期刊
HYPERTENSION
卷 35, 期 1, 页码 329-336出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.35.1.329
关键词
risk factors; aorta; carotid arteries; vasoconstriction; diet; cholesterol; gene expression
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL054246] Funding Source: NIH RePORTER
In the C57BL/6J mice model, we investigated whether obesity affects the function or expression of components of the tissue renin-angiotensin system and whether endothelin (ET)-1 contributes to these changes. ACE activity (nmol.L His-Leu.mg protein(-1)) was measured in lung, kidney, and liver in control (receiving standard chow) and obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone or in combination with LU135252, an orally active ETA receptor antagonist. ACE mRNA expression was measured in the kidney, and the effects of LU135252 on purified human ACE were determined. Aortic and renal tissue ET-1 protein content was measured, and the vascular contractility to angiotensin II was assessed. Obesity was associated with a tissue-specific increase in ACE activity in the kidney (55 +/- 4 versus 33 +/- 3 nmol/L) but not in the lung (34 +/- 2 versus 32 +/- 2 nmol/L). Long-term LU135252 treatment completely prevented this activation (13.3 +/- 0.3 versus 55 +/- 4 nmol/L, P<0.05) independent of ACE mRNA expression, body weight, or renal ET-1 protein but did not affect pulmonary or hepatic ACE, activity. Obesity potentiated contractions in response to angiotensin II in the aorta (from 6+/-2% to 33 +/- 5% KCl) but not in the carotid artery (4 +/- 1% to 3.6 +/- 1% KCl), an effect that was completely prevented with LU135252 treatment (6 +/- 0.4% versus 33 +/- 5% KCl). No effect of LU135252 on purified ACE was observed. Thus, obesity is associated with the activation of renal ACE in vivo independent of its mRNA expression and enhanced vascular contractility to angiotensin II. These effects are regulated by ET in an organ-specific manner, providing novel mechanisms by which ET antagonists may exert organ protection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据