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(Hypertension. 2001;37:357.)
© 2001 American Heart Association, Inc.

State-of-the-Art Lecture

The Future of Hypertension Therapy: Sense, Antisense, or Nonsense?

Alok S. Pachori; Matthew J. Huentelman; Sharon C. Francis; Craig H. Gelband; Michael J. Katovich; Mohan K. Raizada

From the Departments of Pharmacodynamics (A.S.P., M.J.K.) and Physiology (M.J.H., S.C.F., C.H.G., M.K.R.), Colleges of Pharmacy and Medicine, and University of Florida, McKnight Brain Institute, Gainesville.

Correspondence to Mohan K. Raizada, PhD, Department of Physiology, Box 100274, College of Medicine, University of Florida, Gainesville, FL 32610. E-mail mraizada{at}phys.med.ufl.edu

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.

Key Words: renin-angiotensin system • genes • rats, spontaneously hypertensive • hypertension, genetic • antisense elements