Glial angiotensinogen regulates brain angiotensin II receptors in transgenic rats TGR (ASrAOGEN)

J Monti, M Schinke, M Böhm… - American Journal …, 2001 - journals.physiology.org
J Monti, M Schinke, M Böhm, D Ganten, M Bader, G Bricca
American Journal of Physiology-Regulatory, Integrative and …, 2001journals.physiology.org
TGR (ASrAOGEN) 680, a newly developed transgenic rat line with specific downregulation
of astroglial synthesis of angiotensinogen, exhibits decreased brain angiotensinogen
content associated with a mild diabetes insipidus and lower blood pressure.
Autoradiographic experiments were performed on TGR (ASrAOGEN)(TG) and Sprague-
Dawley (SD) control rats to quantify AT1 and AT2 receptor-binding sites in different brain
nuclei and circumventricular organs. Dose-response curves for drinking response to …
TGR(ASrAOGEN)680, a newly developed transgenic rat line with specific downregulation of astroglial synthesis of angiotensinogen, exhibits decreased brain angiotensinogen content associated with a mild diabetes insipidus and lower blood pressure. Autoradiographic experiments were performed on TGR(ASrAOGEN) (TG) and Sprague-Dawley (SD) control rats to quantify AT1 and AT2 receptor-binding sites in different brain nuclei and circumventricular organs. Dose-response curves for drinking response to intracerebroventricular injections of ANG II were compared between SD and TG rats.
In most of the regions inside the blood-brain barrier [paraventricular nucleus (PVN), piriform cortex, lateral olfactory tract (LOT), and lateral preoptic area (LPO)], AT1 receptor binding (sensitive to CV-11974) was significantly higher in TG compared with SD. In contrast, in the circumventricular organs investigated [subfornical organ (SFO) and area postrema], AT1 receptor binding was significantly lower in TG. AT2 receptors (binding sensitive to PD-123319) were detected at similar levels in the inferior olive (IO) of both strains. Angiotensin-binding sites sensitive to both CV-11974 and PD-123319 were detected in the LPO of SD rats and specifically upregulated in LOT, IO, and most notably PVN and SFO of TG. The dose-response curve for water intake after intracerebroventricular injections showed a higher sensitivity to ANG II of TG (EC50 = 3.1 ng) compared with SD (EC50 = 11.2 ng), strongly suggesting that the upregulation of AT1 receptors inside the blood-brain barrier of TG rats is functional.
Finally, we showed that downregulation of angiotensinogen synthesized by astroglial cells differentially regulates angiotensin receptor subtypes inside the brain and in circumventricular organs.
American Physiological Society