The potential use of gene therapy in the control of hypertension.
Essential hypertension is a progressive disease characterized by chronically elevated blood pressure of unknown etiology. Because antihypertensive treatments cannot be aimed at a specific cause, traditional pharmacological therapy targets elements such as the renin-angiotensin system (RAS), that are known to be directly involved in the control of blood pressure. Current pharmacological treatment effectively lowers blood pressure but may not prevent end organ damage or propensity for other disease or death and has other significant disadvantages such as unpleasant side effects. The development of gene therapy directed at RAS is a significant advance toward managing high blood pressure associated with hypertension and reversing its associated pathophysiology. It was our intent to provide "proof of principle" for gene therapy by the interruption of RAS at the genetic level in order to achieve long-term control of hypertension and reverse the pathophysiology associated with this disease. In general, delivery of antisense to the angiotensin II type 1 receptor (AT1R) successfully prevented blood pressure elevation, alterations in calcium homeostasis, ion channel activity and cardiovascular ultrastructure changes for up to 18 months in spontaneously hypertensive rats (SHRs) when compared to control rats. These results demonstrate that antisense gene delivery is useful in the long-term treatment of hypertension in animal models.
Gardon
M L
ML
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA.
Gelband
C H
CH
Katovich
M J
MJ
Raizada
M K
MK