| A high-salt diet raises the sodium concentration in the cerebrospinal fluid (CSF [Na+]) in salt-sensitive individuals, an effect that can be mimicked by intracerebroventricular (icv) infusion of NaCl. Increasing CSF [Na+] increases the concentration of an endogenous brain ouabain-like substance(s) (OLS) that inhibits brain Na, K-ATPases, which in turn activates the brain renin-angiotensin system, augmenting sympathetic nervous system activity and blood pressure. It is unknown which of the ouabain-sensitive Na, K-ATPase alpha subunit isoforms (alpha2 or alpha3) in the brain mediates the pressor responses to increased CSF [Na+]. We hypothesize that the alpha2 isoform mediates the pressor responses to elevated CSF [Na +], such that reduced expression of the alpha2 isoform in mice, via heterozygous gene-targeted knockout, should enhance the pressor response to icv infusion of Na+ or ouabain, compared to wildtype litter mates. These studies suggest a critical role for the alpha2 subunit isoform of the Na, K-ATPase in the pressor response to increased CSF [Na+]. (Abstract shortened by UMI.). |
