RNA Silencing In Vivo Reveals Role of p22 super(phox) 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 super(phox) component of NADPH oxidase is required for this response. Reactive oxygen species were assessed from excretion of 8-isoprostane prostaglandin F sub(2 alpha ) and blood pressure by telemetry. Two siRNA sequences to p22 super(phox) (sip22 super(phox)) reduced mRNA >85% in cultured vascular smooth muscle cells. Rats received rapid (10 second) IV injections (50 to 100 mu g) of 1 of 2 different sip22 super(phox), control siRNA, or vehicle (TransIt in saline) during 14 day SC infusions of Ang II (200 ng . kg super(-1) . min super(-1)) or sham infusions. In both groups, sip22 super(phox), relative to control siRNA, led to significant (P