背景及目的：目前已知胰島素(insulin)與類胰島素生長因子-1(insulin-like growth factor-1; IGF-1)可經由內皮細胞產生一氧化氮(nitric oxide; NO)而達到調節血管張力的功能。先前的研究發現在高血壓的模式下，內皮依賴的血管舒張反應有受損的現象。且許多研究顯示，運動可藉由增進一氧化氮生物可用性(NO bioavailability)而改善血管功能。然而，尚無研究探討高強度運動對於高血壓由胰島素及類胰島素生長因子-1所媒介之血管舒張反應的影響。故本研究之目的在於探討高血壓之動物模式模式下，高強度運動對於由胰島素及類胰島素生長因子-1所媒介之血管舒張反
應的影響，及其潛在機制。
方法：本研究將實驗動物分為三組，高血壓鼠(spontaneously hypertensive rat; SHR)隨機分成運動組和非運動組，再以週齡相符的正常血壓鼠(Wistar Kyoto rat; WKY)作為對照組。運動組以跑
步機作單次高強度運動介入，速度為28-30公尺/分鐘，跑至筋疲力竭為止。在運動後立即犧牲，取出老鼠的胸主動脈作為血管舒張反應之分析用。我們加入特定的抑制劑，檢視phosphatidylinositol-3 kinase (PI3-K)及一氧化氮合成酶(nitric oxide synthase; NOS)在此血管反應中扮演的角色；也測試由一氧化氮提供者(sodium nitroprusside ;SNP)所誘發的血管反應；最後，我們用超氧化歧化酶(superoxide dismutase; SOD)檢視氧化性壓力對此血管反應的影響。
結果：我們發現(1)相較於正常血壓鼠，高血壓鼠由胰島素和類胰島素生長因子-1所媒介之血管舒張反應明顯地受損；(2)高強度運動介入可明顯地改善高血壓鼠由胰島素和類胰島素生長因子-1所媒介之血管舒張反應；(3)這些血管舒張反應的改變與PI3-K及一氧化氮
合成酶的活性變化有關；(4)SNP所媒介之非內皮依賴的血管舒張反應於三組間無顯著變化；(5)運動引起血管功能改善之效果可能與過氧化物的降低有關。
結論：高強度運動介入可經由增加PI3-K及一氧化氮合成酶的活性明顯地改善由高血壓所引起之血管功能受損情形，其潛在機制和過
氧化物的下降有關。本研究提供運動如何改善高血壓血管失能之部份理論基礎。

Background and Purpose: Insulin and insulin-like growth factor-1 (IGF-1) play important roles in the regulation of vascular tone via producing endothelium-derived nitric oxide (EDNO). Previous studies have demonstrated the impairments of endothelium-dependent vasorelaxation in hypertension. Furthermore, exercise is well known to improve vascular function through enhancing NO bioavailability. However, the effects of high-intensity exercise on insulin- and IGF-1-mediated vasorelaxation in
hypertension remain unknown. Therefore, the aim of this study was to investigate the effects of high-intensity exercise on vasorelaxant responses to insulin and IGF-1 in spontaneously hypertensive rats (SHR) and the underlying mechanisms.
Methods: Three groups of rats were used in this study: SHR with high-intensity exercise (SHR+Ex), sedentary SHR (SHR),
and Wistar-Kyoto rat (WKY) groups. The SHR+Ex group ran on treadmill at the speed of 28-30 m/min until exhaustion. The WKY group was used as normotensive control group. After high-intensity exercise, the thoracic aortas of rats were isolated immediately to measure insulin- and IGF-1-mediated vascular responses. Selective inhibitors were used to examine the roles of nitric oxide synthase (NOS) and phosphatidylinositol-3 kinase (PI3-K) in the vasorelaxation. The vascular response induced by sodium nitroprusside (SNP, a NO donor) was also examined. Finally, superoxide dismutase (SOD), a superoxide scavenger, was used to evaluate the role of superoxide production in the vasorelaxation.
Results: We found that, 1) insulin- and IGF-1-mediated
vasorelaxation was significantly reduced in SHR compared with that in WKY; 2) high-intensity exercise ameliorated these adverse effects in SHR+Ex group; 3) the alterations of vascular responses to insulin and IGF-1 were mainly due
to the varied activities of PI3-K and NOS; 4) SNP-induced,
endothelium-independent vasorelaxation was comparable among three groups; 5) the exercise-induced beneficial effects on vascular dysfunction in hypertension could be related to the reduced level of superoxide production.
Conclusions: Our findings suggested that high-intensity exercise ameliorated the hypertension-induced vascular dysfunction through the endothelium-dependent PI3-K-NOS pathway, which was associated with the reduced level of superoxide production. This study supports the effectiveness of exercise intervention in reversing vascular dysfunction in hypertension.

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