Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Circulation. 2011 Sep 6;124(10):1160-71. doi: 10.1161/CIRCULATIONAHA.111.027375. Epub 2011 Aug 15.
Perivascular adipose tissue (PVAT)-derived relaxing factor (PVATRF) significantly regulates vascular tone. Its chemical nature remains unknown. We determined whether palmitic acid methyl ester (PAME) was the PVATRF and whether its release and/or vasorelaxing activity decreased in hypertension.
Using superfusion bioassay cascade technique, tissue bath myography, and gas chromatography/mass spectrometry, we determined PVATRF and PAME release from aortic PVAT preparations of Wistar Kyoto rats and spontaneously hypertensive rats. The PVAT of Wistar Kyoto rats spontaneously and calcium dependently released PVATRF and PAME. Both induced aortic vasorelaxations, which were inhibited by 4-aminopyridine (2 mmol/L) and tetraethylammonium 5 and 10 mmol/L but were not affected by tetraethylammonium 1 or 3 mmol/L, glibenclamide (3 μmol/L), or iberiotoxin (100 nmol/L). Aortic vasorelaxations induced by PVATRF- and PAME-containing Krebs solutions were not affected after heating at 70°C but were equally attenuated after hexane extractions. Culture mediums of differentiated adipocytes, but not those of fibroblasts, contained significant PAME and caused aortic vasorelaxation. The PVAT of spontaneously hypertensive rats released significantly less PVATRF and PAME with an increased release of angiotensin II. In addition, PAME-induced relaxation of spontaneously hypertensive rats aortic smooth muscle diminished drastically, which was ameliorated significantly by losartan.
We found that PAME is the PVATRF, causing vasorelaxation by opening voltage-dependent K+ channels on smooth muscle cells. Diminished PAME release and its vasorelaxing activity and increased release of angiotensin II in the PVAT suggest a noble role of PVAT in pathogenesis of hypertension. The antihypertensive effect of losartan is attributed partly to its reversing diminished PAME-induced vasorelaxation.
血管周围脂肪组织（PVAT）衍生的舒张因子（PVATRF）可显著调节血管张力。其化学性质尚不清楚。我们确定棕榈酸甲酯（PAME）是否为 PVATRF，以及其在高血压中的释放和/或舒张活性是否降低。
我们使用超扩散生物测定级联技术、组织浴肌动描记术和气相色谱/质谱法，从 Wistar Kyoto 大鼠和自发性高血压大鼠的主动脉 PVAT 制剂中测定 PVATRF 和 PAME 的释放。Wistar Kyoto 大鼠的 PVAT 自发且钙离子依赖性地释放 PVATRF 和 PAME。两者均诱导主动脉舒张，4-氨基吡啶（2 mmol/L）和四乙铵 5 和 10 mmol/L 可抑制该舒张，但四乙铵 1 或 3 mmol/L、格列本脲（3 μmol/L）或 Iberiotoxin（100 nmol/L）对其无影响。PVATRF 和 PAME 含 Krebs 溶液诱导的主动脉舒张在 70°C 加热后不受影响，但在正己烷提取后同样减弱。分化脂肪细胞的培养基，而不是成纤维细胞的培养基，含有大量的 PAME 并引起主动脉舒张。自发性高血压大鼠的 PVAT 释放的 PVATRF 和 PAME 明显减少，同时血管紧张素 II 的释放增加。此外，PAME 诱导的自发性高血压大鼠主动脉平滑肌舒张明显减弱，洛沙坦可显著改善。
我们发现 PAME 是 PVATRF，通过打开平滑肌细胞上的电压依赖性 K+通道引起血管舒张。PVAT 中 PAME 释放减少及其舒张活性降低以及血管紧张素 II 释放增加提示 PVAT 在高血压发病机制中具有重要作用。洛沙坦的降压作用部分归因于其逆转 PAME 诱导的舒张减弱。
