Angiotensin AT Receptors Expressed in Vasopressin-producing Cells of the Supraoptic Nucleus Contribute to Osmotic Control of Vasopressin

Angiotensin II (ANG) stimulates the release of arginine vasopressin (AVP) from the neurohypophysis through activation of the AT receptor within the brain, although it remains unclear whether AT receptors expressed on AVP-expressing neurons directly mediate this control. We explored the hypothesis that ANG acts through AT receptors expressed directly on AVP-producing cells to regulate AVP secretion. In situ hybridization and transgenic mice demonstrated localization of AVP and AT mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN), but coexpression of both AVP and AT mRNA was only observed in the SON. Mice harboring a conditional allele for the gene encoding the AT receptor (AT) were then crossed with AVP-Cre mice to generate mice that lack AT in all cells that express the AVP gene (AT). AT mice exhibited spontaneously increased plasma and serum osmolality but no changes in fluid or salt-intake behaviors, hematocrit, or total body water. AT mice exhibited reduced AVP secretion (estimated by measurement of copeptin) in response to osmotic stimuli such as acute hypertonic saline loading and in response to chronic intracerebroventricular ANG infusion. However, the effects of these receptors on AVP release were masked by complex stimuli such as overnight dehydration and DOCA-salt treatment, which simultaneously induce osmotic, volemic, and pressor stresses. Collectively, these data support the expression of AT in AVP-producing cells of the SON but not the PVN, and a role for AT receptors in these cells in the osmotic regulation of AVP secretion.