Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension.

Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension.
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DOI:
10.3389/fphar.2012.00103
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发表时间:
2012
影响因子:
5.6
通讯作者:
Fernández-Alfonso MS
Fernández-Alfonso MS
中科院分区:
医学2区
文献类型:
--
作者:
Gálvez-Prieto B;Somoza B;Gil-Ortega M;García-Prieto CF;de Las Heras AI;González MC;Arribas S;Aranguez I;Bolbrinker J;Kreutz R;Ruiz-Gayo M;Fernández-Alfonso MS

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瘦素通过内皮依赖性和非依赖性机制引起血管舒张。瘦素由血管周围脂肪组织(PVAT)合成。本研究的假设是自发性高血压大鼠(SHR) PVAT中瘦素产生的减少可能导致该激素的旁分泌抗收缩作用减弱。我们通过Wistar-Kyoto (WKY)和SHR测定了主动脉(i) PVAT中瘦素mRNA和蛋白水平,(ii)瘦素和PVAT对收缩反应的影响,以及(iii)瘦素诱导的松弛和一氧化氮(NO)产生。SHR引起的PVAT中瘦素mRNA和蛋白的表达显著降低。只有在WKY中,PVAT和外源性瘦素(10−9 M)的存在使血管紧张素II的浓度-反应曲线明显变钝。这种抗收缩作用是内皮依赖的。瘦素诱导的血管舒张在SHR中比在WKY中更小,并且也是内皮依赖性的。此外,与SHR相比,WKY中响应急性瘦素的内皮NO的释放更高,但在没有内皮的情况下完全被消除。综上所述,PVAT在SHR中的抗收缩作用减弱可能是由于PVAT衍生的瘦素减少,而瘦素对内皮NO合成酶的激活受损可能导致内皮NO释放的作用减弱。
Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10−9 M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.
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