Swimming exercise inhibits myocardial ER stress in the hearts of aged mice by enhancing cGMP‑PKG signaling

Mol Med Rep. 2020 Feb;21(2):549-556. doi: 10.3892/mmr.2019.10864. Epub 2019 Dec 5.

Abstract

The purpose of the present study was to explore aging‑associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4‑month‑old male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stress‑related protein PKR‑like ER kinase, glucose‑regulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP‑specific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated age‑induced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with age‑induced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMP‑protein kinase G signaling.

Keywords: aged; er stress; cardiac function; cGMP; exercise.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Down-Regulation
  • Endoplasmic Reticulum Stress*
  • Male
  • Mice, Inbred C57BL
  • Myocardium / pathology*
  • Physical Conditioning, Animal*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Swimming / physiology*

Substances

  • Reactive Oxygen Species
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP