Mechanisms mediating sodium-induced pressor responses in the PVN of Dahl rats

Abstract

Intracerebroventricular infusion of Na+-rich artificial cerebrospinal fluid (aCSF) causes larger sympathetic and pressor responses in Dahl salt-sensitive (S) than -resistant (R) or Wistar rats. Enhanced activity of the aldosterone-“ouabain” pathway or decreased nitric oxide (NO) release may contribute to this enhanced responsiveness. Where in the brain these mechanisms interact is largely unknown. The present study evaluated whether Na+ in the paraventricular nucleus (PVN) causes larger pressor responses in Dahl S (SS/Mcw) than R (Dahl SS.BN13) rats and whether mineralocorticoid receptors, benzamil-blockable Na+ channels, “ouabain,” angiotensin type 1 receptors, or NO mediates these enhanced responses. Na+-rich aCSF in the PVN caused 30–40% larger increases in blood pressure and heart rate in Dahl S than R or Wistar rats, whereas responses to ouabain, ANG II, or Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) in the PVN were the same. These responses to Na+ were not affected by eplerenone, benzamil, or Fab fragments, whereas they were fully blocked by losartan, in Dahl S and R rats. l-NAME enhanced them more in Dahl R than S rats, thereby equalizing the responses in the two strains. Pressor responses to l-NAME in the PVN were attenuated by a high-salt diet in Dahl S, but not R, rats. The results indicate that acute and chronic increases in Na+ concentration in the PVN inhibit NO release in the PVN of Dahl S, but not R, rats, thereby contributing to the enhanced pressor responses to Na+ in Dahl S rats.