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Direct effect of leptin on endothelial function and their changes in patients with essential hypertension

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Author:
No author available
Journal Title:
JOURNAL OF THE FOURTH MILITARY MEDICAL UNIVERSITY
Issue:
24
DOI:
10.3321/j.issn:1000-2790.2009.24.065
Key Word:
瘦素;原发性高血压;一氧化氮;内皮;leptin;essential hypertension;nitric oxide;endothelium

Abstract: AIM:To observe serum leptin changes in patients with essential hypertension and direct effect of leptin on endothelial function and its possible signaling pathways.METHODS:Sixtyfour patients with essential hypertension(EH)and 60 normotensive subjects matched for age and sex were involved to observe the change of serum leptin,endothelin-1(ET-1)and nitric oxide (NO).Cell culture technique was used to observe the direct effect of leptin on NO and ET-1 prodution from human umbilical vein endothelial cells(HUVEC).Tyrosine kinase inhibitor(genestein)and phosphatidylinositol 3-kinase(PI 3-kinase)inhibitor (wortmannin)were added to confer the possible signaling pathway of above effect.RESULTS:EH patients had high serum leptin [(7.95±4.01)μg/L vs(5.68±4.56)μg/L,P<0.05],ET-1[(104.24±34.18)ns/L vs(58.26±11.0)ng/L,P<0.001]and ET-1/NO[(2.12±1.46)vs(1.24±1.21),P<0.05];Serum leptin level was significantly positively correlated with setum ET-1(r=0.427,P<0.05)and systolic blood pressure(r=0.312,P<0.05);High concentration of leptin(1,10 mg/L)had direct effects of promoting the NO secretion from HUVECs;no matter high or low concentration of leptin have no inSuence on ET-1 synthesis from HUVECs;The effect of leptin on NO was blocked by either tyrosine kinase inhibitor-genestein or PI 3-kiBase inhibitor-wortmannin.CONCLUSION:EH patients had leptin resistance and endothelial dysfunction;Both tyrosine kinase and PI 3-kinase were the possible post-receptor signal transduction effector molecules of leptin in HUVECs on NO production;Abnormal receptor or post-receptor signaling transduction of leptin may be the pathological causes of both leptin resistance and endothelial dysfunction in EH.

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