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Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension

M L Fu1, H Herlitz, W Schulze

  • 1Wallenberg Laboratory, Sahlgren's Hospital, University of Göteborg, Sweden.

Journal of Hypertension
|August 10, 2000
PubMed

Insights

Autoantibodies against the angiotensin II receptor (AT1) were found in patients with malignant hypertension, suggesting a role in the disease's development. These autoantibodies target a functional part of the AT1 receptor.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Hypertension Pathophysiology

Background:

  • Malignant hypertension is a severe form of hypertension with high mortality.
  • The role of autoantibodies in the pathogenesis of hypertension is not fully understood.
  • G-protein-coupled receptors are crucial in cardiovascular regulation.

Purpose of the Study:

  • To investigate the presence of autoantibodies against cardiovascular G-protein-coupled receptors in patients with malignant hypertension.
  • To determine if autoantibodies against angiotensin II receptor (AT1), bradykinin (B2), or angiotensin II subtype 2 (AT2) receptors are associated with malignant hypertension.
  • To assess the functional activity of identified autoantibodies.

Main Methods:

  • Sera from patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases, and healthy controls were analyzed.
  • Enzyme immunoassay was used to detect autoantibodies against AT1, B2, and AT2 receptors.
  • Sensitivity of the assay was determined.
  • Affinity-purified autoantibodies were used to localize AT receptors and assess their effect on cardiomyocytes.

Main Results:

  • Autoantibodies against the AT1 receptor were detected in 14% of patients with malignant essential hypertension and 33% with malignant secondary hypertension.
  • No antibodies against B2 or AT2 receptors were found in any patient group.
  • Purified autoantibodies from positive patients localized AT receptors and induced a positive chronotropic effect on neonatal rat cardiomyocytes.

Conclusions:

  • Autoantibodies against a functional extracellular domain of human AT1 receptors exist in patients with malignant hypertension.
  • These autoantibodies may play a role in the pathogenesis of malignant hypertension.
  • Further research is warranted to elucidate the precise mechanisms involved.

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