatrizio Rigatti Milan, Italy More articles by this author , Francesco MontorsiFrancesco Montorsi Milan, Italy More articles by this author , and Petter HedlundPetter Hedlund Lund, Sweden More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1348AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Fatty acid amide hydrolase (FAAH), a key enzyme for the degradation of endocannabinoids, is expressed in the urinary bladder and a peripheral regulatory function for FAAH in micturition is proposed. It is not known if central nervous FAAH may be of functional importance for the micturition reflex. This study evaluated the effect of intrathecal (i.t.) administration of the FAAH inhibitor oleoyl ethyl amide (OEtA) on bladder function in healthy rats. METHODS After ethical approval, female Sprague Dawley rats (n=12) under anesthesia received a polyethylene (PE)-10 intrathecal (i.t.) catheter (sacral level) for drug administration, and a PE-50 bladder catheter for urodynamic investigation. Three days postoperatively, cystometries were performed in awake rats and effects of i.t. OEtA (3,30, or 300nmol) or vehicle were assessed. Results are given as mean ±SEM. ANOVA was used for statistics. Values are mean±SEM. RESULTS Micturition intervals amounted to 5.5±0.7 (baseline), 6.4±0.6 (OEtA 3nmol; p<0.05), 7.2±0.4 (OEtA 30nmol; p<0.05), and 7.9±0.6 min (OEtA 300nmol; p<0.01). Micturition volumes were 0.80±0.11 (baseline), 0.97±0.11 (OEtA 3nmol; p=0.05), 1.13±0.09 (OEtA 30nmol; p<0.05), and 1.09±0.6 ml (OEtA 300nmol; p=0.05). Whereas 300nmol OEtA increased residual volume (RV) from 0.09±0.04 (baseline) to 0.22±0.08 (p<0.05), no effects on RV were recorded at 3 or 30nmol of OEtA. Bladder capacities were 0.90±0.11 (baseline), 1.07±0.10 (OEtA 3nmol; p=0.06), 1.20±0.08 (OEtA 30nmol; p<0.05), and 1.31±0.10 ml (OEtA 300nmol; p<0.05). At any investigated dose of OEtA (i.t.), no effects were noted for basal pressure, maximum micturition pressure, or area under the pressure curve. Threshold pressure (TP) amounted to 15.1±2.0 (baseline), and 22.6±4.8 (OEtA 300nmol; p<0.05). Flow pressure (FP) amounted to 25.4±3.7 (baseline), and 32.5±5.3 (OEtA 300nmol; p<0.05). At 3 and 30nmol of OEtA, a trend (p=0.08) for higher TP and FP was noted. Vehicle (i.t.) had no effects on intervals, volumes or pressures. Vehicle (i.t.) had no effect on urodynamic parameters. CONCLUSIONS Intrathecal administration of the FAAH inhibitor OEtA prolonged micturition intervals, increased micturition volumes, and bladder capacity without affecting basal and maximal bladder pressures. At the highest dose, OEtA also increased residual volume, threshold pressure and flow pressure. These findings suggest that FAAH and putatively endocannabinoids have a role in spinal regulation of afferent signals of the micturition reflex. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e638-e639 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claudius Fullhase Munich, Germany More articles by this author Giorgio Gandaglia Milan, Italy More articles by this author Fabio Benigni Milan, Italy More articles by this author Christian Gratzke Munich, Germany More articles by this author Christian Stief Munich, Germany More articles by this author Patrizio Rigatti Milan, Italy More articles by this author Francesco Montorsi Milan, Italy More articles by this author Petter Hedlund Lund, Sweden More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Tungstate Treatment Improves Leydig Cell Function in Streptozotocin‐Diabetic Rats

Oral administration of sodium tungstate to adult male streptozotocin-diabetic rats for 3 months normalized serum levels of glucose, insulin, luteinizing hormone, and follicle-stimulating hormone. These effects were accompanied by an increase in reproductive performance, which was related to a strong improvement in Leydig cell function markers, such as the recovery of the number of Leydig cells and serum testosterone levels. Moreover, this in vivo recovery was related to a concomitant increase in the cell expression of insulin receptors. Tungstate treatment did not modify Leydig cell function in healthy rats. Furthermore, the addition of tungstate or insulin to the mTLC-1 cell line from Leydig cell origin increased the phosphorylation states of MAP-kinase and glycogen synthase kinase-3. Our results indicate that tungstate treatment in diabetic rats leads to a recovery of reproductive performance by increasing the number of Leydig cells. This increase contributes to the recovery of their functionality, thereby improving the overall function of these cells. We propose that this improvement is caused by the combined effect of the tungstate-induced normalization of insulin glucose and luteinizing hormone serum levels and a direct action of the effector on Leydig cells through modulation of at least MAP-kinase and glycogen synthase kinase-3 activities.

Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats

Echinacea plant extract is widely used for the prevention and the treatment of upper respiratory tract infections. However, the active components in the herb, their optimal dosages and their in vivo effects are still undefined. Using male Sprague–Dawley rats (425–475 g), an in vivo study was conducted to examine the immunomodulatory effects of various dose levels of three components, isolated and purified from Echinacea purpurea. The components were cichoric acid, polysaccharides and alkylamides. The rats were gavaged orally two times/day for 4 days with three different concentrations of each of the Echinacea components. Among the components, alkylamides at the dose level of 12 μg/kg body weight/day significantly increased the phagocytic activity as well as phagocytic index of the alveolar macrophages. The alveolar macrophages obtained from this group of rats also produced significantly more TNF-α and nitric oxide after an in vitro stimulation with LPS than any other active component or the control. None of the components at any concentration had any effect on the release of TNF-α, IFN-γ and IL-2 by the splenocytes. These results suggest that the alkylamides are one of the active constituents of E. purpurea plant. At a dose level of approximately 12 μg/kg body weight/day they effectively stimulate alveolar macrophage function in healthy rats. The immunomodulatory effects of alkylamides appear to be more pronounced in lungs than in spleen.