Voluntary running counteracts right ventricular adverse remodeling and myocyte contraction impairment in pulmonary arterial hypertension model

Life Sci. 2019 Dec 1:238:116974. doi: 10.1016/j.lfs.2019.116974. Epub 2019 Oct 19.

Abstract

Aim: Analyze the effects of voluntary running during the development of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) on the right ventricle (RV) structure, RV myocyte contractility and intracellular Ca2+ transient in rats with MCT-induced PAH.

Main methods: Male Wistar rats were housed sedentary or with free access to a running wheel after MCT or saline injection for until HF or median end-point day of HF in sedentary animals (24 days). Echocardiographic examination and exercise tolerance test were carried out at specific time points of the experimental period. After euthanasia, the heart was dissected, weighed and processed for either histological or single myocyte contractility and intracellular Ca2+ transient analyzes.

Key findings: Voluntary running delayed the onset of HF (29 days) and the increase in pulmonary artery resistance, and improved exercise tolerance. In the median end-point day of HF, exercise retarded RV adverse remodeling (i.e. increase in extracellular matrix and collagen content). At this stage, exercise also delayed impairments in cell contractile function (i.e. amplitude and times to peak and to half relaxation) and intracellular calcium cycling (i.e. amplitude and times to peak and to half decay) in RV single myocytes.

Significance: Along with HF onset delay and physical effort tolerance enhancement, voluntary running during the development of PAH postpones pulmonary artery resistance increases, RV adverse remodeling and myocyte contractility and intracellular calcium cycling deterioration in rats. Therefore, self-paced intermittent exercise of high intensity may contribute positively to the health and survival of individuals with PAH.

Keywords: Calcium transient; Collagen; Exercise tolerance; Pulmonary hypertension.

MeSH terms

  • Animals
  • Calcium
  • Disease Models, Animal
  • Heart Failure / etiology
  • Heart Failure / pathology
  • Heart Failure / prevention & control*
  • Hypertension, Pulmonary / complications*
  • Hypertrophy, Right Ventricular / etiology
  • Hypertrophy, Right Ventricular / pathology
  • Hypertrophy, Right Ventricular / prevention & control*
  • Male
  • Muscle Contraction*
  • Myocytes, Cardiac / pathology*
  • Physical Conditioning, Animal*
  • Pulmonary Artery / pathology*
  • Rats
  • Rats, Wistar
  • Running
  • Ventricular Remodeling*

Substances

  • Calcium