Cardiac remodeling after long-term stimulation by antibodies against the alpha1-adrenergic receptor in rats

Clin Immunol. 2005 Feb;114(2):164-73. doi: 10.1016/j.clim.2004.09.011.

Abstract

Although autoantibodies against the alpha1-adrenergic receptor which had been found in hypertensive patients had agonist-like activity as phenylephrine, the effects of these antibodies on cardiac remodeling have not been known. In this paper, the models with agonist-like activity of antibodies to alpha1-adrenergic receptor were made by immunized Wistar rats using synthesized peptides of alpha1A-adrenergic receptor and raised for 1 year, and the excited antibodies against the alpha1-adrenergic receptor which could elevate the free Ca2+ in isolated adult rat cardiomyocytes had been existed throughout the experiments after immunization. In immunized rats, despite that systolic blood pressure (SBP) had no difference with normal control, the hypertrophy of heart and cardiomyocytes was observed, the collagen deposition in heart interstitium increased, and c-jun expression and matrix metalloproteinase (MMP)-2 mRNA expression and activity in heart had increased. The results suggested that antibodies against the alpha1-adrenergic receptor could induce cardiac remodeling and maybe play a particular role in hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Antagonists / pharmacology
  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology*
  • Calcium / metabolism
  • Collagen / immunology
  • Hypertension / immunology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Molecular Sequence Data
  • Myocardium / immunology*
  • Myocardium / ultrastructure
  • Myocytes, Cardiac / immunology
  • Myocytes, Cardiac / metabolism
  • Peptide Fragments / immunology*
  • Prazosin / pharmacology
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / immunology
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / immunology
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / biosynthesis
  • Receptors, Adrenergic, alpha-1 / immunology*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Antagonists
  • Antibodies
  • Peptide Fragments
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Receptors, Adrenergic, alpha-1
  • Collagen
  • Matrix Metalloproteinase 2
  • Calcium
  • Prazosin