Effects of chronic intraventricular sodium on blood pressure and fluid balance.

Abstract

To examine if chronic sodium loading on the brain produces sustained increases in blood pressure, water intake, and sodium excretion, hypertonic (0.5 M and 1.5 M) and isotonic (0.15 M) NaCI solutions were infused into the third ventricle of Sprague-Dawley rats at a rate of 5.5 Itl/hr for 7 days. Intracerebroventricular infusion of 1.5 M NaCI significantly increased systolic blood pressure during the entire infusion period (+23±5 mm Hg on day 1 and +15±2 mm Hg on day 7, n=10, mean±SEM). Blood pressure rose insignificantly in the 0.5 M NaCI group, whereas it remained at the baseline levels in the 0.15 M NaCI group. The increases in water intake (day 2), positive water balance (day 2), and negative sodium balance (day 3) were observed in the 1.5 M NaCI group. On day 7, the 1.5 M NaCI group showed hyponatremia and low plasma osmolality and had higher plasma norepinephrine but not vasopressin compared with the 0.15 M NaCI group. In another series of study, depressor response to intravenous hexamethonium (20 mg/kg) in the 1.5 M NaCI group was greater than that in the 0.15 M NaCI group on both day 1 and 7. The depressor response to </(CH2) 5 These events are accompanied by various neurohormonal changes such as stimulation of the sympathetic nervous system with suppression of the renal nerve activity, release of vasopressin, sodium pump inhibitor and atrial natriuretic factor, stimulation of the pituitary-adrenocortical axis, and suppression of the peripheral reninangiotensin system. 1 ' 35 -8 Both the sympathetic nervous system and vasopressin appear to mediate the pressor response to intracerebroventricularly administered hypertonic NaCI.3 59The central action of sodium might play an important role in the relation between salt and hypertension. The sympathetic nervous system and vasopressin may participate in several models

Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats

“…Other mechanisms such as vasopressin and marinobufagenin (8) may play a role as well. However, in Sprague-Dawley rats intracerebroventricular infusion of hypertonic saline for 7 days increased CSF [Na ϩ ] by 5 mmol/l and resting BP by ϳ15 mmHg, but plasma vasopressin remained normal and did not contribute to the chronic elevation of BP (25). Body fluid volumes and urinary excretion of water and electrolytes were not measured, but body weights, plasma electrolytes and hematocrit did not differ significantly among rats on the different treatments, making sodium and water retention less likely.…”

“…Blockade of brain OLC prevents intracerebroventricular aldosterone-induced sympathetic hyperactivity and hypertension (40). Increasing CSF [Na ϩ ] by intracerebroventricular infusion of Na ϩ -rich artificial CSF (aCSF) elicits sympathoexcitatory and pressor responses in a number of rat strains (21,22,25,38). In Wistar rats, sympathoexcitatory and pressor responses to Na ϩ -rich CSF can be prevented by CNS blockade of OLC or AT 1 -receptors (21), whereas CNS blockade of ENaC (by benzamil) prevents the increase in brain OLC as well as the sympathetic excitation and hypertension (42).…”

Responses to Central Na + and Ouabain Are Attenuated in Transgenic Rats Deficient in Brain Angiotensinogen

“…2,3 Similar changes in these parameters are observed in normotensive rats with chronic central Na ϩ loading. 4,5 With high salt intake, salt-sensitive rats develop sympathetic hyperactivity and hypertension, possibly because of higher CSF Na ϩ concentrations 12 as well as higher responsiveness for a given increase in CSF Na ϩ , as suggested by responses to shortterm 6,13 or long-term 14 ICV infusions of hypertonic saline. This sodium-induced sympathetic hyperactivity and hypertension can be prevented by blockade of brain AT 1 receptors with losartan, 2,5 or blockade of brain "ouabain."…”

“…2,3 These central effects of high salt can be prevented by blockade of ouabainlike activity ("ouabain") 2,3 or the renin-angiotensin system (RAS) 2 in the brain. Salt-induced sympathoexcitation and hypertension in salt-sensitive rats can be mimicked in normotensive rats by central sodium loading, 4,5 which can also be prevented by blockade of "ouabain" or angiotensin (Ang) II type 1 (AT 1 ) receptors in the brain. 5 These findings support the concept that in salt-sensitive rats receiving high salt, increased sodium in the cerebrospinal fluid (CSF) activates central pathways involving "ouabain" and AT 1 -receptors, causing sympathoexcitation and hypertension.…”

“…6 Thus far, central administration of AT 1 -receptor antagonists such as losartan has been used to assess the role of the RAS in the brain in salt-sensitive hypertension. 2,5 This approach has its limitations: (1) the antagonists will block brain AT 1 receptors both inside and outside the blood-brain barrier and therefore do not differentiate between central effects of circulating versus locally produced Ang II; and (2) AT 1 -receptor blockade can lead to unopposed, even enhanced stimulation of other Ang II receptors such as AT 2 and AT 4 . These limitations may lead to overestimation of the role of a local brain RAS and brain AT 1 receptors in salt-sensitive hypertension.…”