Project description:Epoxyeicosatrienoic acids (EETs) and their analogs have been identified as potent antihypertensive compounds with cardio- and renoprotective actions. Here, we examined the effect of EET-A, an orally active EET analog, and c-AUCB, an inhibitor of the EETs degrading enzyme soluble epoxide hydrolase, on the progression of post-myocardial infarction (MI) heart failure (HF) in normotensive Hannover Sprague-Dawley (HanSD) and in heterozygous Ren-2 transgenic rats (TGR) with angiotensin II-dependent hypertension. Adult male rats (12 weeks old) were subjected to 60-min left anterior descending (LAD) coronary artery occlusion or sham (non-MI) operation. Animals were treated with EET-A and c-AUCB (10 and 1 mg/kg/day, respectively) in drinking water, given alone or combined for 5 weeks starting 24 h after MI induction. Left ventricle (LV) function and geometry were assessed by echocardiography before MI and during the progression of HF. At the end of the study, LV function was determined by catheterization and tissue samples were collected. Ischemic mortality due to the incidence of sustained ventricular fibrillation was significantly higher in TGR than in HanSD rats (35.4 and 17.7%, respectively). MI-induced HF markedly increased LV end-diastolic pressure (Ped) and reduced fractional shortening (FS) and the peak rate of pressure development [+(dP/dt)max] in untreated HanSD compared to sham (non-MI) group [Ped: 30.5 ± 3.3 vs. 9.7 ± 1.3 mmHg; FS: 11.1 ± 1.0 vs. 40.8 ± 0.5%; +(dP/dt)max: 3890 ± 291 vs. 5947 ± 309 mmHg/s]. EET-A and c-AUCB, given alone, tended to improve LV function parameters in HanSD rats. Their combination amplified the cardioprotective effect of single therapy and reached significant differences compared to untreated HanSD controls [Ped: 19.4 ± 2.2 mmHg; FS: 14.9 ± 1.0%; +(dP/dt)max: 5278 ± 255 mmHg/s]. In TGR, MI resulted in the impairment of LV function like HanSD rats. All treatments reduced the increased level of albuminuria in TGR compared to untreated MI group, but neither single nor combined EET-based therapy improved LV function. Our results indicate that EET-based therapy attenuates the progression of post-MI HF in HanSD, but not in TGR, even though they exhibited renoprotective action in TGR hypertensive rats.
Project description:We performed deep sequencing of the miRNAs present in ~20 toxicologically relevant tissues in Sprague Dawley rats and used three independent analysis of the data to determine which miRNAs are tissue specific and tissue enriched.
Project description:Profiling of gain and loss of DNA fragments in HHR comparing control SDR. Two analyses were performed; sample 1, SDR (male) vs HHR (male) and sample 2, SDR (female) vs HHR (female).
Project description:Aging is a universal phenomenon involving the whole body and is characterized by metabolic and physiological decline, leading to cardiovascular defects and heart failure. To characterize the molecular basis of physiological cardiac aging, the proteomic profiles of Sprague Dawley rat hearts of 6, 22 and 30 months were analysed by DIGE and immunoblotting. Results indicate changes in myosin binding protein C, aldehyde dehydrogenase, serpins and sirtuin-3 which protects from the opening of the mitochondrial permeability transition pore induced by cyclophilin D increment. Conversely, an increase of fusion, a decrease of mitochondrial fission and the activation of the non-canonical autophagy pathway were observed. These results support the hypothesis of successful aging in this rat model.
Project description:Gene expression analysis in control and diabetic rats. Diabetes-induced erectile dysfunction in rat model of DM. 10 weeks of streptozotocin induced diabetes. F344 Rats. Keywords: other
Project description:We performed deep sequencing of the miRNAs present in ~20 toxicologically relevant tissues in Sprague Dawley rats and used three independent analysis of the data to determine which miRNAs are tissue specific and tissue enriched. We performed deep sequencing of miRNAs in 21 organs from 5 male Sprague Dawley rats and 23 organs from 5 female Sprague Dawley rats.
Project description:Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200?mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12-22% compared to control in the 100 and 200?mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200?mg/k/day. Liver weight increases were both dose- and exposure time-related and statistically significant at ?25?mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5??g/mL (10 to 200?mg/kg/day). A NOAEL of 10?mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ?25?mg/kg/day.
Project description:Laboratory rats such as the Sprague-Dawley (SD) rats are an important model for biomedical studies in relation to human physiological or pathogenic processes. Here we report the first catalog of microbial genes in fecal samples from Sprague-Dawley rats. The catalog was established using 98 fecal samples from 49 SD rats, divided in 7 experimental groups, and collected at different time points 30 days apart. The established gene catalog comprises 5,130,167 non-redundant genes with an average length of 750 bp, among which 64.6% and 26.7% were annotated to phylum and genus levels, respectively. Functionally, 53.1%, 21.8%,and 31% of the genes could be annotated to KEGG orthologous groups, modules, and pathways, respectively. A comparison of rat gut metagenome catalogue with human or mouse revealed a higher pairwise overlap between rats and humans (2.47%) than between mice and humans (1.19%) at the gene level. Ninety-seven percent of the functional pathways in the human catalog were present in the rat catalogue, underscoring the potential use of rats for biomedical research.