Cardiorespiratory responses to intracerebroventricular injection of neuropeptide Y in anaesthetised dogs

Morton, K.D. Richardson; McCloskey, M.J.D.; Potter, Erica K.

doi:10.1016/s0167-0115(99)00021-x

Cited by 19 publications

(8 citation statements)

References 37 publications

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“…These findings suggest that some but not all of the leptin-induced sympathetic activation are mediated via hypothalamic melanocortin system. Because central administration of neuropeptide Y (NPY) reduces BP in rats and dogs (47,48), decreased hypothalamic NPY production by exogenous administration of leptin (49) and in transgenic skinny mice (Y. Ogawa et al, unpublished data) might be involved in hypertensive effect of leptin.…”

Section: Discussionmentioning

confidence: 99%

Pathophysiological role of leptin in obesity-related hypertension

Aizawa-Abe¹,

Ogawa²,

Masuzaki³

et al. 2000

J. Clin. Invest.

437

312

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IntroductionObesity is defined as increased mass of adipose tissue and confers a higher risk of arterial blood pressure (BP) elevation or hypertension (1-4). On the other hand, weight reduction lowers BP in obese hypertensive subjects (5-8), suggesting an important association between energy homeostasis and BP. However, the mechanism for that association is poorly understood. Obesity-related hypertension may be secondary to insulin resistance and/or hyperinsulinemia (2,3,8). Several lines of evidence have also suggested that increased sympathetic nerve activity may contribute to the development of obesity-related hypertension (2, 6, 7).The adipose tissue participates in the regulation of a variety of homeostatic processes as an endocrine organ that secretes many biologically active molecules such as FFA, adipsin, angiotensinogen,. Leptin is such an adipocyte-derived hormone that is involved in the regulation of food intake and body weight (10). It also increases the overall sympathetic nerve activity, which leads to a significant increase in energy expenditure (11-15). The biologic actions of leptin are thought to be mediated through the activation of leptin receptor that is expressed in the hypothalamus (16)(17)(18)(19). We and others demonstrated that the hypothalamic arcuate nucleus is a primary site of the satiety effect of leptin (20,21) and that its satiety effect is mediated at least partly by hypothalamic melanocortin system (22,23).Numerous studies have demonstrated that plasma leptin concentrations are elevated significantly in several models of rodent obesity and in human obesity in proportion to the degree of adiposity (24-26), suggesting the state of "leptin resistance" in obesity. Nevertheless, because of the potent pleiotropic actions of leptin, it is conceivable, though paradoxically, that hyperleptinemia may be involved in the pathogenesis of obesity and its related disorders. In this regard, a recent study reported a significant correlation between BP and plasma leptin concentrations in patients with essential hypertension (27), suggesting that leptin may play roles in the pathogenesis of obesity-related hypertension.We have recently produced transgenic skinny mice overexpressing leptin under the control of the liver-specific promoter and demonstrated that chronic hyperleptinemia results in complete disappearance of adipose tissue for a long period (28). These mice also exhibit increased glucose metabolism and insulin sensitivity, accompanied by an activation of insulin signaling in the skeletal muscle and liver (28,29). Accordingly, transgenic skinny mice will serve as the unique experimental model system with which to assess the long-term effects of leptin in vivo. To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes of transgenic skinny mice whose elevated plasma leptin concentrations are comparable to those seen in obese subjects. We also studied genetically obese KKA y mice with hyperleptinemia, in which hypothalamic melano...

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Section: Discussionmentioning

confidence: 99%

Pathophysiological role of leptin in obesity-related hypertension

Aizawa-Abe¹,

Ogawa²,

Masuzaki³

et al. 2000

J. Clin. Invest.

437

312

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“…221 In dogs, neuropeptide Y-1 receptors mediated a decrease in ventilation and BP, while neuropeptide Y-2 receptors mediated the opposite effect. 222 After central administration, neuropeptide Y decreased respiratory rate. 190 The role of neuropeptide Y in human control of breathing is not established, but some data suggest that neuropeptide Y might play a role.…”

Section: Neuropeptide Ymentioning

confidence: 99%

Hormones and Breathing

Saaresranta

Polo

2002

Chest

167

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“…Moreover, central NPY Y 2 receptor stimulation via NPY [24][25][26][27][28][29][30][31][32][33][34][35][36] significantly increased blood pressure in anesthetized dogs (20) and mean arterial pressure tended to be lower in Y 2 receptor knockout mice (21).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of NPY Y₂ receptors by PYY_3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

Nordheim

Hofbauer

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Nordheim, Ulrich, and Karl G. Hofbauer. Stimulation of NPY Y 2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens. Am J Physiol Regul Integr Comp Physiol 286: R138-R142, 2004. First published October 9, 2003 10.1152/ajpregu.00374.2003In the present experiments the gut hormone peptide YY , which inhibits neuropeptide Y (NPY) release, was used as a tool to study the cardiovascular effects of endogenous NPY under different dietary regimens in rats instrumented with a telemetry transmitter. In a first experiment, rats were placed on a standard chow diet ad libitum and in a second experiment on a high-fat diet ad libitum. After 6 wk, PYY3-36 (300 g/kg) or vehicle was injected intraperitoneally. In a third experiment, PYY3-36 or vehicle was administered after 14 days of 50% restriction of a standard chow diet. In food-restricted rats, PYY3-36 increased mean arterial pressure (7 Ϯ 1 mmHg, mean Ϯ SE, P Ͻ 0.001 vs. saline, 1-way repeated-measures ANOVA with Bonferroni t-test) and heart rate (22 Ϯ 4 beats/min, P Ͻ 0.001) during 3 h after administration. Conversely, PYY3-36 did not influence mean arterial pressure (0 Ϯ 1 mmHg) and heart rate (Ϫ8 Ϯ 5 beats/min) significantly in rats on a high-fat diet. Rats fed standard chow diet ad libitum showed an intermediate response (mean arterial pressure 4 Ϯ 1 mmHg, P Ͻ 0.05, and heart rate 5 Ϯ 2 beats/min, not significant). Thus, in our studies, divergent cardiovascular responses to PYY3-36 were observed in rats on different dietary regimens. These findings suggest that the cardiovascular effects of PYY3-36 depend on the hypothalamic NPY release, which is increased after chronic food restriction and decreased during a high-fat diet. blood pressure; heart rate; sympathetic nerve activity; neuropeptide Y; peptide YY NEUROPEPTIDE Y (NPY) is one of the strongest endogenous stimulators of food intake (13) and is abundantly expressed in hypothalamic feeding centers such as the arcuate (ARC) and paraventricular nucleus (PVN; 6, 7). It has been demonstrated that the hypothalamic content of NPY varies with nutritional state probably due to different NPY release (25,28). In addition to its role in appetite control, NPY also decreases blood pressure, heart rate (HR), and plasma norepinephrine levels after injection into the PVN (10,26,27) or the nucleus of the solitary tract (NTS) (8). Consequently, NPY-containing neurons that project from hypothalamic feeding centers (e.g., ARC, PVN) to cardiovascular centers of the brain stem (e.g., NTS) might be involved in both the regulation of energy balance and the regulation of cardiovascular function.NPY and peptide YY (PYY) are closely related polypeptides, which are composed of 36 amino acids and share considerable homology (in rats: 67%) (19). While NPY acts as a neurotransmitter, the two endogenous forms of PYY (PYY and PYY 3-36 ) are gut-derived hormones secreted by intestinal endocrine cells (L cells) into the circulation after a meal (1, 22). PYY 1-36 binds and activates at ...

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Cardiorespiratory responses to intracerebroventricular injection of neuropeptide Y in anaesthetised dogs

Cited by 19 publications

References 37 publications

Pathophysiological role of leptin in obesity-related hypertension

Pathophysiological role of leptin in obesity-related hypertension

Hormones and Breathing

Stimulation of NPY Y₂ receptors by PYY_3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

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Cardiorespiratory responses to intracerebroventricular injection of neuropeptide Y in anaesthetised dogs

Cited by 19 publications

References 37 publications

Pathophysiological role of leptin in obesity-related hypertension

Pathophysiological role of leptin in obesity-related hypertension

Hormones and Breathing

Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

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Stimulation of NPY Y₂ receptors by PYY_3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens