Mechanisms in the PVN mediating local and central sodium-induced hypertension in Wistar rats.

Sympathoexcitatory and hypertensive responses to central infusion of Na(+)-rich artificial cerebrospinal fluid (aCSF) are enhanced by aldosterone and mediated by mineralocorticoid receptors (MRs) and benzamil-blockable Na(+) influx, leading to "ouabain" release and ANG II type 1 (AT(1)) receptor stimulation. The present study evaluated the functional role of these mechanisms in the paraventricular nucleus (PVN). In conscious Wistar rats, Na(+)-rich aCSF was infused either directly into the PVN or intracerebroventricularly preceded by aldosterone and blockers. Infusion of Na(+)-rich aCSF in the PVN caused gradual increases in blood pressure (BP) and heart rate (HR). Aldosterone and a subpressor dose of ouabain in the PVN alone did not affect BP and HR but enhanced responses to Na(+). Eplerenone, benzamil, and "ouabain"-binding Fab fragments only blocked the enhancement by aldosterone, whereas losartan blocked all responses to Na(+)-rich aCSF in the PVN. Increases in BP and HR by intracerebroventricular infusion of Na(+)-rich aCSF were enhanced by aldosterone infused intracerebroventricularly, but not in the PVN. Telmisartan in the PVN again blocked all responses. In contrast, both eplerenone and benzamil in the PVN did not change the pressor responses to intracerebroventricular infusion of aldosterone and Na(+)-rich aCSF. These findings indicate that AT(1) receptors in the PVN mediate the responses to Na(+)-rich aCSF and their enhancement by aldosterone, both locally in the PVN or in the general CSF. MRs, benzamil-blockable Na(+) channels or transporters, and "ouabain" can be functionally active in the PVN, but in Wistar rats appear not to contribute to the pressor responses to short-term increases in CSF [Na(+)].