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 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 (AT(1)-R) could prevent development of hypertension on a long-term basis. A retrovirus-based vector has been used to deliver AT(1)R-AS with high efficiency that attenuates development of high blood pressure and hypertension-associated cardiac and vascular pathophysiology in the spontaneously hypertensive rat.
Reaves
P Y
PY
Department of Physiology, University of Florida Brain Institute, Gainesville, Florida 32610, USA.
Wang
H W
HW
Katovich
M J
MJ
Gelband
C H
CH
Raizada
M K
MK
D016475:3T3 Cells; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D016373:DNA, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D014162:Transfection
D057911:Angiotensin Receptor Antagonists; D017931:DNA Primers; D016373:DNA, Antisense; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin