Studies on the Role(s) of Cerebrospinal Fluid Osmolality and Chloride Ion in the Centrally Mediated Pressor Responses of Sodium Chloride

Abstract

These studies were designed to investigate whether the centrally mediated pressor effects of hypertonic sodium chloride (NaCl) solutions are triggered in response to changes in the cerebrospinal fluid (CSF) osmolality and whether the chloride ion plays a role in these effects. In Inactin anesthetized, vagotomized rats, alterations in the arterial pressure to cerebroventricular administration (i.c.v.) of various concentrations of NaCl, sodium nitrate (NaNO3), glycerol, creatinine, lithium chloride (LiCl), lithium nitrate (LiNO3) and choline chloride were evaluated. The pressor effects of NaCl were significantly greater than those produced by either glycerol, creatinine and/or NaNO3 solutions. Central effects of NaCl were identical to that of LiCl; likewise, NaNO3 and LiNO3 produced essentially similar increases in the blood pressure. In other words, the two chloride salts produced significantly greater increases in the arterial pressure than the nitrate salts. Choline chloride also produced significant increases in the blood pressure both before and after pretreatment with hemicholinum (i.c.v.). In a separate series of experiments, pretreatment of rats with a vasopressin antagonist (i.v.), significantly attenuated the pressor effects of NaCl, NaNO3 and that of choline chloride whereas after autonomic ganglionic blockade with chlorisondamine, pressor responses of only NaCl, but not those of NaNO3 or choline chloride were significantly inhibited. These data indicate that elevation of either Na+ or Cl- in the CSF facilitates vasopressin secretion and that Na+ and Cl- ions function synergistically in the central nervous system (C.N.S.) to enhance sympathetic activity. The present studies demonstrate that the circumventricular structures in the C.N.S. that participate in the regulation of blood pressure are more responsive to changes in concentrations of Na+ and Cl- rather than to net changes in the CSF osmolality. The data further suggest that the chloride ion contributes to the central pressor effects of NaCl and may play a role in the pathophysiology of salt-dependent hypertension.