Increases in CSF [[Na.sup.+]] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet

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(WKY) rats, at 5-6 wk of age, a cannula was placed in the cisterna magna, and cerebrospinal fluid (CSF) was withdrawn continuously at 75 [micro]l/12 h. CSF was collected as day- and nighttime samples from rats on a regular salt intake (0.6% [Na.sup.+]; R-Na) and then on a high salt intake (8% [Na.sup.+]; 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.sup.+]] 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.sup.+], 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.sup.+] 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.sup.+]]. Finally, in Wistar rats on H-Na, intracerebroventricular infusion of ouabain increased BP and HR but decreased CSF [[Na.sup.+]]. Thus, in both Dahl S and SHR on H-Na, increases in CSF [[Na.sup.+]] preceded the increases in BP and HR, consistent with a primary role of increased CSF [[Na.sup.+]] in the salt-induced hypertension. An increase in brain OLC in response to the initial increase in CSF [[Na.sup.+]] appears to attenuate further increases in CSF [[Na.sup.+]] but at the 'expense' of sympathoexcitation and hypertension. cerebrospinal fluid withdrawal; cisterna magna; [Na.sup.+]-[K.sup.+]-ATPase isoforms; ouabain-like compounds; telemetry