Inability to induce hypertension in normotensive rat expressing AT(1) receptor antisense

Our previous studies have shown that neonatal delivery of angiotensin type 1 receptor antisense (AT(1)R-AS) in a retroviral vector prevents spontaneou sly hypertensive rats from developing hypertension for life but has no effe ct on blood pressure (BP) in normotensive animals. Based on these results, we hypothesized that AT(1)R-AS transduction in normotensive rats would prot ect them from developing experimental hypertension. The present study was d esigned to evaluate this hypothesis. A single intracardiac administration o f AT(1)R-AS by a retroviral-mediated delivery system (LNSV-AT(1)R-AS) in 5- day-old normotensive Sprague-Dawley rats resulted in long-term expression o f the AT(1)R-AS without an effect on basal BP. However, angiotensin II (Ang II)-induced BP, dipsogenic responses, and renovascular contractility were significantly attenuated in the LNSV-AT(1)R-AS-treated rats. Chronic infusi on of low-dose Ang II (55 ng . kg(-1) . min(-1)) in LNSV-alone-treated rats caused a modest increase in BP, profound increase in cardiac hypertrophy, and increased vascular contractility. In contrast, the LNSV-AT(1)R-AS-treat ed rats were protected from developing these changes after Ang II infusion. These data establish that LNSV-AT(1)R-AS pretreatment protects healthy rat s from developing Ang II-dependent hypertension.