scholarly journals Regulation of cerebral arterial BKCa channels by angiotensin II signaling in adult offspring exposed to prenatal high sucrose diets

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xiuxia Gu ◽  
Axin He ◽  
Xiaorong Fan ◽  
Ruixiu Shi ◽  
Xueqin Feng ◽  
...  

Prenatal insults have been shown to affect vascular functions, leading to increased risks of cardiovascular diseases in offspring. The present study determined whether high sucrose (HS) intake in pregnancy affected central vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley rats were fed a standard food and tap water with normal or high (20%) sucrose content during pregnancy. Offspring were maintained with normal diets and tap water. Central vascular functions and related ion channels were assessed in male offspring at 5 months old. Compared with the control, angiotensin II (AII)-induced vasoconstrictions were significantly higher in the MCA of the offspring exposed to prenatal HS. In the MCA, large conductance Ca2+-activated K+ channels (BKCa) currents were decreased with a reduction of opening frequency, sensitivity to intracellular Ca2+/membrane voltage, and BKβ1 expression. mRNA levels of AT1α and AT2, as well as AT1/AT2 ratio, were significantly increased in the MCA of offspring following exposure to prenatal HS diets. The data suggested that prenatal HS diets could alter microvascular activities in the MCA, probably via changes of BKCa channels in the brain.

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Minoru Watanabe ◽  
Naoki Matsumoto ◽  
Yuko Takeba ◽  
Toshio Kumai ◽  
Masami Tanaka ◽  
...  

We investigated the effects of orange juice (OJ) or hesperidin, a component of OJ, on the pharmacokinetics of pravastatin (PRV) and the expression of both protein and mRNA of multidrug resistance-associated protein 2 (Mrp2) in the rat small intestine and liver. Eight-week-old male Sprague-Dawley rats were used in this study. OJ or a 0.079% hesperidin suspension was administered orally for 2 days. Tap water was given as a control. A single dose of PRV at 100 mg/kg p.o. was administered after 2 days of OJ, hesperidin, or tap water ingestion. The AUC, , andt1/2values of PRV were significantly increased in OJ group. Mrp2 protein and mRNA levels in the small intestine and liver, respectively, were significantly decreased after the ingestion of OJ. The same results were obtained with hesperidin. These results suggest that the changes in PRV pharmacokinetic parameters and the decrease in Mrp2 expression caused by OJ are due to hesperidin in the juice.


2020 ◽  
Vol 21 (20) ◽  
pp. 7750
Author(s):  
Anna Maria Czarnecka ◽  
Krzysztof Milewski ◽  
Jan Albrecht ◽  
Magdalena Zielińska

Acute liver failure (ALF) leads to neurological symptoms defined as hepatic encephalopathy (HE). Although accumulation of ammonia and neuroinflammation are generally accepted as main contributors to HE pathomechanism, a buildup of bile acids (BA) in the blood is a frequent component of liver injury in HE patients. Recent studies have identified the nuclear farnesoid X receptor (FXR) acting via small heterodimer partner (SHP) as a mediator of BA-induced effects in the brain of ALF animals. The present study investigated the status of the BA–FXR axis in the brain and the liver, including selective changes in pertinent genes in thioacetamide (TAA)-induced ALF in Sprague–Dawley rats. FXR was found in rat neurons, confirming earlier reports for mouse and human brain. BA accumulated in blood but not in the brain tissue. Expression of mRNAs coding for Fxr and Shp was reduced in the hippocampus and of Fxr mRNA also in the cerebellum. Changes in Fxr mRNA levels were not followed by changes in FXR protein. The results leave open the possibility that mobilization of the BA–FXR axis in the brain may not be necessarily pathognomonic to HE but may depend upon ALF-related confounding factors.


Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.


Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4329-4335 ◽  
Author(s):  
Edith Sánchez ◽  
Praful S. Singru ◽  
Runa Acharya ◽  
Monica Bodria ◽  
Csaba Fekete ◽  
...  

To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 ± 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.


2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.


2003 ◽  
Vol 285 (2) ◽  
pp. R420-R428 ◽  
Author(s):  
Andrej A. Romanovsky ◽  
Naotoshi Sugimoto ◽  
Christopher T. Simons ◽  
William S. Hunter

The organum vasculosum laminae terminalis (OVLT) has been proposed to serve as the interface for blood-to-brain febrigenic signaling, because ablation of this structure affects the febrile response. However, lesioning the OVLT causes many “side effects” not fully accounted for in the fever literature. By placing OVLT-lesioned rats on intensive rehydration therapy, we attempted to prevent these side effects and to evaluate the febrile response in their absence. After the OVLT of Sprague-Dawley rats was lesioned electrolytically, the rats were given access to 5% sucrose for 1 wk to stimulate drinking. Sucrose consumption and body mass were monitored. The animals were examined twice a day for signs of dehydration and treated with isotonic saline (50 ml/kg sc) when indicated. This protocol eliminated mortality but not several acute and chronic side effects stemming from the lesion. The acute effects included adipsia and gross (14% of body weight) emaciation; chronic effects included hypernatremia, hyperosmolality, a suppressed drinking response to hypertonic saline, and previously unrecognized marked (by ∼2°C) and long-lasting (>3 wk) hyperthermia. Because the hyperthermia was not accompanied by tail skin vasoconstriction, it likely reflected increased thermogenesis. After the rats recovered from the acute (but not chronic) side effects, their febrile response to IL-1β (500 ng/kg iv) was tested. The sham-operated rats developed typical monophasic fevers (∼0.5°C), the lesioned rats did not. However, the absence of the febrile response in the OVLT-lesioned rats likely resulted from the untreatable side effects. For example, hyperthermia at the time of pyrogen injection was high enough (39–40°C) to solely prevent fever from developing. Hence, the changed febrile responsiveness of OVLT-lesioned animals is given an alternative interpretation, unrelated to febrigenic signaling to the brain.


2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.


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