RNA Silencing In Vivo Reveals Role of p22phox in Rat Angiotensin Slow Pressor Response

The angiotensin II (Ang II) slow-pressor response entails an increase in mean arterial pressure and reactive oxygen species. We used double-stranded interfering RNAs (siRNAs) in Sprague Dawley rats in vivo to test the hypothesis that an increase in the p22 component of NADPH oxidase is required for this response. Reactive oxygen species were assessed from excretion of 8-isoprostane prostaglandin F2α and blood pressure by telemetry. Two siRNA sequences to p22 (sip22) reduced mRNA >85% in cultured vascular smooth muscle cells. Rats received rapid (10 second) IV injections (50 to 100 μg) of 1 of 2 different sip22, control siRNA, or vehicle (TransIt in saline) during 14 day SC infusions of Ang II (200 ng · kg · min) or sham infusions. In both groups, sip22, relative to control siRNA, led to significant (P