Moderate-Intensity Exercise Improves Mesenteric Arterial Function in Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats: A Shift in the Relative Importance of Endothelium-Derived Relaxing Factors (EDRF).

Moderate-Intensity Exercise Improves Mesenteric Arterial Function in Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats: A Shift in the Relative Importance of Endothelium-Derived Relaxing Factors (EDRF).
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DOI:
10.3390/biomedicines11041129
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发表时间:
2023-04-08
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
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--
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运动对心血管的有益影响已被充分证明,然而,运动改善糖尿病患者血管功能的机制尚不完全清楚。本研究探讨了(1)在8周的中等强度运动(MIE)干预后,雄性UC Davis 2型糖尿病(UCD-T2DM)大鼠的血压和内皮依赖性血管松弛(EDV)是否有改善,(2)内皮源性松弛因子(EDRF)在调节系膜动脉反应性中的相对贡献是否有改变。暴露于药物抑制剂前后测定乙酰胆碱(ACh)的EDV。测定对苯肾上腺素和肌原性张力的收缩反应。同时检测血管内皮一氧化氮(NO)合成酶(eNOS)、环氧化酶(COX)和钙活化钾通道(KCa)的表达。T2DM显著损害EDV,增加收缩反应和肌张力。EDV损伤伴随着NO和COX重要性的升高,而前列腺素和NO非依赖性(内皮源性超极化,EDH)松弛的贡献与对照组相比不明显。MIE 1)增强了EDV,同时降低了收缩反应、肌原性张力和收缩压(SBP), 2)导致糖尿病动脉从对COX的依赖转向对EDH的更大依赖。我们通过改变EDRF在雄性UCD-T2DM大鼠肠系膜动脉舒张中的重要性,首次提供了MIE有益作用的证据。
The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric oxide (NO) synthase (eNOS), cyclooxygenase (COX), and calcium-activated potassium channel (KCa) channels were also measured. T2DM significantly impaired EDV, increased contractile responses and myogenic tone. The impairment of EDV was accompanied by elevated NO and COX importance, whereas the contribution of prostanoid- and NO-independent (endothelium-derived hyperpolarization, EDH) relaxation was not apparent compared to controls. MIE 1) enhanced EDV, while it reduced contractile responses, myogenic tone and systolic blood pressure (SBP), and 2) caused a shift away from a reliance on COX toward a greater reliance on EDH in diabetic arteries. We provide the first evidence of the beneficial effects of MIE via the altered importance of EDRF in mesenteric arterial relaxation in male UCD-T2DM rats.
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