Gastric leptin: a novel role in cardiovascular regulation

Gastric-derived leptin affects satiety and gastrointestinal function via vagal mechanisms and has been shown to interact with the gut hormone cholecystokinin (CCK). CCK selectively inhibits splanchnic sympathetic nerve discharge (SND) and the activity of a subset of presympathetic vasomotor neurons in the rostroventrolateral medulla (RVLM). The present study sought to examine the effects of gastric leptin on arterial pressure (AP), heart rate (HR), SND, and RVLM neuronal activity to determine whether its effects on cardiovascular regulation are dependent on CCK1 receptors and vagal afferent transmission. To mimic gastric leptin, leptin (15–30 μg/kg) was administered close to the coeliac artery in anesthetized, artificially ventilated Sprague-Dawley rats. Within 5 min, leptin selectively decreased the activity of RVLM neurons also inhibited by CCK (−27 ± 4%; P < 0.001; n = 15); these inhibitory effects were abolished following administration of the CCK1 receptor antagonist lorglumide. Leptin significantly decreased AP and HR (−10 ± 2 mmHg, P < 0.001; and −8 ± 2 beats/min, P < 0.01; n = 35) compared with saline (−1 ± 2 mmHg, 3 ± 2 beats/min; n = 30). In separate experiments, leptin inhibited splanchnic SND compared with saline (−9 ± 2% vs. 2 ± 3%, P < 0.01; n = 8). Bilateral cervical vagotomy abolished the sympathoinhibitory, hypotensive, and bradycardic effects of leptin ( P < 0.05; n = 6). Our results suggest that gastric leptin may exert acute sympathoinhibitory and cardiovascular effects via vagal transmission and CCK1 receptor activation and may play a separate role to adipose leptin in short-term cardiovascular regulation.

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Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats

Journal of Nutrition and Metabolism ◽

10.1155/2015/157520 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Catherine Crinigan ◽

Matthew Calhoun ◽

Karen L. Sweazea

Keyword(s):

Kidney Disease ◽

Renal Mass ◽

Early Stage ◽

Young Male ◽

Protective Effects ◽

Sprague Dawley ◽

High Fat ◽

Short Term ◽

Sprague Dawley Rats ◽

The Impact

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

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Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽

10.1161/hyp.36.suppl_1.723-a ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 723-723

Author(s):

Qing-Feng Tao ◽

Diego Martinez vasquez ◽

Ricardo Rocha ◽

Gordon H Williams ◽

Gail K Adler

Keyword(s):

Myocardial Infarction ◽

Drinking Water ◽

Mineralocorticoid Receptor ◽

Critical Role ◽

Weight Ratio ◽

Myocardial Necrosis ◽

Receptor Activation ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

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Selected Contribution: Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.5.2001 ◽

2001 ◽

Vol 90 (5) ◽

pp. 2001-2006 ◽

Cited By ~ 137

Author(s):

D. D. Fuller ◽

A. G. Zabka ◽

T. L. Baker ◽

G. S. Mitchell

Keyword(s):

Receptor Antagonist ◽

Phrenic Nerve ◽

Receptor Activation ◽

Sprague Dawley ◽

Nerve Activity ◽

Sprague Dawley Rats ◽

Episodic Hypoxia ◽

Baseline Levels ◽

Long Term Facilitation

Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (∫Phr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial Po 2 = 40 ± 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [ 1) control ( n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia ( n = 7 each)]. Ketanserin transiently decreased ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.

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Aortic Stiffness and Diastolic Dysfunction in Sprague Dawley Rats Consuming Short-Term Fructose Plus High Salt Diet

Integrated Blood Pressure Control ◽

10.2147/ibpc.s257205 ◽

2020 ◽

Vol Volume 13 ◽

pp. 111-124

Author(s):

Dragana Komnenov ◽

Peter E Levanovich ◽

Natalia Perecki ◽

Charles S Chung ◽

Noreen F Rossi

Keyword(s):

Diastolic Dysfunction ◽

Aortic Stiffness ◽

High Salt ◽

Sprague Dawley ◽

Short Term ◽

High Salt Diet ◽

Salt Diet ◽

Sprague Dawley Rats

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Post-initiation inhibitory effects of green tea catechins on 7,12-dimethylbenz[a]anthracene-induced mammary gland carcinogenesis in female Sprague–Dawley rats

Cancer Letters ◽

10.1016/s0304-3835(97)04749-6 ◽

1997 ◽

Vol 116 (1) ◽

pp. 47-52 ◽

Cited By ~ 35

Author(s):

Hikaru Tanaka ◽

Masao Hirose ◽

Mayumi Kawabe ◽

Masashi Sano ◽

Yasuko Takesada ◽

...

Keyword(s):

Mammary Gland ◽

Green Tea ◽

Sprague Dawley ◽

Inhibitory Effects ◽

Tea Catechins ◽

Green Tea Catechins ◽

Sprague Dawley Rats

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Histomorphometric effects of Kigelia africana (Bignoniaceae) fruit extract on the testis following short-term treatment with cisplatin in male Sprague–Dawley rats

Middle East Fertility Society Journal ◽

10.1016/j.mefs.2010.07.001 ◽

2010 ◽

Vol 15 (3) ◽

pp. 200-208 ◽

Cited By ~ 17

Author(s):

O.O. Azu ◽

F.I.O. Duru ◽

A.A. Osinubi ◽

A.A. Oremosu ◽

C.C. Noronha ◽

...

Keyword(s):

Term Treatment ◽

Sprague Dawley ◽

Short Term ◽

Short Term Treatment ◽

Fruit Extract ◽

Sprague Dawley Rats

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Early Occurrence of Spontaneous Tumors in CD-1 Mice and Sprague—Dawley Rats

Toxicologic Pathology ◽

10.1080/01926230490440871 ◽

2004 ◽

Vol 32 (4) ◽

pp. 371-374 ◽

Cited By ~ 60

Author(s):

Woo-Chan Son ◽

Chirukandath Gopinath

Keyword(s):

Life Sciences ◽

Male Rats ◽

Sprague Dawley ◽

Control Groups ◽

Oral Gavage ◽

Short Term ◽

Young Control ◽

Sprague Dawley Rats ◽

Early Occurrence ◽

General Profile

It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague—Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK, were collected and evaluated. The route of administration was either dietary or oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50—80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50—80 weeks and at 2 years was pituitary adenoma.

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Short-term docosapentaenoic acid (22 : 5n-3) supplementation increases tissue docosapentaenoic acid, DHA and EPA concentrations in rats

British Journal Of Nutrition ◽

10.1017/s0007114509991334 ◽

2009 ◽

Vol 103 (1) ◽

pp. 32-37 ◽

Cited By ~ 63

Author(s):

Gunveen Kaur ◽

Denovan P. Begg ◽

Daniel Barr ◽

Manohar Garg ◽

David Cameron-Smith ◽

...

Keyword(s):

Skeletal Muscle ◽

Docosapentaenoic Acid ◽

Physiological Effect ◽

Sprague Dawley ◽

Short Term ◽

Term Study ◽

Chain Pufa ◽

Short Term Study ◽

Sprague Dawley Rats ◽

Tissue Site

The metabolic fate of dietary n-3 docosapentaenoic acid (DPA) in mammals is currently unknown. The aim of the present study was to determine the extent of conversion of dietary DPA to DHA and EPA in rats. Four groups of male weanling Sprague–Dawley rats (aged 5 weeks) were given 50 mg of DPA, EPA, DHA or oleic acid, daily for 7 d by gavage. At the end of the treatment period, the tissues were analysed for concentrations of long-chain PUFA. DPA supplementation led to significant increases in DPA concentration in all tissues, with largest increase being in adipose (5-fold) and smallest increase being in brain (1·1-fold). DPA supplementation significantly increased the concentration of DHA in liver and the concentration of EPA in liver, heart and skeletal muscle, presumably by the process of retroconversion. EPA supplementation significantly increased the concentration of EPA and DPA in liver, heart and skeletal muscle and the DHA concentration in liver. DHA supplementation elevated the DHA levels in all tissues and EPA levels in the liver. Adipose was the main tissue site for accumulation of DPA, EPA and DHA. These data suggest that dietary DPA can be converted to DHA in the liver, in a short-term study, and that in addition it is partly retroconverted to EPA in liver, adipose, heart and skeletal muscle. Future studies should examine the physiological effect of DPA in tissues such as liver and heart.

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