Attenuation of hypertension by systemic delivery of retroviral vector containing type I angiotensin II receptor antisense cDNA

Despite recent strides in the traditional pharmacological therapies in the control and management of hypertension, a successful prevention and cure fo r this disease by conventional drug strategy remain at a standstill. We hav e begun to investigate the conceptual possibility of the use of gene therap y in the control of hypertension. In this article we describe an experiment al protocol that provides proof of the principle that antisense (AS) inhibi tion of Type I angiotensin II receptor (AT(1)-R) could prevent development of hypertension on a longterm basis. A retrovirus-based vector has been use d to deliver AT(1)R-AS with high efficiency that attenuates development of high blood pressure and hypertension-associated cardiac and Vascular pathop hysiology in the spontaneously hypertensive rat. (C) 2000 Academic Press.