The future of hypertension therapy: sense, antisense, or nonsense?
Hypertension is a debilitating disease with significant socioeconomic and emotional impact. Despite recent success in the development of traditional pharmacotherapy for the management of hypertension, the incidence of this disease is on the rise and has reached epidemic proportions by all estimates. This has led many to conclude that traditional pharmacotherapy has reached an intellectual plateau, and novel approaches for the treatment and control of hypertension must be explored. We have begun to investigate the possibility of treating and/or curing hypertension by using genetic means. In this review, we will provide evidence in favor of targeting of the renin-angiotensin system by antisense gene therapy as an effective strategy for the lifelong prevention of hypertension in the spontaneously hypertensive rat model. In addition, we will discuss the properties of an ideal vector for the systemic delivery of genes and the potential experimental hurdles that must be overcome to take this innovative approach to the next level of evaluation.
Department of Pharmacodynamics Colleges of Pharmacy and Medicine, and University of Florida, McKnight Brain Institute, Gainesville, USA.
A S
AS
Pachori
M J
MJ
Huentelman
S C
SC
Francis
C H
CH
Gelband
M J
MJ
Katovich
M K
MK
Raizada
D000256:Adenoviridae / Q000235:genetics; D053607:Adrenomedullin; D000804:Angiotensin II; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure; D016373:DNA, Antisense / Q000008:administration & dosage; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006678:HIV / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*; D007610:Kallikreins / Q000235:genetics; D008164:Luminescent Proteins; D009154:Mutation; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D010455:Peptides / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
D016373:DNA, Antisense; D008164:Luminescent Proteins; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007610:Kallikreins