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Gene Therapy for Hypertension

Antisense Inhibition of the Renin-Angiotensin System

  • Protocol
Book cover Hypertension

Part of the book series: Methods In Molecular Medicine™ ((MIMM,volume 108))

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Abstract

Despite excellent antihypertensive drugs on the market, about 70% of all hypertensive patients do not have their blood pressure under control. This is due to problems of compliance, largely because of having to take drugs daily and side effects. We propose an antisense therapy for hypertension because antisense treatment can provide long-lasting, highly specific control of blood pressure. Antisense to oligonucleotides can be designed to inhibit genes that produce proteins known to be overactive in hypertension and that are proven targets of current drug treatments. These include β1-receptors, angiotensin-converting enzyme (ACE), and angiotensin type 1 receptors (AT1R). Antisense oligonucleotides are short (12-20 bases), single strands of DNA. They are designed to hybridize to specific mRNA and prevent translation of the target protein. Antisense inhibition of ACE, angiotensinogen or AT1R genes components of the renin-angiotensin system effectively reduce high blood pressure in animal models of hypertension. These include a genetic model (SHR) a surgical model (2KIC), and an environmental model (cold-induced hypertension). In all models, a single systemic administration of antisense decreased blood pressure by about 25 mmHg, and the effect could last up to 1 mo. No toxic effects of repeated antisense treatment were found. The results indicate that antisense therapy could be used for human hypertension and provide long-term protection that would increase compliance of patients.

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Authors and Affiliations

  1. Department of Physiology & Internal Medicine, University of South Florida, Tampa, FL

    M. Ian Phillips

  2. Department of Anthropology, University of Florida, Gainesville, FL

    Birgitta Kimura

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  1. M. Ian Phillips
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  2. Birgitta Kimura
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Editors and Affiliations

  1. Moyne Institute for Preventive Medicine, Trinity College, Dublin, Ireland

    Jérôme P. Fennell

  2. Division of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK

    Andrew H. Baker

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Phillips, M.I., Kimura, B. (2005). Gene Therapy for Hypertension. In: Fennell, J.P., Baker, A.H. (eds) Hypertension. Methods In Molecular Medicine™, vol 108. Humana Press. https://doi.org/10.1385/1-59259-850-1:363

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  • DOI: https://doi.org/10.1385/1-59259-850-1:363

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-323-7

  • Online ISBN: 978-1-59259-850-2

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