Ahmed Amer, Fusi Fabio, Valoti Massimo
Dipartimento di Scienze della Vita, Università di Siena, via A. Moro 2, 53100 Siena, Italy.
Dipartimento di Biotecnologie, Chimica e Farmacia, Università di Siena, via A. Moro 2, 53100 Siena, Italy.
Pharmacol Res. 2022 Jun;180:106231. doi: 10.1016/j.phrs.2022.106231. Epub 2022 Apr 21.
Several studies demonstrate the beneficial effects of dietary flavonoids on the cardiovascular system. Since perivascular adipose tissue (PVAT) plays an active role in the regulation of vascular tone in both health and diseases, the present study aimed to assess the functional interaction between PVAT and flavonoids in vitro on rat aorta rings. Several flavonoids proved to display both antispasmodic and spasmolytic activities towards noradrenaline-induced contraction of rings deprived of PVAT (-PVAT). However, on PVAT-intact (+PVAT) rings, both actions of some flavonoids were lost and/or much decreased. In rings-PVAT, the superoxide donor pyrogallol mimicked the effect of PVAT, while in rings+PVAT the antioxidant mito-tempol restored both activities of the two most representative flavonoids, namely apigenin and chrysin. The Rho-kinase inhibitor fasudil, or apigenin and chrysin concentration-dependently relaxed the vessel active tone induced by the Rho-kinase activator NaF; the presence of PVAT counteracted apigenin spasmolytic activity, though only in the absence of mito-tempol. Similar results were obtained in rings pre-contracted by phenylephrine. Finally, when β receptors were blocked by SR59230A, vasorelaxation caused by both flavonoids was unaffected by PVAT. These data are consistent with the hypothesis that both noradrenaline and apigenin activated adipocyte β receptors with the ensuing release of mitochondrial superoxide anion, which once diffused toward myocytes, counteracted flavonoid vasorelaxant activity. This phenomenon might limit the beneficial health effects of dietary flavonoids in patients affected by either obesity and/or other pathological conditions characterized by sympathetic nerve overactivity.
多项研究证明了膳食类黄酮对心血管系统的有益作用。由于血管周围脂肪组织（PVAT）在健康和疾病状态下对血管张力的调节中均发挥着积极作用，本研究旨在体外评估PVAT与类黄酮在大鼠主动脉环上的功能相互作用。几种类黄酮被证明对去PVAT（-PVAT）环由去甲肾上腺素诱导的收缩具有抗痉挛和解痉活性。然而，在完整PVAT（+PVAT）环上，一些类黄酮的这两种作用均丧失和/或大幅减弱。在-PVAT环中，超氧化物供体邻苯三酚模拟了PVAT的作用，而在+PVAT环中，抗氧化剂线粒体靶向性Tempol恢复了两种最具代表性类黄酮（即芹菜素和白杨素）的活性。Rho激酶抑制剂法舒地尔，或芹菜素和白杨素能浓度依赖性地舒张由Rho激酶激活剂NaF诱导的血管主动张力；PVAT的存在抵消了芹菜素的解痉活性，不过仅在不存在线粒体靶向性Tempol的情况下。在用去氧肾上腺素预收缩的环中也获得了类似结果。最后，当β受体被SR59230A阻断时，两种类黄酮引起的血管舒张不受PVAT影响。这些数据与以下假设一致，即去甲肾上腺素和芹菜素均激活脂肪细胞β受体，随之释放线粒体超氧阴离子，一旦其扩散至心肌细胞，就会抵消类黄酮的血管舒张活性。这种现象可能会限制膳食类黄酮对肥胖症患者和/或以交感神经活动过度为特征的其他病理状况患者的有益健康作用。
