Angiotensin type 1 receptors in the subfornical organ mediate the drinking and hypothalamic-pituitary-adrenal response to systemic isoproterenol

Endocrinology. 2008 Dec;149(12):6416-24. doi: 10.1210/en.2008-0477. Epub 2008 Aug 7.


Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT1Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT1Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT1R [AT1R antisense (AT1R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT1R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT1R 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 AT1R 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 AT1R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT1R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenocorticotropic Hormone / blood
  • Angiotensin II / metabolism
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Corticosterone / blood
  • Drinking / drug effects*
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Hypothalamus / physiology
  • Isoproterenol / pharmacology*
  • Male
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiology
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Receptor, Angiotensin, Type 1 / physiology
  • Sodium Chloride / pharmacology
  • Subfornical Organ / drug effects*
  • Subfornical Organ / metabolism
  • Subfornical Organ / physiology


  • Adrenergic beta-Agonists
  • Angiotensin II Type 1 Receptor Blockers
  • Oligodeoxyribonucleotides, Antisense
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • Sodium Chloride
  • Adrenocorticotropic Hormone
  • Isoproterenol
  • Corticosterone