Selective Silencing of Angiotensin Receptor Subtype 1a (AT 1a R) by RNA Interference

Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT 1a -, AT 1b -, and AT 2 -receptors. Because of a high degree of similarity among these G-protein–coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the expression of the AT 1a receptor (AT 1a R) subtype. A dsRNA, AT 1 47, was found to be highly selective and efficient in reducing the levels of AT 1a R subtype. Transfection of AT 1a R-expressing CHO cells with dsRNA AT 1 47 resulted in an 80% decrease in the AT 1a R expression. In contrast, dsRNA AT 1 47 showed no significant effects on both AT 1b R and AT 2 R subtypes. Thus, AT 1 47 provides us with a powerful tool to selectively silence this subtype of receptor to investigate its role in cardiovascular physiology.