Brain sodium channels and central sodium-induced increases in brain ouabain-like compound and blood pressure

Objective To assess the role of benzamil-sensitive sodium channels in the increases in brain ouabain-like compounds (OLC) and in blood pressure by cerebrospinal fluid (CSF) Na+. Methods Artificial CSF (aCSF) or Na(+-)rich (0-8 mol/l Na+) aCSF, either alone or combined with benzamil (at 1.2 and 4.0 mug/kg per h), were infused intracerebroventricularly (i.c.v.) at 5 mul/h to Wistar rats for 14 days and the effects on the brain and peripheral OLC and blood pressure were studied. OLC content was measured by enzyme-linked immunosorbent assay. Results In Wistar rats infused I.c.v. with aCSF, benzamil did not affect blood pressure or brain and peripheral OLC concentrations. I.c.v. infusion of Na+-rich aCSF increased systolic blood pressure (140 +/- 4 mmHg compared with 119 3 mmHg; P<0.05). Benzamil fully blocked this increase. Na+-rich aCSF increased hypothalamic (23 +/- 3 ng/g tissue compared with 10 +/- 1 ng/g tissue; P< 0.05) and pituitary (233 35 ng/g tissue compared with 62 +/- 7 ng/g tissue; P< 0.05) contents of OLC. In contrast, Na+-rich aCSF decreased OLC in the adrenal gland (7 +/- 1 ng/g tissue compared with 21 +/- 3 ng/g tissue; P < 0.05) and plasma (0.5 +/- 0.04 ng/ml compared with 0.7 +/- 0.08 ng/ml; P< 0.05). Benzamil inhibited these responses of OLC to CSF sodium in a dose-related manner. Conclusions These findings suggest that benzamil-sensitive brain sodium channels mediate the increase in brain OLC and the subsequent hypertension induced by increased CSF Na+. (C) 2003 Lippincott Williams Wilkins.