Angiotensin Type 1 Receptors in the Subfornical Organ Mediate the Drinking and Hypothalamic-Pituitary-Adrenal Response to Systemic Isoproterenol

Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT(1)Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT(1)Rs that bind bloodborne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT(1)Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT(1)R [AT(1)R antisense (AT(1)R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT(1)R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT(1)R binding in other nuclei. Subsequently, water intake, ACTH, and corticosterone (CORT) were assessed after administration of isoproterenol, a beta-adrenergic agonist that decreases blood pressure and elevates circulating ANGII. Delivery of AT(1)R AS into the SFO attenuated water intake, ACTH, and CORT after isoproterenol, whereas similar treatment in the OVLT had no effect. To determine the specificity of this blunted drinking and HPA response, the same parameters were measured after treatment with hypertonic saline, a stimulus that induces drinking independently of ANGII. Delivery of AT(1)R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT(1)R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII. (Endocrinology 149: 6416-6424, 2008)