Alvarez de Sotomayor Maria, Bueno Rosario, Pérez-Guerrero Concepción, Herrera Maria Dolores
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.
J Vasc Res. 2007;44(5):354-64. doi: 10.1159/000102303. Epub 2007 May 4.
The effect of treatment with either 200 mg x kg(-1) of L-carnitine (LC) or propionyl-L-carnitine (PLC) was studied on endothelial dysfunction of small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats.
Systolic blood pressure (SBP) was measured and endothelial and vascular functions were assessed by the effect of carbachol (CCh) and phenylephrine (Phe). O2- produced by SMA and eNOS expression were evaluated by chemiluminescence and Western blot, respectively.
Although SBP was not affected, endothelial relaxation increased in both LC- and PLC-treated SHR. Nevertheless, the CCh-induced contraction remained sensitive to indomethacin in these rats. On the contrary, NO participation was increased in all the groups except for LC-treated WKY. Furthermore, high concentrations of Phe produced NO-dependent relaxation of SMA from PLC-treated rats. Both compounds decreased basal and NADPH-stimulated O2- in SHR toward values observed in WKY. Only PLC increased eNOS protein expression in SHR. Neither LC nor PLC affected endothelium-derived hyperpolarizing factor-induced relaxation.
LC and its propionate improved endothelial responses of SMA from SHR by decreasing O2- production and thus increasing NO availability. PLC also increased NO synthesis by enhancing eNOS expression.
研究了用200 mg·kg⁻¹的左旋肉碱(LC)或丙酰左旋肉碱(PLC)处理对自发性高血压大鼠(SHR)和正常血压的Wistar-Kyoto(WKY)大鼠肠系膜小动脉(SMA)内皮功能障碍的影响。
测量收缩压(SBP),并通过卡巴胆碱(CCh)和去氧肾上腺素(Phe)的作用评估内皮和血管功能。分别通过化学发光和蛋白质印迹法评估SMA产生的O₂⁻和eNOS表达。
尽管SBP未受影响,但LC和PLC处理的SHR的内皮舒张均增加。然而,在这些大鼠中,CCh诱导的收缩对吲哚美辛仍敏感。相反,除LC处理的WKY外,所有组中NO的参与均增加。此外,高浓度的Phe使PLC处理的大鼠的SMA产生NO依赖性舒张。两种化合物均使SHR中的基础和NADPH刺激的O₂⁻降低至WKY中观察到的值。只有PLC增加了SHR中eNOS蛋白的表达。LC和PLC均未影响内皮衍生的超极化因子诱导的舒张。
LC及其丙酸盐通过减少O₂⁻产生从而增加NO的可用性,改善了SHR的SMA的内皮反应。PLC还通过增强eNOS表达增加了NO的合成。