scholarly journals Sites and sources of sympathoexcitation in obese male rats: role of brain insulin

2020 ◽  
Vol 318 (3) ◽  
pp. R634-R648 ◽  
Author(s):  
Zhigang Shi ◽  
Ding Zhao ◽  
Priscila A. Cassaglia ◽  
Virginia L. Brooks
Keyword(s):  
Insulin Receptors ◽  
Male Rats ◽  
Melanocortin Receptor ◽  
Sprague Dawley ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Y1 Receptors ◽  
The Brain ◽  
Obese Male

In males, obesity increases sympathetic nerve activity (SNA), but the mechanisms are unclear. Here, we investigate insulin, via an action in the arcuate nucleus (ArcN), and downstream neuropathways, including melanocortin receptor 3/4 (MC3/4R) in the hypothalamic paraventricular nucleus (PVN) and dorsal medial hypothalamus (DMH). We studied conscious and α-chloralose-anesthetized Sprague-Dawley rats fed a high-fat diet, which causes obesity prone (OP) rats to accrue excess fat and obesity-resistant (OR) rats to maintain fat content, similar to rats fed a standard control (CON) diet. Nonspecific blockade of the ArcN with muscimol and specific blockade of ArcN insulin receptors (InsR) decreased lumbar SNA (LSNA), heart rate (HR), and mean arterial pressure (MAP) in OP, but not OR or CON, rats, indicating that insulin supports LSNA in obese males. In conscious rats, intracerebroventricular infusion of insulin increased MAP only in OP rats and also improved HR baroreflex function from subnormal to supranormal. The brain sensitization to insulin may elucidate how insulin can drive central SNA pathways when transport of insulin across the blood-brain barrier may be impaired. Blockade of PVN, but not DMH, MC3/4R with SHU9119 decreased LSNA, HR, and, MAP in OP, but not OR or CON, rats. Interestingly, nanoinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased LSNA only in OP rats, similar to PVN MTII-induced increases in LSNA in CON rats after blockade of sympathoinhibitory neuropeptide Y Y1 receptors. ArcN InsR expression was not increased in OP rats. Collectively, these data indicate that obesity increases SNA, in part via increased InsR signaling and downstream PVN MC3/4R.

Albumin is not an irreplaceable carrier for amphipathic mediators of thermoregulatory responses to LPS: compensatory role of α1-acid glycoprotein

2005 ◽  
Vol 288 (4) ◽  
pp. R872-R878 ◽  
Author(s):  
Andrei I. Ivanov ◽  
Alexandre A. Steiner ◽  
Shreya Patel ◽  
Alla Y. Rudaya ◽  
Andrej A. Romanovsky
Keyword(s):  
Inflammatory Mediators ◽  
Platelet Activating Factor ◽  
Prostaglandin E ◽  
High Dose ◽  
Sprague Dawley ◽  
Acid Glycoprotein ◽  
Sprague Dawley Rats ◽  
Lps Signaling ◽  
The Brain

In view of the potential involvement of peripherally synthesized, circulating amphipathic mediators [such as platelet-activating factor (PAF) and prostaglandin E2] in the systemic inflammatory response to lipopolysaccharide (LPS), we hypothesized that transport of amphipaths by albumin is essential for conveying peripheral inflammatory signals to the brain. Our first specific aim was to test this hypothesis by studying LPS-induced fever and hypothermia in Nagase analbuminemic rats (NAR). NAR from two different colonies and normalbuminemic Sprague-Dawley rats were preimplanted with jugular catheters, and their febrile responses to a mild dose of LPS (10 μg/kg iv) at thermoneutrality and hypothermic responses to a high dose of LPS (500 μg/kg iv) in the cold were studied. NAR of both colonies developed normal febrile and hypothermic responses, thus suggesting that transport of amphipathic mediators by albumin is not indispensable for LPS signaling. Although alternative carrier proteins [such as α1-acid glycoprotein (AGP)] are known to assume transport functions of albumin in NAR, it is unknown whether inflammatory mediators are capable of inducing their actions when bound to alternative carriers. To test whether PAF, the most potent amphipathic pyrogen, causes fever when administered in an AGP-bound form was our second aim. Sprague-Dawley rats were preimplanted with jugular catheters, and their thermal responses to infusion of a 1:1 [PAF-AGP] complex (40 nmol/kg iv), AGP (40 nmol/kg iv), or various doses of free (aggregated) PAF were studied. The complex, but neither free PAF nor AGP, caused a high (∼1.5°C) fever with a short (<10 min) latency. This is the first demonstration of a pyrogenic activity of AGP-bound PAF. We conclude that, in the absence of albumin, AGP and possibly other carriers participate in immune-to-brain signaling by binding and transporting amphipathic inflammatory mediators.

Metalloendopeptidases EC 3.4.24.15/16 regulate bradykinin activity in the cerebral microvasculature

2003 ◽  
Vol 284 (6) ◽  
pp. H1942-H1948 ◽  
Author(s):  
M. Ursula Norman ◽  
Rebecca A. Lew ◽  
A. Ian Smith ◽  
Michael J. Hickey
Keyword(s):  
Specific Inhibitor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cerebral Microvasculature ◽  
Microvessel Permeability ◽  
The Brain ◽  
Cerebral Microvessel

Bradykinin is a vasoactive peptide that has been shown to increase the permeability of the cerebral microvasculature to blood-borne macromolecules. The two zinc metalloendopeptidases EC 3.4.24.15 (EP 24.15) and EC 3.4.24.16 (EP 24.16) degrade bradykinin in vitro and are highly expressed in the brain. However, the role that these enzymes play in bradykinin metabolism in vivo remains unclear. In the present study, we investigated the role of EP 24.15 and EP 24.16 in the regulation of bradykinin-induced alterations in microvascular permeability. Permeability of the cerebral microvasculature was assessed in anesthetized Sprague-Dawley rats by measuring the clearance of 70-kDa FITC dextran from the brain. Inhibition of EP 24.15 and EP 24.16 by the specific inhibitor N-[1-( R, S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr- p-aminobenzoate (JA-2) resulted in the potentiation of bradykinin-induced increases in cerebral microvessel permeability. The level of potentiation was comparable to that achieved by the inhibition of angiotensin-converting enzyme. These findings provide the first evidence of an in vivo role for EP 24.15/EP 24.16 in brain function, specifically in regulating alterations in microvessel permeability induced by exogenous bradykinin.

Effect of central amiloride infusion on mineralocorticoid hypertension

1994 ◽  
Vol 267 (5) ◽  
pp. E754-E758 ◽  
Author(s):  
E. P. Gomez-Sanchez ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Na Channel ◽  
Sprague Dawley ◽  
Cellular Mechanisms ◽  
Subcutaneous Infusion ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Different Types ◽  
The Brain

There is strong evidence from different types of studies, including the discrete infusion of agonists and antagonists and ablation of specific brain areas or transmitter-type neurons, that mineralocorticoids, in excess, act in the brain to elevate blood pressure. Aldosterone enhances the entry of Na+ through amiloride-sensitive Na+ channels in some mineralocorticoid-sensitive transport epithelial cells. To define possible cellular mechanisms involved in central mineralocorticoid action, benzamil, an amiloride analogue with selective affinity for the Na+ channel, was continuously infused intracerebroventricularly in three mineralocorticoid-dependent hypertension models in Sprague-Dawley rats, the continuous subcutaneous infusion of aldosterone, the intracerebroventricular infusion of aldosterone, and the ingestion of carbenoxolone, a synthetic licorice analogue. The intracerebroventricular infusion of 0.3 and 0.5 micrograms/h of benzamil, doses that did not have an adverse effect on growth and that had no effect on the blood pressure when infused subcutaneously, prevented the increase in blood pressure in these models. The infusion of these levels of benzamil had no effect on urine volume even in those animals in which it prevented an increase in blood pressure. These data suggest that the central effects of mineralocorticoids on blood pressure are mediated, at least in part, by the effects of mineralocorticoids on amiloride-sensitive sodium transport.

scholarly journals A Long-Term Energy-Rich Diet Increases Prefrontal BDNF in Sprague-Dawley Rats

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 126
Author(s):  
Alessandro Virtuoso ◽  
Pernille Tveden-Nyborg ◽  
Anne Marie Voigt Schou-Pedersen ◽  
Jens Lykkesfeldt ◽  
Heidi Kaastrup Müller ◽  
...  
Keyword(s):  
Dehydroascorbic Acid ◽  
Male Rats ◽  
Human Consumption ◽  
Sprague Dawley ◽  
Monoamine Neurotransmitters ◽  
Redox Imbalance ◽  
Sprague Dawley Rats ◽  
Negative Effect ◽  
Term Energy ◽  
The Brain

Findings of the effect of high-fat feeding including “Cafeteria Diets” (CAF) on brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and prefrontal cortex (PFC) in rodents are conflicting. CAF is a non-standardized, highly palatable energy-rich diet composed by everyday food items for human consumption and is known to induce metabolic syndrome and obesity in rats. However, the highly palatable nature of CAF may counteract a negative effect of chronic stress on anticipatory behavior and synaptic plasticity in the hippocampus, hence represent a confounding factor (e.g., when evaluating functional effects on the brain). This study investigated the effects of a chronic, restricted access to CAF on BDNF, monoamine neurotransmitters, and redox imbalance in HIP and PFC in male rats. Our results show that CAF induced BDNF and its receptor TrkB in PFC compared to the controls (p < 0.0005). No differences in monoamine neurotransmitters were detected in either PFC or HIP. CAF increased dehydroascorbic acid and decreased malondialdehyde in PFC (p < 0.05), suggesting an early redox imbalance insufficient to induce lipid peroxidation. This study supports that a chronic CAF on a restricted schedule increases BDNF levels in the PFC of rats, highlighting that this may be a suboptimal feeding regime when investigating the effects of diet-induced obesity in the brain and emphasizing this as a point of attention when comparing the findings.

scholarly journals 20-HETE and CYP4A2 ω-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats

2016 ◽  
Vol 311 (1) ◽  
pp. F71-F77 ◽  
Author(s):  
Carolina Dalmasso ◽  
Rodrigo Maranon ◽  
Chetan Patil ◽  
Mohadetheh Moulana ◽  
Damian G. Romero ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Hydroxylase Activity ◽  
Sprague Dawley Rats ◽  
Low Salt ◽  
Cytochrome P 450

In male rats, androgen supplements increase 20-hydroxyeicosatetraenoic acid (20-HETE) via cytochrome P-450 (CYP)4A ω-hydroxylase and cause an increase in blood pressure (BP). In the present study, we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague-Dawley rats (96 ± 2 vs. 108 ± 2 mmHg, P < 0.05) and was associated with increased renal microvascular CYP4A2 mRNA expression (15-fold), endogenous renal 20-HETE (5-fold), and ω-hydroxylase activity (3-fold). Chronic DHT also increased MAP in low salt-fed Dahl salt-resistant female rats (81 ± 4 vs. 95 ± 1 mmHg, P < 0.05) but had no effect on MAP in Dahl salt-sensitive female rats (154 ± 3 vs. 153 ± 3 mmHg), which are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2−/− and SS.5Bn (wild type) rats were treated with DHT. DHT increased MAP in SS.5Bn female rats (104 ± 1 vs. 128 ± 1 mmHg, P < 0.05) but had no effect in CYP4A2−/− female rats (118 ± 1 vs. 120 ± 1 mmHg). Renal microvascular 20-HETE was reduced in control CYP4A2−/− female rats and was increased with DHT in SS.5Bn female rats (6-fold) but not CYP4A2−/− female rats. ω-Hydroxylase activity was 40% lower in control CYP4A2−/− female rats than in SS.5Bn female rats, and DHT decreased ω-hydroxylase activity in SS.5Bn female rats (by 50%) but significantly increased ω-hydroxylase activity in CYP4A2−/− female rats (3-fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic female rats. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome.

Duodenal loading with glucose induces Fos expression in rat brain: selective blockade by devazepide

1999 ◽  
Vol 277 (3) ◽  
pp. R667-R674 ◽  
Author(s):  
Lixin Wang ◽  
Sylvain Cardin ◽  
Vicente Martínez ◽  
Yvette Taché ◽  
K. C. Kent Lloyd
Keyword(s):  
Area Postrema ◽  
Central Nucleus ◽  
Intestinal Lumen ◽  
Sprague Dawley ◽  
Selective Blockade ◽  
Lateral Parabrachial Nucleus ◽  
Sprague Dawley Rats ◽  
Fos Expression ◽  
The Brain

The role of CCK in mediating neuronal activity in the brain in response to dietary carbohydrate was measured by detecting Fos immunoreactivity in response to duodenal glucose load in rats after administration of the CCK-A receptor antagonist devazepide. In adult, male Sprague-Dawley rats, infusion for 30 min of 545 mg (2.18 kcal) dextrose through a duodenal cannula induced Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), lateral division of the central nucleus of the amygdala (CeAL), and the external subnucleus of the lateral parabrachial nucleus (LPBE). Devazepide treatment (1 mg/kg) attenuated Fos expression in the NTS and AP by 81 and 78%, respectively, but not in the CeAL or LPBE. These results indicate that central neuronal activation is elicited by dietary glucose in the intestinal lumen and that activation of neurons in the NTS and AP is mediated by CCK-A receptors.

scholarly journals Effects of Intestinal Microbiota on Pharmacokinetics of Crocin and Crocetin in Male Sprague-Dawley Rats

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 424
Author(s):  
Rajina Shakya ◽  
Mahesh R. Nepal ◽  
Mi Jeong Kang ◽  
Tae Cheon Jeong
Keyword(s):  
Intestinal Microbiota ◽  
Oral Treatment ◽  
Hepatic Metabolism ◽  
Crocus Sativus ◽  
Male Rats ◽  
Sprague Dawley ◽  
Gardenia Jasminoides ◽  
Sprague Dawley Rats

In addition to the hepatic metabolism, the role of intestinal microbiota in drug metabolism has been considered important in the biotransformation of xenobiotics. Crocin and its aglycone, crocetin, isolated from many plants, including the dried stigma of Crocus sativus and the fruit of Gardenia jasminoides, have been used in treatment of inflammation, cancer, and metabolic disorders. In this study, the effect of intestinal microbiota on the pharmacokinetics of crocin was studied following single oral treatment with 600 mg/kg crocin to male rats pre-treated with a mixture of antibiotics, such as cefadroxil, oxytetracycline, and erythromycin, for three consecutive days. Following crocin treatment, blood, urine, and feces were collected at various time points for evaluating pharmacokinetic characteristics of crocin and crocetin by using LC-MS. Results showed that intestinal absorption of crocin was relatively marginal when compared with that of crocetin, and that crocin metabolism to crocetin by intestinal microbiota would be a critical step for absorption. The present results clearly suggested that the in vivo pharmacological effects of crocin might be considered as the effects by its aglycone, crocetin, mainly, and that the metabolism of glycosidic natural products by intestinal microbiota should be considered to understand their pharmacodynamic actions.

Role of endogenous central opioid mechanisms in maintenance of body sodium balance

1995 ◽  
Vol 268 (3) ◽  
pp. R723-R730 ◽  
Author(s):  
D. R. Kapusta ◽  
J. C. Obih
Keyword(s):  
Sodium Intake ◽  
Dietary Sodium ◽  
Opioid Antagonist ◽  
Sodium Balance ◽  
Sodium Restriction ◽  
Sprague Dawley ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Body Sodium

The role of endogenous central opioids in the regulation of renal function was studied in Sprague-Dawley rats. In metabolism studies, changes in sodium balance were examined during normal dietary sodium intake (days 1-7; Na+ of 174 meq/kg) and sodium restriction (days 8-14; Na+ of 4.0 meq/kg). The influence of endogenous central opioids was investigated by repeating the protocol in the same rats during intracerebroventricular infusion of the opioid antagonist naltrexone methylbromide (NMBR). Intracerebroventricular NMBR did not alter sodium balance in rats fed normal sodium chow. In contrast, on low-sodium days 8 and 9, rats exhibited a more negative sodium balance during intracerebroventricular NMBR (day 8; -1,191 +/- 37 mu eq) compared with respective predrug control levels (day 8; -641 +/- 39 mu eq). Subcutaneous NMBR did not alter renal adaptation to sodium restriction. Thus central opioids are not involved in the maintenance of sodium balance during normal sodium intake. However, when dietary sodium is restricted, central opioid pathways are activated as a mechanism to maximally retain sodium.

scholarly journals Protective Effects of Fluvastatin on Reproductive Function in Obese Male Rats Induced by High-Fat Diet through Enhanced Signaling of mTOR

2017 ◽  
Vol 41 (2) ◽  
pp. 598-608 ◽  
Author(s):  
Xiangrong Cui ◽  
Chunlan Long ◽  
Jing Zhu ◽  
Jie Tian
Keyword(s):  
High Fat Diet ◽  
Reproductive Function ◽  
Male Rats ◽  
Control Group ◽  
Standard Diet ◽  
Protective Effects ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
Obese Male

Background: Statins can reduce reproductive damage induced by obesity or high-fat diet (HFD), but the specific regulatory mechanisms are largely unknown. Since mTOR/p70s6k sinaling promotes spermatogonia proliferation and spermatogenesis, we hypothesized that this pathway will be involved in the protective effects of statin in HFD-induced reproductive dysfunction. Methods: Male Sprague Dawley rats (3 weeks old) were randomly divided into a control group (standard diet), HFD group, and a fluvastatin group (HFD + fluvastatin at 6mg/kg, once daily by oral gavage). After 8 weeks, body weight was obtain and rats were sacrificed. Weights of the testes, gross morphology, sperm parameters, circulating levels of sex hormones, lipid levels, and tissue mTOR, p-P70s6k were measured. Another set of male rats were treated with rapamycin or vehicle. Flow cytometry was used to detect the spermatogonia marker c-kit and cell cycle. p-P70s6k expression was analyzed by Western blot. Results: HFD not only results in rat obesity but also leads to spermatogenetic damage and fluvastatin was able to partially block the effects of HFD. Fluvastatin also partially reversed the suppression of mTOR and p-p70s6k expresson. Conclusion: Our data suggest that fluvastatin has protective effects on reproductive function in obese male rats most probably through enhanced signaling of mTOR.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

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.

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