Enhanced sympathoexcitatory and pressor responses to central Na+ in Dahl salt-sensitive vs. -resistant rats

An enhanced responsiveness to increases in cerebrospinal fluid (CSF) Na+ by high salt intake may contribute to salt-sensitive hypertension in Dahl sal t-sensitive (S) rats. To test this hypothesis, sympathetic and pressor resp onses to acute and chronic increases in CSF Na+ were evaluated. In consciou s young (5-6 wk old) and adult (10-11 wk old) Dahl S and salt-resistant (R) rats as well as weight-matched Wistar rats, hemodynamic [blood pressure (B P) and heart rate (HR)] and sympathetic [renal sympathetic nerve activity ( RSNA)] responses to 10-min intracerebroventricular infusions of artificial CSF (aCSF) and Na+-rich aCSF (containing 0.2-0.45 M Na+) were evaluated. In tracerebroventricular Na+-rich aCSF increased BP, RSNA, and HR in a dose-re lated manner. The extent of these increases was significantly larger in Dah l S versus Dahl R or Wistar rats and young versus adult Dahl S rats. In a s econd set of experiments, young Dahl S and R rats received a chronic intrac erebroventricular infusion of aCSF or Na+-rich (0.8 M) aCSF (5 mul/h) for 1 4 days, with the use of osmotic minipumps. On day 14 in conscious rats, CSF was sampled and BP, HR, and RSNA were recorded at rest and in response to air stress, intracerebroventricular alpha (2)-adrenoceptor agonist guanaben z, intracerebroventricular ouabain, and intravenous phenylephrine and nitro prusside to estimate baroreflex function. The infusion of Na+ rich aCSF ver sus aCSF increased CSF Na+ concentration to the same extent but caused seve re versus mild hypertension in Dahl S and Dahl R rats, respectively. After central Na+ loading, hypothalamus "ouabain" significantly increased in Dahl S and only tended to increase in Dahl R rats. Moreover, sympathoexcitatory and pressor responses to intracerebroventricular exogenous ouabain were at tenuated by Na+-rich aCSF to a greater extent in Dahl S versus Dahl R rats. Responses to air-jet stress or intracerebroventricular guanabenz were enha nced by Na+-rich aCSF in both strains, but the extent of enhancement was si gnificantly larger in Dahl S versus Dahl R. Na+-rich aCSF impaired arterial baroreflex control of RSNA more markedly in Dahl S versus R rats. These fi ndings indicate that genetic control of mechanisms linking CSF Na+ with bra in "ouabain" is altered in Dahl S rats toward sympathetic hyperactivity and hypertension.