Tran L T, MacLeod K M, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.
Mol Cell Biochem. 2009 May;325(1-2):89-97. doi: 10.1007/s11010-008-0023-z. Epub 2009 Jan 13.
Two of the most potent vasoconstrictors, endothelin-1 (ET-1) and angiotensin II (Ang II), are upregulated in fructose hypertensive rats. It is unknown whether an interrelationship exists between these peptides that may contribute to the development of fructose-induced hypertension. The objective of this study was to investigate the existence of an interaction between the endothelin and renin angiotensin systems that may play a role in the development of fructose-induced hypertension. High fructose feeding and treatment with either bosentan, a dual endothelin receptor antagonist, or with L-158,809, an angiotensin type 1 receptor antagonist, were initiated simultaneously in male Wistar rats. Systolic blood pressure, fasted plasma parameters, insulin sensitivity, plasma Ang II, and vascular ET-1-immunoreactivity were determined following 6 weeks of high fructose feeding. Rats fed with a high fructose diet exhibited insulin resistance, hyperinsulinemia, hypertriglyceridemia, hypertension, and elevated plasma Ang II. Treatment with either bosentan or L-158,809 significantly attenuated the rise in blood pressure with no effect on insulin levels or insulin sensitivity in fructose-fed rats. Bosentan treatment significantly reduced plasma Ang II levels, while L-158,809 treatment significantly increased vascular ET-1-immunoreactivity in fructose-fed rats. Thus, treatment with the endothelin receptor antagonist prevented the development of fructose-induced hypertension and decreased plasma Ang II levels. These data suggest that ET-1 contributes to the development of fructose-induced hypertension through modulation of Ang II levels.
两种最有效的血管收缩剂，内皮素-1（ET-1）和血管紧张素II（Ang II），在果糖诱导的高血压大鼠中上调。尚不清楚这些肽之间是否存在相互关系，这可能导致果糖诱导的高血压的发展。本研究的目的是调查内皮素和肾素血管紧张素系统之间是否存在相互作用，这可能在果糖诱导的高血压的发展中起作用。在雄性Wistar大鼠中同时开始高果糖喂养并用波生坦（一种双重内皮素受体拮抗剂）或L-158,809（一种血管紧张素1型受体拮抗剂）进行治疗。在高果糖喂养6周后测定收缩压、空腹血浆参数、胰岛素敏感性、血浆Ang II和血管ET-1免疫反应性。喂食高果糖饮食的大鼠表现出胰岛素抵抗、高胰岛素血症、高甘油三酯血症、高血压和血浆Ang II升高。用波生坦或L-158,809治疗可显著减轻果糖喂养大鼠的血压升高，对胰岛素水平或胰岛素敏感性无影响。波生坦治疗可显著降低果糖喂养大鼠的血浆Ang II水平，而L-158,809治疗可显著增加果糖喂养大鼠的血管ET-1免疫反应性。因此，用内皮素受体拮抗剂治疗可预防果糖诱导的高血压的发展并降低血浆Ang II水平。这些数据表明，ET-1通过调节Ang II水平促进果糖诱导的高血压的发展。
