Hypertension is a complex pathophysiological state that leads to serious co
mplications, including heart failure, coronary artery disease, and abnormal
renal function. While traditional therapies can be effective in controllin
g the effects of hypertension, they offer no long-term cure and often lead
to patient noncompliance, thereby diminishing their effectiveness. These re
asons, coupled with the recent developments in gene transfer and somatic ce
ll gene delivery, led researchers to explore alternative options that can p
roduce long term control of hypertension. Gene therapy offers the potential
to yield lasting antihypertensive effects by influencing the genes associa
ted with hypertension. In this review, we will discuss the merits of sense
versus antisense strategies in controlling hypertension. We also discuss th
e advantages and disadvantages of both viral and nonviral vector types for
the systemic delivery of genes for hypertension research. Results of our re
search group on the retrovirus-mediated delivery of the angiotensin type I
receptor-antisense on the prevention of hypertension and related cardiovasc
ular pathophysiology will be summarized. Finally, we discuss the future of
this gene therapy approach in the reversal and long-term control of hyperte
nsion.