Angiotensin type 1 receptor antisense in the subfornical organ attenuates the drinking and corticosterone response to isoproterenol

Antisense (AS) oligodeoxynulceotides are single-stranded DNA molecules that are used to inhibit the expression of targeted genes. In this study we used AS oligodeoxynulceotides directed against angiotensin type 1 receptors (AT1R) to inhibit expression of these receptors within specific circumventricular organs. Subsequently, we evaluated the contribution of these AT1R to water intake and corticosterone release after hypotension. Rats were stereotaxically implanted with guide cannulae terminating in the subfornical organ (SFO) or the organum vasculosum of the lamina terminalis (OVLT) and given a week to recover. Cannulae placement was confirmed by measuring water intake after injection of angiotensin II or 1 M NaCl into the SFO or OVLT respectively. One week later, AT1R AS or scrambled oligonucleotides (scram) were injected into the SFO or OVLT for three consecutive days. Three hours after the last injection, rats were treated with isoproterenol, given water, and intake was measured every 15 min for 2 h. To evaluate the contribution of AT1R to hypotension-induced corticosterone secretion rats were treated as previously described. However, after administration of isoproterenol rats were not given water, but instead were placed in restrainers and tail blood samples were taken at 0, 15, 30, 60 and 120 min.Administration of AT1R AS into the OVLT had no effect on isoproterenol-induced water intake or corticosterone secretion. In contrast, AT1R AS administered into the SFO attenuated the drinking and corticosterone responses to isoproterenol. These results suggest that AT1R within the SFO mediate drinking and corticosterone responses to hypotension. Support DK4806110 and DK6659603.