Intracerebroventricular Administration of AT1 Receptor Antisense Oligonucleotides Inhibits the Behavioral Actions of Angiotensin II

Antisense oligonucleotides were developed to study the expression and function of angiotensin type 1 (AT1) receptors in cultured cells and brain. In both liver epithelial WB and neuroblastoma N1E-115 cells AT1 antisense oligomers substantially decreased AT1 receptor density, whereas angiotensin type 2 (AT2) receptors remained unchanged. Similarly, repeated intracerebroventricular injections of AT1 antisense oligomers in rats decreased AT1 receptor density in hypothalamic-thalamic-septal tissue, and AT2 receptors were unaffected. Intracerebroventricular antisense oligomers also attenuated drinking elicited by intracerebroventricular angiotensin II but not the cholinomimetic carbachol. Collectively, these results demonstrate that antisense oligonucleotides attenuate angiotensin receptor expression and function in behaving animals.