Retrovirally mediated delivery of angiotensin II type 1 receptor antisense in vitro and in vivo.
In spite of excellent drugs that are available for the control of hypertension, the pharmacological approach has major disadvantages including compliance, side effects, and inability to cure the disease. In the present chapter we provide evidence that a gene therapy concept based on the inhibition of the RAS at a genetic level, with the use of an antisense to the AT1R, is an exciting and viable approach for long-term control of hypertension without the disadvantages inherent in pharmaceutical therapy. A retrovirus-based vector has been used to deliver AT1R-AS in Ang II target tissues both in vitro and in vivo. The transduction efficiency is high and leads to the attenuation of Ang II action in vitro and prevention of hypertension in the SH rat, a model for primary human hypertension. These studies have unveiled a new avenue in which a similar approach could be attempted in the reversal of hypertension in adult animals.
Wang
H
H
Department of Physiology, University of Florida College of Medicine, Gainesville 32610, USA.
Lu
D
D
Reaves
P Y
PY
Katovich
M J
MJ
Raizada
M K
MK
D000818:Animals; D016373:DNA, Antisense / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005822:Genetic Vectors; D006973:Hypertension / Q000188:drug therapy*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012190:Retroviridae
D016373:DNA, Antisense; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin