title: Increases in CSF [Na+] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet.
abstract: In Dahl salt-sensitive (S) and salt-resistant (R) rats, and spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, at 5-6 wk of age, a cannula was placed in the cisterna magna, and cerebrospinal fluid (CSF) was withdrawn continuously at 75 microl/12 h. CSF was collected as day- and nighttime samples from rats on a regular salt intake (0.6% Na+; R-Na) and then on a high salt intake (8% Na+; H-Na). In separate groups of rats, the abdominal aorta was cannulated and blood pressure (BP) and heart rate (HR) measured at 10 AM and 10 PM, with rats first on R-Na and then on H-Na. On H-Na, CSF [Na+] started to increase in the daytime of day 2 in Dahl S rats and of day 3 in SHR. BP and HR did not rise until day 3 in Dahl S rats and day 4 in SHR. In Dahl R and WKY rats, high salt did not change CSF [Na+], BP, or HR. In a third set of Dahl S rats, sampling of both CSF and BP was performed in each individual rat. Again, significant increases in CSF [Na+] were observed 1-2 days earlier than the increases in BP and HR. In a fourth set of Dahl S rats, BP and HR were recorded continuously by means of radiotelemetry for 5 days on R-Na and 8 days on H-Na. On H-Na, BP (but not HR) increased first in the nighttime of day 2. In another set of Dahl S rats, intracerebroventricular infusion of antibody Fab fragments binding ouabain-like compounds (OLC) with high affinity prevented the increase in BP and HR by H-Na but further increased CSF [Na+]. Finally, in Wistar rats on H-Na, intracerebroventricular infusion of ouabain increased BP and HR but decreased CSF [Na+]. Thus, in both Dahl S and SHR on H-Na, increases in CSF [Na+] preceded the increases in BP and HR, consistent with a primary role of increased CSF [Na+] in the salt-induced hypertension. An increase in brain OLC in response to the initial increase in CSF [Na+] appears to attenuate further increases in CSF [Na+] but at the "expense" of sympathoexcitation and hypertension.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Van Vliet
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002298:Cardenolides; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004077:Digoxin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009994:Osmolar Concentration; D010042:Ouabain / Q000008:administration & dosage; D051381:Rats; D020303:Rats, Inbred Dahl / Q000134:cerebrospinal fluid / Q000502:physiology*; D011918:Rats, Inbred SHR / Q000134:cerebrospinal fluid / Q000502:physiology*; D012503:Saponins / Q000378:metabolism; D012964:Sodium / Q000134:cerebrospinal fluid*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013686:Telemetry
chemical_list: D002298:Cardenolides; D002316:Cardiotonic Agents; D007140:Immunoglobulin Fab Fragments; D012503:Saponins; D017673:Sodium Chloride, Dietary; C034504:digoxin-like factors; D010042:Ouabain; D004077:Digoxin; D012964:Sodium