L-carnitine and propionyl-L-camitine improve endothelial dysfunction in spontaneously hypertensive rats: Different participation of NO and COX-products
L-carnitine and propionyl-L-camitine improve endothelial dysfunction in spontaneously hypertensive rats: Different participation of NO and COX-products
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DOI：
10.1016/j.lfs.2005.01.035
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发表时间：
2005-09-09
期刊：
影响因子：
6.1
通讯作者：
Herrera, MD
中科院分区：
文献类型：
--
作者：
Bueno, R;de Sotomayor, MA;Herrera, MD
左旋肉碱和丙酰左旋肉碱是心血管病理治疗的补充剂。在自发性高血压大鼠 (SHR) 和正常血压 Wistar 京都大鼠 (WXY) 中使用 200 mg/kg 左旋肉碱或丙酰左旋肉碱治疗 8 周后，研究了它们对高血压内皮功能障碍的影响。通过卡巴胆碱诱导的舒张（CCh 10(-8) 至 10(-4) M）评估主动脉环的内皮功能，并在抑制剂存在下对相关因素进行表征：L-NAME、吲哚美辛、TXA(2)/PGH(2) Tp 受体拮抗剂 ICI-192,605 和血栓素合成酶抑制剂-Tp 受体拮抗剂 Ro-68,070。还观察到对去氧肾上腺素诱导的收缩的影响。为了鉴定血管活性 COX 衍生产物的性质，对孵育介质的酶免疫测定进行了评估。通过与超氧化物歧化酶和过氧化氢酶一起孵育来评估活性氧的参与。通过血清NO2+NO3浓度评价一氧化氮的产生。这两种化合物的治疗均改善了 SHR 环的内皮功能，且血压没有变化。丙酰-L-肉碱增加 WKY 和 SHR 中 NO 的参与。由于 TXA(2) 产量增加，L-肉碱减少了 WKY 中对 CCh 的内皮依赖性反应。在 SHR 和 WKY 中，左旋肉碱提高了 PGI(2) 的浓度并增加了 NO 的参与。 SOD 加过氧化氢酶存在下的结果表明，它可能与左旋肉碱和丙酰左旋肉碱的抗氧化特性有关。两种化合物效果的比较表明，两者都可以减少活性氧并增加 SHR 中内皮依赖性舒张中 NO 的参与。然而，只有左旋肉碱能够增加血管舒张剂 PGI(2) 的释放，甚至增强血压正常大鼠中 TXA(2) 的产生。 (c) 2005 Elsevier Inc. 保留所有权利。
L-carnitine and propionyl-L-carnitine are supplements to therapy in cardiovascular pathologies. Their effect on endothelial dysfunction in hypertension was studied after treatment with either 200 mg/kg of L-carnitine or propionyl-L-carnitine during 8 weeks of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WXY). Endothelial function was assessed in aortic rings by carbachol-induced relaxation (CCh 10(-8) to 10(-4) M) and factors involved were characterized in the presence of the inhibitors: L-NAME, indomethacin, the TXA(2)/ PGH(2) Tp receptor antagonist ICI-192,605 and the thromboxane synthetase inhibitor-Tp receptor antagonist, Ro-68,070. The effect on phenylephrine-induced contractions was also observed. To identify the nature of vasoactive COX-derived products, enzyme-immunoassay of incubation media was assessed. Involvement of reactive oxygen species was evaluated by incubating with superoxide dismutase and catalase. Nitric oxide production was evaluated by serum concentration of NO2+NO3. Treatment with both compounds improved endothelial function of rings from SHR without blood pressure change. Propionyl-L-carnitine increased NO participation in WKY and SHR. L-carnitine reduced endothelium-dependent responses to CCh in WKY due to an increase of TXA(2) production. In both SHR and WKY, L-carnitine enhanced concentration of PGI(2) and increased participation of NO. Results in the presence of SOD plus catalase show that it might be related to antioxidant properties of L-carnitine and propionyl-L-carnitine. Comparison between the effect of both compounds shows that both may reduce reactive oxygen species and increase NO participation in endothelium-dependent relaxations in SHR. However, only L-carnitine was able to increase the release of the vasodilator PGI(2) and even enhanced TXA(2) production in normotensive rats. (c) 2005 Elsevier Inc. All rights reserved.