Attenuation of Hypertension by Systemic Delivery of Retroviral Vector Containing Type I Angiotensin II Receptor Antisense cDNA

Despite recent strides in the traditional pharmacological therapies in the control and management of hypertension, a successful prevention and cure for this disease by conventional drug strategy remain at a standstill. We have begun to investigate the conceptual possibility of the use of gene therap...

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Bibliographic Details
Published in:Methods (San Diego, Calif.) Calif.), 2000-11, Vol.22 (3), p.211-218
Main Authors: Reaves, Phyllis Y., Wang, Hong-wei, Katovich, Michael J., Gelband, Craig H., Raizada, Mohan K.
Format: Article
Language:English
Subjects:
3T3 Cells
Angiotensin Receptor Antagonists
Animals
Base Sequence
Blood Pressure
Cell Line
DNA Primers - genetics
DNA, Antisense - administration & dosage
DNA, Antisense - genetics
DNA, Antisense - therapeutic use
Genetic Therapy - methods
Genetic Vectors
Heart - physiopathology
hypertension
Hypertension - genetics
Hypertension - physiopathology
Hypertension - therapy
Mice
Moloney murine leukemia virus - genetics
Rats
Rats, Inbred SHR
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin - genetics
retroviral vector
spontaneously hypertensive rat
systemic delivery
Transfection
Type I angiotensin II receptor antisense
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Summary:Despite recent strides in the traditional pharmacological therapies in the control and management of hypertension, a successful prevention and cure for this disease by conventional drug strategy remain at a standstill. We have begun to investigate the conceptual possibility of the use of gene therapy in the control of hypertension. In this article we describe an experimental protocol that provides proof of the principle that antisense (AS) inhibition of Type I angiotensin II receptor (AT1-R) could prevent development of hypertension on a long-term basis. A retrovirus-based vector has been used to deliver AT1R–AS with high efficiency that attenuates development of high blood pressure and hypertension-associated cardiac and vascular pathophysiology in the spontaneously hypertensive rat.
ISSN:1046-2023
1095-9130
DOI:10.1006/meth.2000.1072