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The treatment and prevention of hypertension has been a worldwide medical challenge. The key pathological hallmark of hypertension is altered arterial vascular structure and function, i.e., increased peripheral vascular resistance due to vascular remodeling. The aim of this review is to elucidate the molecular mechanisms of vascular remodeling in hypertension and the protective mechanisms of aerobic exercise against vascular remodeling during the pathological process of hypertension. The main focus is on the mechanisms of oxidative stress and inflammation in the pathological condition of hypertension and vascular phenotypic transformation induced by the trilaminar structure of vascular endothelial cells, smooth muscle cells and extracellular matrix, and the peripheral adipose layer of the vasculature. To further explore the possible mechanisms by which aerobic exercise ameliorates vascular remodeling in the pathological process of hypertension through anti-proliferative, anti-inflammatory, antioxidant and thus inhibiting vascular phenotypic transformation. It provides a new perspective to reveal the intervention targets of vascular remodeling for the prevention and treatment of hypertension and its complications. [ABSTRACT FROM AUTHOR]

Aerobic exercise increases M2AChR, which thus improves cardiac function in cardiovascular disease (CVD) rats. This study aimed to determine whether aerobic exercise could ameliorate pressure overload‐induced heart hypertrophy through M2AChR, and to elucidate the underlying mechanisms of action. Mice were used to establish the myocardial hypertrophy model by transverse aortic constriction (TAC), and subjected to 2, 4, and 8 weeks of moderate‐intensity aerobic exercise and choline intervention (14 mg/kg/day). Our results showed that 4 and 8 weeks of exercise and choline intervention reduced excessive mitochondrial fission and autophagy of myocardial mitochondria, thereby improving the ultrastructure and function of mitochondria after TAC. Moreover, 8‐week exercise and choline intervention have enhanced parasympathetic function and promoted the expression of M2AChR. In addition, 8‐week exercise and choline intervention also inhibited the protein expression of myocardial MFN2, PERK/eIF2α/ATF4, and NLRP3/caspase‐1/IL‐1β signaling pathways, thereby effectively reducing mitochondrial fusion, endoplasmic reticulum stress, and inflammation. Taken together, these data suggest that pressure overload led to cardiac hypertrophy, cardiac dysfunction, and decreased parasympathetic function in cardiac tissues. Aerobic exercise attenuated cardiac dysfunction by modulating the expression of proteins involved in mitochondrial quality control, and induced endoplasmic reticulum stress and inflammation, thereby reducing cardiac hypertrophy and improving cardiac function in impaired heart tissues following TAC, which was likely mediated by M2AChR activation. [ABSTRACT FROM AUTHOR]

Aims: Adaptive changes in the heart by exercise have been shown to reduce the risk of cardiovascular disease, and M2 Acetylcholine receptor (M2AChR), a receptor abundantly present on cardiac parasympathetic nerves, is closely associated with the development of cardiovascular disease. The present study intends to investigate whether exercise can regulate endoplasmic reticulum stress (ERS) and mitophagy through M2AChR to resist myocardial ischemia-reperfusion (I/R) injury and to elucidate its mechanism of action. Results: Exercise enhanced parasympathetic nerve function and increased myocardial M2AChR protein expression in I/R rats. In addition, it promoted the protein expression of MFN2 and inhibited the expression of Drp1, Chop, PINK1/Parkin, and PERK/eIF2α/ATF4 signaling pathways, effectively reducing mitophagy, ERS, and apoptosis. At the cellular level, 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced hypoxia/reoxygenation (H/R)-induced ERS through the downregulated expression of PERK/eIF2α/ATF4 pathway proteins in H9C2 cardiomyocytes. When intervened with M2AChR inhibitors, the levels of ERS and phosphorylation levels of the PERK/eIF2α/ATF4 pathway were increased in H/R cells. Innovation and Conclusion: Exercise intervention activated the parasympathetic state in rats. It inhibited myocardial mitophagy and ERS levels, and reduced myocardial apoptosis through M2AChR, thereby resisting I/R-induced myocardial injury and improving cardiac function. Antioxid. Redox Signal. 40, 209–221. [ABSTRACT FROM AUTHOR]