Juan C C, Fang V S, Hsu Y P, Huang Y J, Hsia D B, Yu P C, Kwok C F, Ho L T
Department of Physiology, National Yang-Ming University, Veterans General Hospital-Taipei, Taiwan, Republic of China.
J Hypertens. 1998 Dec;16(12 Pt 1):1775-82. doi: 10.1097/00004872-199816120-00010.
To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension.
Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors.
Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension.
Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet
研究果糖诱导的高血压大鼠模型中高胰岛素血症与高血压之间的时间关系，并探讨内皮素-1（ET-1）在果糖诱导的高血压中的作用。
由于ET-1可诱导清醒大鼠产生胰岛素抵抗，我们检验了以下假设：果糖诱导的高血压大鼠模型中出现的高胰岛素血症和高血压可能是ET-1及ET(A)受体组织含量升高的后果。
给雄性Sprague-Dawley大鼠喂食富含果糖的饮食，在3周内诱导其出现收缩期高血压。持续监测血压和血浆胰岛素浓度后，在实验结束时处死动物，以测定血浆ET-1水平、主动脉环对ET-1的收缩反应以及ET-1和ET(A)受体基因表达。在另一项实验中，给予BQ-610以降低ET-1对果糖诱导的高血压大鼠的作用。
与喂食正常食物的对照大鼠相比，喂食果糖的大鼠在饮食3周后出现收缩期高血压（127±3.7对110±5.5 mmHg，P<0.01），且在出现高血压之前（107.1±32.5对48.5±14.3 pmol/l，P<0.005）和之后（96.6±63.7对50.4±5.6 pmol/l，P<0.05）均出现高胰岛素血症。虽然大鼠组之间血浆ET-1水平无差异，但表明血管对ET-1反应性收缩的主动脉环收缩-浓度曲线在这些大鼠中显著高于对照组（F1,72 = 12.34，P<0.00077）。从尾动脉提取并用ET-1和ET(A)探针进行印迹分析的信使核糖核酸显示，喂食果糖的大鼠比对照大鼠具有更高的ET-1和ET(A)受体基因表达。给喂食果糖饮食的大鼠同时给予BQ-610可显著降低高血压。结论这些发现表明，ET-1和ET(A)受体基因的血管表达升高可能介导了喂食富含果糖饮食大鼠的高血压和高胰岛素血症的发生。
