Early reversal cardiac with esmolol in hypertensive rats: The role of subcellular organelle phenotype

Pharmacol Rep. 2019 Dec;71(6):1125-1132. doi: 10.1016/j.pharep.2019.06.013. Epub 2019 Jun 29.

Abstract

Background: Our group has previously shown that short-term treatment (48 h) with esmolol reduces left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). However, we do not know the mechanism that explain this effect. The aim of this study was to assess the role that the subcellular organelle phenotype plays in early cardiac reverse after short-term treatment with esmolol.

Methods: 14-Month-old male SHRs were randomly assigned to receive esmolol (300 μg/kg/min) (SHR-E) or vehicle (SHR). Age-matched male Wistar-Kyoto rats (WKY) served as controls. After 48 h of treatment, an ultrastructural analysis of heart tissue (left ventricle) was performed. We studied cardiomyocyte ultrastructural remodeling of subcellular organelles by electronic microcopy in all groups.

Results: SHR group showed significant morphometric and stereological changes in mitochondria and subcellular organelles (cytoplasm and nucleus, myofibril structure, mitochondria structure, Z-Disk, intercalated disk, T-system and cystern), and also changes in the extracellular matrix (collagen) with respect to WKY group. Esmolol significantly improved the morphology and stereology mitochondrial, reduced the organelle phenotype abnormalities but no produced changes in the extracellular matrix with respect to SHR group. Interesantly, parameters of mitochondria (regularity factor, ellipsoidal form factor and density of volume), and all parameters of subcellular organelles returned to the normality in SHR-E.

Conclusion: Our results show that left ventricular hypertrophy reversal after short-term treatment with esmolol is associated with reversal of subcellular organelle phenotype.

Keywords: Cardiac reversal; Endoplasmic reticulum; Esmolol; Mitochondria; T-tubules; Z-disk.

MeSH terms

  • Animals
  • Heart / physiopathology
  • Hypertrophy, Left Ventricular / drug therapy*
  • Hypertrophy, Left Ventricular / physiopathology
  • Myocardium / pathology*
  • Myocardium / ultrastructure*
  • Organelles / pathology*
  • Organelles / ultrastructure*
  • Propanolamines / pharmacology*
  • Rats, Inbred SHR
  • Rats, Inbred WKY

Substances

  • Propanolamines
  • esmolol