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(Hypertension. 1998;32:380-386.)
© 1998 American Heart Association, Inc.

Hypothesis

Transcription-Modulating Drugs

A New Frontier in the Treatment of Essential Hypertension

Theodore W. Kurtz; ; David G. Gardner

From the Departments of Laboratory Medicine (T.W.K.) and Medicine (D.G.G.), University of California at San Francisco.

Abstract

Abstract—While the promises of gene therapy may be years away from realization, the therapeutic use of drugs that act by modifying gene transcription is a well-established practice in clinical medicine. Although transcription-modulating drugs are frequently used in many different specialties, the deliberate development and use of these agents in cardiovascular medicine has been comparatively limited. However, research advances in the area of gene transcription and in the molecular genetic regulation of blood pressure, insulin resistance, lipid metabolism, and cell growth are providing new opportunities for controlling the expression of genes that are relevant to the pathogenesis of cardiovascular disease and essential hypertension. These research advances are beginning to converge in the development of transcription-modulating drugs with the potential to attack genetically determined risk factors that often cluster in patients with essential hypertension. Ligand-activated transcription factors that serve as receptors for small lipophilic compounds such as the thiazolidinediones and retinoids represent examples of potential therapeutic targets with direct effects on the expression of genes relevant to the pathogenesis of essential hypertension and its complications. Mounting evidence suggesting that the superior cardiorenal protective properties of converting enzyme inhibitors are related in part to their ability to indirectly modify the expression of genes in the heart and vasculature provides provisional support for the clinical value of this therapeutic approach. Given the success of transcription-modulating drugs in the treatment of type II diabetes and many other clinical disorders, it is anticipated that these agents will be developed as tools for the prevention and treatment of hypertension and cardiovascular disease in the not too distant future.

Key Words: hypertension, essential • genetics • thiazolidinediones • transcription • drugs • blood pressure • angiotensin

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