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The potential use of gene therapy in the control of hypertension

M L Gardon1, C H Gelband, M J Katovich

  • 1Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA.

Drugs of Today (Barcelona, Spain : 1998)
|September 16, 2003
PubMed

Insights

Gene therapy targeting the renin-angiotensin system (RAS) offers a novel approach to managing hypertension. Antisense gene delivery to the angiotensin II type 1 receptor (AT1R) effectively controlled blood pressure in rats.

Area of Science:

  • Cardiovascular Research
  • Genetics
  • Pharmacology

Background:

  • Essential hypertension is a progressive disease with unknown etiology, leading to chronically elevated blood pressure.
  • Current antihypertensive treatments, while effective in lowering blood pressure, do not prevent end-organ damage and have significant side effects.
  • The renin-angiotensin system (RAS) plays a crucial role in blood pressure regulation, making it a target for therapeutic intervention.

Purpose of the Study:

  • To provide proof of principle for gene therapy in managing hypertension by genetically interrupting the RAS.
  • To investigate the long-term efficacy of gene therapy in controlling hypertension and reversing associated pathophysiology.
  • To assess the impact of gene therapy on blood pressure, calcium homeostasis, ion channel activity, and cardiovascular ultrastructure.

Main Methods:

  • Delivery of antisense oligonucleotides targeting the angiotensin II type 1 receptor (AT1R) in spontaneously hypertensive rats (SHRs).
  • Comparison of treated SHRs with control rats to evaluate the effects on blood pressure and other physiological parameters.
  • Long-term monitoring of treated animals for up to 18 months to assess sustained therapeutic effects.

Main Results:

  • Antisense gene delivery to AT1R successfully prevented elevated blood pressure in SHRs compared to controls.
  • The treatment also prevented alterations in calcium homeostasis, ion channel activity, and cardiovascular ultrastructure.
  • These beneficial effects were observed for up to 18 months, indicating long-term control.

Conclusions:

  • Antisense gene delivery to AT1R represents a promising strategy for the long-term treatment of hypertension.
  • Gene therapy offers a potential alternative to traditional pharmacological treatments with improved efficacy and reduced side effects.
  • This study demonstrates the feasibility of genetic interruption of the RAS for managing hypertension and its associated complications in animal models.

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