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 microg/kg per h), were infused intracerebroventricularly (i.c.v.) at 5 microl/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+.
Wang
Hao
H
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Leenen
Frans H H
FH
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002298:Cardenolides; D004077:Digoxin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000378:metabolism*; D012964:Sodium / Q000134:cerebrospinal fluid; D015222:Sodium Channels / Q000378:metabolism*
D002298:Cardenolides; D012503:Saponins; D015222:Sodium Channels; C034504:digoxin-like factors; C013407:benzamil; D004077:Digoxin; D000584:Amiloride; D012964:Sodium