Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC) and Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Br J Pharmacol. 2012 Feb;165(3):633-42. doi: 10.1111/j.1476-5381.2011.01430.x.
Visceral fat has been linked to metabolic disturbances and increased risk for cardiovascular disease and type 2 diabetes. Recent studies propose a paracrine role for periadventitial adipose tissue in the control of arterial vascular tone. This regulation depends on the anatomical integrity of the vessels and involves a transferable mediator(s) (adipokine) released from either periadventitial adipocytes or perivascular adipose tissue. Although a number of adipokines with vasoactive properties have been identified, a still unidentified adipocyte-derived relaxing factor (ADRF) plays a major role in the periadventitial vasoregulation of visceral arteries, such as the aorta and mesenteric arteries. ADRF is released by visceral periadventitial adipocytes and primarily produces endothelium-independent vasorelaxation by opening voltage-dependent (K(v) ) K(+) channels in the plasma membrane of smooth muscle cells. At least in part, KCNQ (K(v) 7) channels could represent the subtype of K(v) channels involved. Glibenclamide-sensitive K(ATP) channels are not involved or play a minor role. The 'third gas', namely H(2) S, could represent ADRF. Alterations in the paracrine control of arterial tone by visceral periadventitial adipose tissue have been found in animal models of hypertension and metabolic disease. ADRF, or perhaps its putative targets, might represent exciting new targets for the development of drugs for treatment of cardiovascular and metabolic disorders.
This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.
内脏脂肪与代谢紊乱以及心血管疾病和 2 型糖尿病风险增加有关。最近的研究提出,血管外膜脂肪组织在控制动脉血管张力方面具有旁分泌作用。这种调节依赖于血管的解剖完整性,涉及从血管外膜脂肪细胞或血管周围脂肪组织释放的可转移介质(脂肪因子)。虽然已经确定了许多具有血管活性的脂肪因子,但一种尚未确定的脂肪细胞衍生的舒张因子(ADRF)在内脏动脉的血管外膜调节中起着重要作用,如主动脉和肠系膜动脉。ADRF 由内脏血管外膜脂肪细胞释放,主要通过打开平滑肌细胞膜上的电压依赖性(K(v))K(+)通道来产生内皮依赖性血管舒张。至少部分 KCNQ(K(v)7)通道可能代表涉及的 K(v)通道亚型。Glibenclamide 敏感的 K(ATP)通道不参与或作用较小。“第三种气体”,即 H(2)S,可能代表 ADRF。在高血压和代谢疾病的动物模型中发现,内脏血管外膜脂肪组织对动脉张力的旁分泌控制发生了改变。ADRF 或其假定的靶标,可能代表治疗心血管和代谢紊乱药物开发的令人兴奋的新靶标。
本文是关于脂肪和血管反应性的专题部分的一部分。要查看该部分中的其他文章,请访问 http://dx.doi.org/10.1111/bph.2012.165.issue-3。