Regulation In Rats Research Articles

Modelling hemodynamics regulation in rats and dogs to facilitate drugs safety risk assessment.

Pharmaceutical companies routinely screen compounds for hemodynamics related safety risk. In vitro secondary pharmacology is initially used to prioritize compounds while in vivo studies are later used to quantify and translate risk to humans. This strategy has shown limitations but could be improved via the incorporation of molecular findings in the animal-based toxicological risk assessment. The aim of this study is to develop a mathematical model for rat and dog species that can integrate secondary pharmacology modulation and therefore facilitate the overall pre-clinical safety translation assessment. Following an extensive literature review, we built two separate models recapitulating known regulation processes in dogs and rats. We describe the resulting models and show that they can reproduce a variety of interventions in both species. We also show that the models can incorporate the mechanisms of action of a pre-defined list of 50 pharmacological mechanisms whose modulation predict results consistent with known pharmacology. In conclusion, a mechanistic model of hemodynamics regulations in rat and dog species has been developed to support mechanism-based safety translation in drug discovery and development.

Setting Treadmill Intensity for Rat Aerobic Training Using Lactate and Gas Exchange Thresholds.

To open up new horizons of translational research, we studied the lactate threshold (LT)-dependent physiological responses and adaptations to exercise in rats, highlighting the importance of intensity-specific studies for optimizing exercise prescriptions. LT is physiologically related to the non-invasive gas exchange threshold (GET), and both thresholds are moderate-heavy-intensity boundary indices in determining an effective intensity of aerobic training in humans. While their practical utility is presumed to extend to rats, the actual existence of GET, the thresholds' relations to maximal oxygen consumption (VO2max), and whether aerobic adaptations by training differ around the LT intensity remain uncertain. This study sought to identify the GET using our previously established rat LT-model by combining the use of a metabolic chamber and the V-slope method and to confirm the thresholds' relations to VO2max. We investigated changes in the thresholds and VO2max following 6 weeks of endurance training at below or above LT intensity. GET and LT were significantly correlated, and agreed with high precision, although with a fixed bias. Untrained rats exhibited GET and LT at 56% and 52% of their VO2max, respectively. Endurance training at supra-, but not below-, the LT intensity significantly improved VO2max and both thresholds; however, their %VO2max remained unaltered. GET in rats is identifiable as a threshold associated with LT using the V-slope method. Further, both thresholds can serve as moderate-heavy-intensity boundary indices for the aerobic training of rats. This study advances our understanding of exercise intensity regulation in rats, thereby contributing to the development of a more nuanced and effective model for exercise prescription, with implications for human health and fitness.

Linagliptin mitigates cisplatin-induced kidney impairment via mitophagy regulation in rats, with emphasis on SIRT-3/PGC-1α, PINK-1 and Parkin-2

Cisplatin (CDDP) often leads to kidney impairment, limiting its effectiveness in cancer treatment. The lack of mitophagy in proximal tubules exacerbates this issue. Hence, targeting SIRT-3 and PGC1-α shows promise in mitigating CDDP-induced kidney damage. The potential renoprotective effects of linagliptin, however, remain poorly understood. This study represents the first exploration of linagliptin's impact on CDDP-induced kidney impairment in rats, emphasizing its potential role in mitophagic pathways. The experiment involved four rat groups: Group (I) received saline only, Group (II) received a single intraperitoneal injection of CDDP at 6 mg/kg. Groups (III) and (IV) received linagliptin at 6 and 10 mg/kg p.o., respectively, seven days before CDDP administration, continuing for an additional four days. Various parameters, including renal function tests, oxidative stress, TNF-α, IL-1β, IL-6, PGC-1α, FOXO-3a, p-ERK1, and the gene expression of SIRT-3 and P62 in renal tissue, were assessed. Linagliptin improved renal function, increased antioxidant enzyme activity, and decreased IL-1β, TNF-α, and IL-6 expression. Additionally, linagliptin significantly upregulated PGC-1α and PINK-1/Parkin-2 expression while downregulating P62 expression. Moreover, linagliptin activated FOXO-3a and SIRT-3, suggesting a potential enhancement of mitophagy. Linagliptin demonstrated a positive impact on various factors related to kidney health in the context of CDDP-induced impairment. These findings suggest a potential role for linagliptin in improving cancer treatment outcomes. Clinical trials are warranted to further investigate and validate its efficacy in a clinical setting.

Aerobic exercise improves cognitive flexibility and modulates regional volume changes in a rat model of autism

Gestational exposure to valproic acid (VPA) is a risk factor for autism spectrum disorder (ASD). Rodents exposed to VPA in utero display common features of ASD, including volumetric dysregulation in higher-order cognitive regions like the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus. Exercise has been shown in elderly populations to boost cognition and to buffer against brain volume losses with age. This study employed an adolescent treadmill exercise intervention to facilitate cognitive flexibility and regional brain volume regulation in rats exposed to VPA during gestation. It was found that exercise improved performance on extra-dimensional shifts of attention on a set-shifting task, which is indicative of improved cognitive flexibility. Exercise decreased frontal cortex volume in females, whereas in males exercise increased the ventral hippocampus. These findings suggest that aerobic exercise may be an effective intervention to counteract the altered development of prefrontal and hippocampal regions often observed in ASD.

Chromium nanoparticles improve bone turnover regulation in rats fed a high-fat, low-fibre diet.

The aim of the study was to investigate the effect of returning to a balanced diet combined with chromium picolinate (CrPic) or chromium nanoparticles (CrNPs) supplementation at a pharmacologically relevant dose of 0.3 mg/kg body weight on the expression level of selected genes and bone turnover markers in the blood and bones of rats fed an obese diet. The results of the study showed that chronic intake of a high-fat obesogenic diet negatively affects bone turnover by impairing processes of both synthesis and degradation of bones. The switch to a healthy diet proved insufficient to regulate bone metabolism disorders induced by an obesogenic diet, even when it was supplemented with chromium, irrespective of its form. Supplementation with CrPic with no change in diet stimulated bone metabolism only at the molecular level, towards increased osteoclastogenesis (bone resorption). In contrast, CrNPs added to the high-fat diet effectively regulated bone turnover by increasing both osteoblastogenesis and osteoclastogenesis, with these changes directed more towards bone formation. The results of the study suggest that unfavourable changes in bone metabolism induced by chronic intake of a high-fat diet can be mitigated by supplementation with CrNPs, whereas a change in eating habits fails to achieve a similar effect.

High Intensity Interval Training can Ameliorate Hypothalamic Appetite Regulation in Male Rats with Type 2 Diabetes: The Role of Leptin.

Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling.In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups.The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001).The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement. Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1).

Physiological strategies in wild rodents: immune defenses of commensal rats.

The importance of issues associated with urban/commensal rats and mice (property damage, management costs, and health risks) press upon research on these animals. While the demography of commensal rodents is mostly studied, the need for understanding factors influencing their natural morbidity/mortality is also stressed. In this respect, more attention is expected to be paid to immunity, the physiological mechanism of defense against host survival threats (pathogens, parasites, diseases). Commensal rats and mice carry numerous pathogens that evoke diverse immune responses. The state of immunity in commensal house mice is studied in great detail, owing to the use of laboratory strains in biomedical research. Because commensal rats are, compared to mice, carriers of more zoonotic agents, rats' immunity is studied mainly in that context. Some of these zoonotic agents cause chronic, asymptomatic infections, which justified studies of immunological mechanisms of pathogen tolerance versus clearance regulation in rats. Occurrence of some infections in specific tissues/organs pressed upon analysis of local/regional immune responses and/or immunopathology. A survey of immunological activity/responses in commensal rats is given in this review, with mention of existing data in commensal mice. It should throw some light on the factors relevant to their morbidity and lifespan, supplementing the knowledge of commensal rodent ecology.

Piezo1 channel activation facilitates baroreflex afferent neurotransmission with subsequent blood pressure reduction in control and hypertension rats.

Mechanosensitive cation channels such as Piezo1 and Piezo2 are activated by mechanical force like a starched wall of the aorta while blood pressure (BP) rising, which helps to elucidate the underlying mechanism of mechanotransduction of baroreceptor endings. In this study we investigated how Piezo1 channel activation-mediated gender- and afferent-specific BP regulation in rats. We established high-fat diet and fructose drink-induced hypertension model rats (HFD-HTN) and deoxycorticosterone (DOCA)-sensitive hypertension model rats. We showed that the expression levels of Piezo1 and Piezo2 were significantly up-regulated in left ventricle of HFD and DOCA hypertensive rats, whereas the down-regulation of Piezo1 was likely to be compensated by Piezo2 up-regulation in the aorta. Likewise, down-regulated Piezo1 was observed in the nodose ganglion (NG), while up-regulated Piezo2 was found in the nucleus tractus solitarius (NTS), which might synergistically reduce the excitatory neurotransmitter release from the presynaptic membrane. Notably, microinjection of Yoda1 (0.025-2.5 mg/ml) into the NG concentration-dependently reduced BP in both hypertensive rat models as well as in control rats with similar EC50; the effect of Yoda1 was abolished by microinjection of a Piezo1 antagonist GsMTx4 (1.0 μM). Functional analysis in an in vitro aortic arch preparation showed that instantaneous firing frequency of single Ah-fiber of aortic depressor nerve was dramatically increased by Yoda1 (0.03-1.0 μM) and blocked by GsMTx4 (1.0 μM). Moreover, spontaneous synaptic currents recorded from identified 2nd-order Ah-type baroreceptive neurons in the NTS was also facilitated over 100% by Yoda1 (1.0 μM) and completely blocked by GsMTx4 (3.0 μM). These results demonstrate that Piezo1 expressed on Ah-type baroreceptor and baroreceptive neurons in the NG and NTS plays a key role in a sexual-dimorphic BP regulation under physiological and hypertensive condition through facilitation of baroreflex afferent neurotransmission, which is presumably collaborated by Piezo2 expression at different level of baroreflex afferent pathway via compensatory and synergistic mechanisms.

Optimal timing of free total rhubarb anthraquinones on immune regulation in rats with severe acute pancreatitis.

Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. FTRAs (22.5, 45 and 90mg/kg), Rhubarb (RHU) (900mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72h every 12h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. The results showed that administration of FTRAs at 0h was superior to 48h and 72h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48h of development, administration of FTRAs at the early stage (0h, immune overreaction period) was the optimal time and superior to that of 48h and 72h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.

Effect of DHA-Enriched Phospholipids from Fish Roe on Rat Fecal Metabolites: Untargeted Metabolomic Analysis.

Lipid metabolism disorder has become an important hidden danger threatening human health, and various supplements to treat lipid metabolism disorder have been studied. Our previous studies have shown that DHA-enriched phospholipids from large yellow croaker (Larimichthys Crocea) roe (LYCRPLs) have lipid-regulating effects. To better explain the effect of LYCRPLs on lipid regulation in rats, the fecal metabolites of rats were analyzed from the level of metabolomics in this study, and GC/MS metabolomics measurements were performed to figure out the effect of LYCRPLs on fecal metabolites in rats. Compared with the control (K) group, 101 metabolites were identified in the model (M) group. There were 54, 47, and 57 metabolites in the low-dose (GA), medium-dose (GB), and high-dose (GC) groups that were significantly different from that of group M, respectively. Eighteen potential biomarkers closely related to lipid metabolism were screened after intervention with different doses of LYCRPLs on rats, which were classified into several metabolic pathways in rats, including pyrimidine metabolism, the citric acid cycle (TCA cycle), the metabolism of L-cysteine, carnitine synthesis, pantothenate and CoA biosynthesis, glycolysis, and bile secretion. L-cysteine was speculated to be a useful biomarker of LYCRPLs acting on rat fecal metabolites. Our findings indicated that LYCRPLs may regulate lipid metabolism disorders in SD rats by activating these metabolic pathways.

Dose-Dependent Heart Rhythm Disturbance Occurring in Response to the Activation of Choline-Reactive Structures in Early Rat Ontogeny.

The effect of dose-dependent activation of cholinoreactive structures on the severity of sinus bradycardia occurring in some intact newborn rats during the first weeks after birth was analyzed in non-narcotized one-day-old (P1) and 16-day-old (P16) rats. The parameters of low-amplitude bradycardic oscillations of heart rhythm in norm and after administration of the acetylcholinesterase inhibitor physostigmine (eserine) in different doses (1/100, 1/10, and 3/4LD50) to rats were studied. The maximum increase in the power of low-amplitude brady-cardic oscillations was achieved during moderate activation of cholinoreactive structures after injection of eserine in a dose of 1/10LD50. Further increase in acetylcholine level led to disappearance of the sinus rhythm and development of pathological bradycardia. The data obtained indicate the immaturity of the mechanisms of heart rhythm regulation in rats immediately after birth. During activation of cholinoreactive structures, the severity of bradycardia oscillations increases exponentially at P1 and has an inverse exponential character at P16, which indicates a high risk of cardiac rhythmogenesis disorders and dysrhythmia development in newborn rats under conditions of excessive enhancement of cholinergic activation.

Activation of 5-HT3 receptors in the medulla oblongata is involved in the phasic control of urinary bladder

The control of micturition depends on reflex mechanisms, however, it undergoes modulation from cortex, pons and medullary areas. This study investigated if the activation of 5-HT3 receptors in the medulla influences the urinary bladder (UB) regulation in rats. Isoflurane female Wistar rats were submitted to catheterization of the femoral artery and vein for mean arterial pressure (MAP) and heart rate (HR) recordings and injection of drugs, respectively. The UB was cannulated for intravesical pressure (IP) measurement. The Doppler flow probe was placed around the left renal artery for renal conductance (RC) recordings. Phenylbiguanide (PB) and granisetron (GN) were injected into the 4th brain ventricle in rats with guide cannulas implanted 5 days prior to the experiments; or PB and GN were randomly injected intravenously or applied topically (in situ) on the UB. PB injection into 4th V significantly increased IP (68.67 ± 11.70%) and decreased MAP (−29 ± 6 mmHg) compared to saline (0.34 ± 0.64% and −2 ± 2 mmHg), with no changes in the HR and RC. GN injection into the 4th V did not significantly change the IP and RC compared to saline, nevertheless, significantly increased MAP (25 ± 4 mmHg) and heart rate (36 ± 9 bpm) compared to saline. Intravenous PB and GN only produced cardiovascular effects, whilst PB but not GN in situ on the UB evoked increase in IP (111.60 ± 30.36%). Therefore, the activation of 5HT-3 receptors in medullary areas increases the intravesical pressure and these receptors are involved in the phasic control of UB. In contrast, 5-HT3 receptors in the medulla oblongata are involved in the pathways of the tonic control of the cardiovascular system. The activation of 5-HT3 receptors in the bladder cause increase in intravesical pressure and this regulation seem to be under phasic control as the blockade of such receptors elicits no changes in baseline intravesical pressure.

Decrease in the rewarding value of spatial novelty due to the contamination of the stimulus field with light – Evidence from a free exploration test involving rats

It has been shown that rearranging the spatial properties of a familiar environment consistently elicits a positive response in rats directed toward the source of novelty. Previous studies have been conducted under red light or darkness. The purpose of this study was to test the effect of rearranging the spatial properties of a familiar environment in conjunction with a change in lighting conditions. The results have shown specific effects of the light presence and its intensity on different behavioral measures. We propose that this study provides a basis for hypothesizing a two-way mechanism of the behavioral response to light regulation in rats. The first is based on ON/OFF states. This level may be related to fundamental, evolutionarily early, emergent components of behavioral antipredator adaptations. Another level of behavioral regulation involves mechanisms sensitive to light intensity. These appear to be involved in the regulation of more advanced behavioral acts, such as exploratory responses. This may suggest that light intensity analysis may require the involvement of more advanced cognitive components in the behavioral regulation system.

Activation of the Ventrolateral Preoptic Neurons Projecting to the Perifornical-Hypothalamic Area Promotes Sleep: DREADD Activation in Wild-Type Rats.

The ventrolateral preoptic area (VLPO) predominantly contains sleep-active neurons and is involved in sleep regulation. The perifornical-hypothalamic area (PF-HA) is a wake-regulatory region and predominantly contains wake-active neurons. VLPO GABAergic/galaninergic neurons project to the PF-HA. Previously, the specific contribution of VLPO neurons projecting to the PF-HA (VLPO > PF-HAPRJ) in sleep regulation in rats could not be investigated due to the lack of tools that could selectively target these neurons. We determined the contribution of VLPO > PF-HAPRJ neurons in sleep regulation by selectively activating them using designer receptors exclusively activated by designer drugs (DREADDs) in wild-type Fischer-344 rats. We used a combination of two viral vectors to retrogradely deliver the Cre-recombinase gene, specifically, in VLPO > PF-HA neurons, and further express hM3Dq in those neurons to selectively activate them for delineating their specific contributions to sleep–wake functions. Compared to the control, in DREADD rats, clozapine-N-oxide (CNO) significantly increased fos-expression, a marker of neuronal activation, in VLPO > PF-HAPRJ neurons (2% vs. 20%, p < 0.01) during the dark phase. CNO treatment also increased nonREM sleep (27% vs. 40%, p < 0.01) during the first 3 h of the dark phase, when rats are typically awake, and after exposure to the novel environment (55% vs. 65%; p < 0.01), which induces acute arousal during the light phase. These results support a hypothesis that VLPO > PF-HAPRJ neurons constitute a critical component of the hypothalamic sleep–wake regulatory circuitry and promote sleep by suppressing wake-active PF-HA neurons.

Effect of estrogen application timing on adipose tissue revascularization and immune regulation in rats after autologous fat transplantation

Purpose: To study the effect of timing of estrogen application on adipose tissue revascularization and immune regulation in rats given autologous fat transplantation.Methods: Ninety (90) healthy rats were selected for use in this study. The rats were randomly divided into a study group (n = 45) and control group (n = 45). After ovariectomy, the study group was given estrogen replacement therapy before autologous fat transplantation, while the control group was given estrogen replacement therapy after autologous fat transplantation. The rats were observed for 6 weeks after transplantation. Micro-vessel density, wet weight of transplanted fat, VEGF expression level, levels of M1 and M2 in macrophages, and macrophage infiltration rate were determined 40 days postautologous fat transplantation.Results: Forty days after autologous fat transplantation, microvessel density, wet weight of transplanted fat, expression level of VEGF and levels of M1 and M2 in macrophages were significantly higher in study group rats than in controls (p &lt; 0.05). There was 80 % macrophage infiltration in the study group rats, while the corresponding control value (61 %) was significantly lower (p &lt; 0.05).Conclusion: Estrogen treatment before autologous fat transplantation in rats is helpful for the revascularization of adipose tissue, enhances vascular regeneration, promotes the survival of adipose tissue after transplantation, and activates immune cells. It also promotes the production of immune factors, and improves immunoregulation in adipose tissue. Thus, this therapeutic strategy may be useful in clinical practice, but further clinical trials are required.

ALTERATION OF RENAL DOPAMINERGIC SYSTEM IN RATS FED WITH HIGH FAT DIET: A POSSIBLE MECHANISM PROMOTING ARTERIAL HYPERTENSION

Objective: A chronic high fat diet (HFD) induces insulin resistance and enhances renal sodium reabsorption. The renal dopaminergic system (RDS) is a local natriuretic system involved in blood pressure regulation. We analyzed the effect of a HFD on the RDS and its impact on blood pressure regulation in rats. Design and method: Six weeks old male Sprague-Dawley rats were divided into two groups (n = 4–6), and studied for 4, 8 and 12 weeks. C (Control): standard diet (SD) and tap water to drink; HFD: 50% w/w bovine fat added to SD and tap water to drink. We determined: Systolic blood pressure (SBP); urine excretion of L-dopa and dopamine by HPLC (L-dopa/dopamine index was calculated); plasmatic, urinary biochemical, and kidney function parameters; and organic cation transporter N1, 2 and 3 (OCT-N1/2/3) protein expression in renal cortex tissue by western blot. Results: SBP (mmHg): HFD4: 134 ± 2 vs. C4: 120 ± 2; HFD8: 135 ± 2 vs. C8: 121 ± 2; HFD12: 147 ± 2 vs. C12 115 ± 3; p &lt; 0.01. fractional sodium excretion (FENa, %): HFD4: 0.19 ± 0.03 vs. C4: 0.63 ± 0.04; HFD8: 0.18 ± 0.02 vs. C8: 0.49 ± 0.06; HFD12: 0.05 ± 0.02 vs. C12 0.35 ± 0.05; p &lt; 0.01. urinary sodium excretion (UNa.V, mEq/24hs): HFD4: 0.53 ± 0.05 vs. C4: 2.09 ± 0.15; HFD8: 0.51 ± 0.07 vs. C8: 1.94 ± 0.11; HFD12: 0.16 ± 0.04 vs. C12: 0.97 ± 0.17, p &lt; 0.01. Daily diuresis (ml/24hs): HFD4: 3.6 ± 0,7 vs. C4: 13.5 ± 1.3; HFD8: 3.5 ± 0.3 vs. C8: 16.4 ± 2.2; HFD12: 4.3 ± 0.7 vs. C12: 15.3 ± 1.6, p &lt; 0,0001. L-dopa/dopamine index: HFD4: 3.6 ± 0.3 vs. C4: 1.1 ± 0.2, p &lt; 0.005; HFD8: 3.7 ± 0.7 vs. C8: 1.1 ± 0.2, p &lt; 0.05; HFD12: 4.8 ± 0.2 vs. C12: 2.0 ± 0.3, p &lt; 0.01. A positive correlation between SBP vs the L-dopa/dopamine index: p &lt; 0.001, r = 0.985, R2 = 0.97; and a negative correlation between UNa.V vs L-dopa/dopamine index: p &lt; 0.001, r = -0.959, R2 = 0.92 were found. Expression of transporter OCT-N1/2/3 / GAPDH were: HFD8: 0.6 ± 0.1 vs. C8: 1.0 ± 0.2, p &lt; 0.05. Conclusions: The reduction in natriuresis could be related to the decrease in dopamine excretion to the proximal convoluted tubular lumen caused by the reduced expression of OCT-N1/2/3 transporters, contributing to increase blood pressure.

Characterization of Acidic Tea Polysaccharides from Yellow Leaves of Wuyi Rock Tea and Their Hypoglycemic Activity via Intestinal Flora Regulation in Rats.

A bioactive acidic tea polysaccharide from yellow leaves of Wuyi rock tea was successively prepared via DEAE-52 and Superdex-200 columns. Nuclear magnetic resonance (NMR) analysis showed that the main glycosidic bonds were composed of α-l-Araf-(1→, →5)-α-l-Araf-(1→, →4)-α-d-Glcp-(1→, Arap-(1→, →6)-α-d-Glcp-(1→, →2,4)-α-l-Rhap-(1→, →3,4)-α-d-Glcp-(1→, →4)-α-d-GalAp-(1→, →4)-α-d-GalAp-(1→, α-d-Galp-(1→, →6)-β-d-Galp-(1→ and →4)-β-d-Galp-(1→. The molecular weight was 3.9285 × 104 Da. The hypoglycemic effect of acidic tea polysaccharides on streptozotocin-induced type 2 diabetes mellitus rats was evaluated through histopathology and biochemistry analysis. The acidic tea polysaccharide could improve plasma and liver lipid metabolism. Moreover, 16S rRNA gene sequencing revealed that the composition of the intestinal flora changed drastically after treatment, namely, blooms of Bifidobacterium, Blautia, Dorea, and Oscillospira, and a strong reduction in Desulfovibrio and Lactobacillus. The above results illustrated that tea polysaccharides might serve as an effective ingredient to ameliorate glucose metabolism disorders and intestinal flora in hyperglycemic rats.

Estrogen-dependent depressor response of melatonin via baroreflex afferent function and intensification of PKC-mediated Nav1.9 activation.

Recent studies suggest that melatonin (Mel) plays an important role in the regulation of blood pressure (BP) via the aortic baroreflex pathway. In this study, we investigated the interaction between the baroreflex afferent pathway and Mel-mediated BP regulation in rats under physiological and hypertensive conditions. Mel (0.1, 0.3, and 1.0 mg/mL) was microinjected into the nodose ganglia (NG) of rats. We showed that Mel-induced reduction of mean arterial pressure in female rats was significantly greater than that in male and in ovariectomized rats under physiological condition. Consistently, the expression of Mel receptors (MTNRs) in the NG of female rats was significantly higher than that of males. In L-NAME-induced hypertensive and spontaneously hypertensive rat models, MTNRs were upregulated in males but downregulated in female models. Interestingly, Mel-induced BP reduction was found in male hypertensive models. In whole-cell recording from identified baroreceptor neurons (BRNs) in female rats, we found that Mel (0.1 μM) significantly increased the excitability of a female-specific subpopulation of Ah-type BRNs by increasing the Nav1.9 current density via a PKC-mediated pathway. Similar results were observed in baroreceptive neurons of the nucleus tractus solitarius, showing the facilitation of spontaneous and evoked excitatory post-synaptic currents in Ah-type neurons. Collectively, this study reveals the estrogen-dependent effect of Mel/MTNRs under physiological and hypertensive conditions is mainly mediated by Ah-type BRNs, which may provide new theoretical basis and strategies for the gender-specific anti-hypertensive treatment in clinical practice.

Effects of specific nutritional components and supplementing obesogenic diet with quinoa on body weight regulation in rats

Rationale: The cafeteria diet is a robust model of diet induced obesity and consists of highly energetic and highly palatable human foods to trigger diet induced obesity in rats. Quinoa (Chenopodium quinoa) is a pseudo-cereal containing healthy nutritional constituents like indispensable amino acids, minerals and dietary fiber. This study aimed to evaluate the potential preventive effect of quinoa on body weight and energy intake in rats consumed cafeteria diet supplemented with quinoa.

Transcriptome Profiling of Duodenum Reveals the Importance of Boron Supplementation in Modulating Immune Activities in Rats.

As an essential trace element, appropriate boron supplementation can promote immune function of animals. To illustrate the effects of boron in a rat model, RNA-Seq was conducted for the RNA from duodenum after treatment with different concentration of boron in which boron was given in the form of boric acid. More than 47 million reads were obtained in 0, 10, and 320mg/L boron (0, 57.21, and 1830.66mg/L boric acid) treatment groups that produced 58 965 402, 48 607 328, and 46 760 660 clean reads, respectively. More than 95% of the clean reads were successfully matched to the rat reference genome and assembled to generate 32 662 transcripts. A total of 624 and 391 differentially expressed candidate genes (DEGs) were found between 0 vs.10 and 0 vs. 320mg/L boron comparison groups. We also identified transcription start site, transcription terminal site, and skipped exons as the main alternative splicing events. GO annotations revealed most of DEGs were involved in the regulation of immune activity. The DEGs were enriched in influenza A, herpes simplex infection, cytosolic DNA-sensing pathway, and antigen processing and presentation signaling pathways. The expression levels of genes enriched in these signaling pathways indicate that lower doses of boron could achieve better effects on promoting immune response in the duodenum. These effects on the immune system appear to be mediated via altering the expression patterns of genes involved in the related signaling pathways in a dose-dependent pattern. These data provide more insights into the molecular mechanisms of immune regulation in rats in response to dietary boron treatment.