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Evidence for intraventricular secretion of angiotensinogen and angiotensin by the subfornical organ using transgenic mice. Am J Physiol Regul Integr Comp Physiol 2017 06 01;312(6):R973-R981

Date

05/12/2017

Pubmed ID

28490451

Pubmed Central ID

PMC5495920

DOI

10.1152/ajpregu.00511.2016

Scopus ID

2-s2.0-85020436522   8 Citations

Abstract

Direct intracerebroventricular injection of angiotensin II (ANG II) causes increases in blood pressure and salt and water intake, presumably mimicking an effect mediated by an endogenous mechanism. The subfornical organ (SFO) is a potential source of cerebrospinal fluid (CSF), ANG I, and ANG II, and thus we hypothesized that the SFO has a secretory function. Endogenous levels of angiotensinogen (AGT) and renin are very low in the brain. We therefore examined the immunohistochemical localization of angiotensin peptides and AGT in the SFO, and AGT in the CSF in two transgenic models that overexpress either human AGT (A+ mice), or both human AGT (hAGT) and human renin (SRA mice) in the brain. Measurements were made at baseline and following volumetric depletion of CSF. Ultrastructural analysis with immunoelectron microscopy revealed that superficially located ANG I/ANG II and AGT immunoreactive cells in the SFO were vacuolated and opened directly into the ventricle. Withdrawal of CSF produced an increase in AGT in the CSF that was accompanied by a large decline in AGT immunoreactivity within SFO cells. Our data provide support for the hypothesis that the SFO is a secretory organ that releases AGT and possibly ANG I/ANG II into the ventricle at least under conditions when genes that control the renin-angiotensin system are overexpressed in mice.

Author List

Agassandian K, Grobe JL, Liu X, Agassandian M, Thompson AP, Sigmund CD, Cassell MD

Authors

Justin L. Grobe PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensin I
Angiotensin II
Angiotensinogen
Animals
Cerebral Ventricles
Genotype
Humans
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Renin
Renin-Angiotensin System
Subfornical Organ
Time Factors
Up-Regulation