Effects of resistin on blood pressure regulation in rats

• Main Authors: Tung-Yueh Chuang, 莊東岳
• Other Authors: Chi-Chang Juan
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/36967204468178652677

碩士 === 國立陽明大學 === 生理學研究所 === 94 === Adipocytes secrete many bioactive proteins named adipocytokines. Previous studies suggested that adipocytokines may play an important role between insulin resistance and endothelial dysfunction. In states of hyperinsulinemia and insulin resistance, an imbalance between insulin action on endothelin-1 (ET-1) and nitric oxygen (NO) predisposes to increase vascular tone and endothelial dysfunction. Resistin, a recently described adipocytokine, has been proposed as a link between obesity and insulin resistance. In vitro study showed that resistin promoted endothelial cell activation and impaired insulin stimulated endothelial nitric oxide synthase (eNOS) activation. In isolated porcine coronary artery ring study showed that resistin reduced endothelium-dependent and endothelium-independent vasorelaxation. However, the biological function on cardiovascular system of resistin in blood pressure in vivo is not clear. We hypothesized that resistin may cause imbalance between ET-1 and NO in vivo. Male Sprague-Dawley rats (BW: 300g~350g) were used in this study. The anesthetized rats (0.5g/kg BW urethane and 0.1g/kg BW chloralose, i.p.) will be cannulated with PE-50 tubes in right jugular vein, left femoral vein, right femoral vein, and left femoral artery. The changes of blood pressure were measured via the femoral artery catheter by using a pressure transducer coupled with a polygraph recorder. Then rats will be infused with resistin or saline via the right femoral vein catheter for a total period of 180 min. One hour after resistin or saline infusion, rats will be challenged with acetylcholine (ACh), sodium nitroprusside (SNP), or ET-1. The pressure responses to these vasodilators will be recorded. To further test whether 3h-resistin-infusion causes insulin resistance in vivo, the influences of resistin on the insulin-stimulated phosphorylation of IRß and Akt in skeletal muscle, adipose tissue and thoracic aorta will be also measured. Results showed that the maximal vasomotor response to SNP and ET-1 in two groups were not different. However, we found that resistin accelerated cardiovascular recovery response to SNP and delayed cardiovascular recovery response to ET-1. In addition, the levels of IRß and Akt phosphorylation were significantly decreased in skeletal muscle, adipose tissue and aorta from resistin infusion rats compared to that from controls. After 1h-infusion, plasma glucose and insulin were significantly increased and insulin resistance was significantly increased in resistin infused rats compared to controls. Plasma resistin level also was significantly increased after 1h-infusion and 3h-infusion in resistin infused rats compared to controls.In conclusion, acute resistin infusion caused an imbalance on ET-1 and NO through interfering cardiovascular recovery. Acute resistin infusion impaired insulin signaling pathway in skeletal muscle, adipose tissue and aorta. These findings would help to elucidate the physiological role of resistin in insulin resistant-associated cardiovascular diseases.