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Title: Some vascular effects of hormones contributing to the regulation of appetite

Abstract:

Adipose tissue secrets a large variety of highly active proteins like leptin and resistin, regulating metabolism, appetite, as well as modulating inflammatory process. These adipose – derived proteins are thought to contribute to the pathogenesis of endothelial dysfunction, atherosclerosis, hypertension, and insuline resistance. Oxidative stress and overproduction of reactive oxygen species (ROS) is a key factor in the pathogenesis of endothelial dysfunction. NADPH oxidase are the main source of superoxide in the veins and arteries of individuals with atherosclerosis risk factors. Because oxidative stress and increased superoxide production by NADPH oxidase are critical in pathogenesis of endothelial dysfunction, we aimed to study the effects of leptin and resistin on vascular superoxide production, NADPH oxidase activity and endothelial function. We also studied the vascular effects of ghrelin, a novel peptide hormone which biological effects appear to be opposite to those of leptin. Ghrelin was shown to decrease blood pressure and improve endothelial function. Superoxide production and NADPH oxidase activity were determined by lucigenin-enhanced chemiluminescence (5 μM) from intact human vessel rings (internal mammary arteries – IMA and saphenous veins - SV) from patients undergoing coronary artery bypass graft surgery and from animals thoracic aorta (rats - WKY, SHR: mice - C57BL/6, apoE knock-out, p47phox knock-out). Vascular effects of leptin, resistin and ghrelin on vascular wall tension, as well as, on nitric oxide dependent endothelial function were analysed using isometric tension studies in vitro (organ bath technique). Our data demonstrate that leptin and resistin induce significant endothelial dysfunction in mice by direct NADPH oxidase activation and increased superoxide production. Additionally, leptin has been shown to activate endothelial nitric oxide synthase in thoracic aorta in mice. In the present study we show, that ghrelin is able to inhibit directly vascular superoxide production and NADPH oxidase activity in SHR as well as abolish the difference between SHR and WKY. The antioxidant activities of ghrelin were also proved in human vessels in which greater vasorelaxation dependent on NO and induced by acetylcholine was observed. Inhibition of vascular NADPH oxidase and superoxide production by ghrelin may indicate its potential antiatherosclerotic properties, however, this suggestion requires further investigation.

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia

Degree grantor:

Wydział Lekarski

Promoter:

Ryszard Korbut

Date issued:

2008

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:887

Call number:

ZB-109877

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Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

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Last modified:

Sep 10, 2019

In our library since:

Nov 21, 2012

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7

Number of object content views in PDF format

7

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/887

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ZB-109877 Sep 10, 2019
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