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

Gabor A, Leenen FH. Mechanisms mediating sodium-induced pressor responses in the PVN of Dahl rats. Am J Physiol Regul Integr Comp Physiol 301: R1338-R1349, 2011. First published July 27, 2011; doi: 10.1152/ajpregu.00246.2011.-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 N-omega-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.