Volume 14, Issue 3, Pages 213-220 (December 2007) Endogenous brain Na pumps, brain ouabain-like substance and the α2 isoform in salt- dependent hypertension  James W. Van Huysse  Pathophysiology  Volume 14, Issue 3, Pages 213-220 (December 2007) DOI: 10.1016/j.pathophys.2007.09.010 Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Putative mechanisms of the secretion of sodium into the CSF involving the brain Na, K-ATPase. A choroid plexus blood vessel is shown within a brain ventricle. (A) Enlarged cross-section of the vessel. (B) Enlargement of an epithelial cell within the wall of (A), showing both lumenal and CSF sides. Step 1. Sodium from the lumen (blood) enters the cell via epithelial sodium channels (ENaC). Step 2. Na is transported from the cytosol out of the cell into the CSF by the Na, K-ATPase (NKA). Pathophysiology 2007 14, 213-220DOI: (10.1016/j.pathophys.2007.09.010) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 Proposed regulation of brain OLS production and OLS actions. A schematic of the brain ventricular system is shown containing cerebrospinal fluid (CSF) and surrounded by brain tissue. (A) Enlargement of the area inside the white box, which represents an ependymal cell that lines a cerebral ventricle. 1. Sodium from the interstitial fluid (ISF) enters the cell via epithelial sodium channels (ENaC). Once inside the cell, Na can either trigger the production of the brain ouabain-like substance (OLS, Step 2) or can be transported into the CSF via the Na, K-ATPase (NKA, Step 3). The OLS in turn can be secreted into the CSF (Step 4), where it can feed back to regulate CSF [Na] by inhibiting NKA. (B) Pathway of synthesis/activity of OLS produced in neurons that are distant from the ventricle. Na enters the neuron from the ISF via ENaC as in (A) (Step 1), stimulating the production of the OLS (Step 2). The OLS is then transported through axons, is released and causes an excitatory effect at downstream synapses (Step 3). Ultimately the pathway activates brain angiotensinergic neurons that increase sympathetic nervous system (SNS) activity (Step 4) and raise blood pressure (Step 5). Adapted from the hypothesis of Huang et al. [52,59]. Pathophysiology 2007 14, 213-220DOI: (10.1016/j.pathophys.2007.09.010) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions