Gazi University, Faculty of Pharmacy, Department of Pharmacology, Etiler, 06330 Ankara, Turkey.
Karamanoglu Mehmetbey University, K.Ö. Faculty of Science, Department of Biology, Karaman 70100, Turkey.
Life Sci. 2022 May 1;296:120424. doi: 10.1016/j.lfs.2022.120424. Epub 2022 Feb 20.
Hypertension is one of the major causes of cardiac damage. In this study, the effects of resveratrol supplementation and regular exercise on hypertension-induced cellular stress responses of myocardium were compared.
Hypertension was induced in male Wistar rats by deoxycorticosterone-acetate + salt administration for 12 weeks. Resveratrol and regular exercise were applied for the last six weeks. In addition to biochemical and molecular examinations, isoprenaline, phenylephrine and, acetylcholine-mediated contractions and sinus rate were recorded in the isolated cardiac tissues.
Resveratrol and regular exercise reduced systolic blood pressure in hypertensive rats. The altered adrenergic and cholinergic responses of the right atrium and left papillary muscles in hypertension were separately improved by resveratrol and regular exercise. Resveratrol and regular exercise decreased plasma and cardiac total antioxidant capacity and, augmented the expression of antioxidant genes in hypertensive rats. While regular exercise restored the increase in p-PERK expression associated with endoplasmic reticulum stress and decrease in mitophagic marker PINK1 expression, resveratrol only ameliorated PINK1 expression in hypertensive rats. Resveratrol and exercise training suppressed hypertension-induced NLRP3 inflammasome activation by reversing the increase in NLRP3, p-NF-κB expression and the mature-IL-1β/pro-IL-1β and cleaved-caspase-1/pro-caspase-1 ratio. Resveratrol and exercise enhanced mRNA expression of caspase-3, bax, and bcl-2 involved in the apoptotic pathway, but attenuated phosphorylation of stress-related mitogenic proteins p38 and JNK induced by hypertension.
Our study demonstrated the protective effect of resveratrol and exercise on hypertension-induced cardiac dysfunction by modulating cellular stress responses including oxidative stress, ER stress, mitophagy, NLRP3 inflammasome-mediated inflammation, and mitogenic activation.
高血压是心脏损伤的主要原因之一。本研究比较了白藜芦醇补充和规律运动对高血压引起的心肌细胞应激反应的影响。
通过给予去氧皮质酮乙酸盐+盐 12 周诱导雄性 Wistar 大鼠高血压。在最后六周应用白藜芦醇和规律运动。除了生化和分子检查外，还记录了分离的心脏组织中异丙肾上腺素、苯肾上腺素和乙酰胆碱介导的收缩和窦率。
白藜芦醇和规律运动降低了高血压大鼠的收缩压。白藜芦醇和规律运动分别改善了高血压大鼠右心房和左乳头肌改变的肾上腺素能和胆碱能反应。白藜芦醇和规律运动降低了高血压大鼠的血浆和心脏总抗氧化能力，并增加了抗氧化基因的表达。虽然规律运动恢复了与内质网应激相关的 p-PERK 表达增加和促凋亡标志物 PINK1 表达减少，但白藜芦醇仅改善了高血压大鼠的 PINK1 表达。白藜芦醇和运动训练通过逆转 NLRP3、p-NF-κB 表达和成熟-IL-1β/pro-IL-1β 和 cleaved-caspase-1/pro-caspase-1 比值的增加，抑制了高血压引起的 NLRP3 炎性小体激活。白藜芦醇和运动增强了 caspase-3、bax 和 bcl-2 参与凋亡途径的 mRNA 表达，但减轻了高血压诱导的应激相关有丝分裂原蛋白 p38 和 JNK 的磷酸化。
本研究表明，白藜芦醇和运动通过调节细胞应激反应，包括氧化应激、内质网应激、线粒体自噬、NLRP3 炎性小体介导的炎症和有丝分裂原激活，对高血压引起的心脏功能障碍具有保护作用。
