Handling ²² NaCl by the Blood-Brain Barrier and Kidney

Abstract

Abstract-We previously reported that inappropriate renal vasoconstriction in Dahl salt-sensitive (DS) rats fed high NaCl diets may cause sodium retention. The present study examined the distribution and elimination of 22 Na in DS and Dahl salt-resistant (DR) rats, and we determined whether an abnormality in renal function might also cause sodium retention in DS rats. Following an intravenous bolus of 4 Ci 22 NaCl in prehypertensive DS and DR rats with similar blood pressures on low (0.23%) or high (8% for 4 days) NaCl diets, urinary clearance of 22 Na in 1 hour was about 4 times less in DS than DR rats, and renal retention of 22 Na was up to 8 times greater in DS than DR rats (PϽ0.01), suggesting that a renal functional defect may contribute to salt retention in DS rats; however, its uptake in tail artery, heart, lungs, liver, and spleen was similar in DS and DR rats. Uptake in brain was up to 5 times greater in DS than DR rats (PϽ0.01). Cerebrospinal fluid 22 Na radioactivity (in counts per minute) revealed that the blood-brain barrier is 5 to 8 times more permeable to sodium in DS than DR rats (PϽ0.01). Cerebrospinal fluid volume and brain water content increased significantly (PϽ0.01) in DS but not DR rats on an 8% NaCl diet. Intracerebroventricular bolus injection of 0.06 mL of 4.5 mol/L NaCl acutely and transiently induced the same degree of hypertension in DR and DS rats, whereas similar volume injections of isotonic saline, 4.5 mol/L Na-acetate, or 4.5 mol/L NaBr did not produce hypertension in either strain. We conclude that functional abnormalities in DS rat kidneys may cause retention of NaCl and that an increased blood-brain barrier permeability to NaCl may enhance its access to sites in the brain that are then activated and induce hypertension. T he mechanism of NaCl-induced hypertension in Dahl salt-sensitive (DS) rats and in salt-sensitive humans is unclear. Yet considerable evidence suggests that the renal abnormality that causes blood pressure (BP) elevation in acquired and inherited hypertension may be associated with a diminished sodium excretion. 1,2 The cause of renal hemodynamic and/or functional abnormalities in DS rats that might play a role in the development of salt-sensitive hypertension is unknown; however, a number of biochemical derangements that might impair renal function have been implicated, including deficiency in the generation of cyclic GMP, 3 20-hydroxyeicosatetraenoic acid, 4 kallikrein, 5 prostaglandin E 2 , 6 or dopamine. 7 It has also been postulated that hypertension develops in DS rats because of a decrease in nitric oxide production. 8,9 DS rats appear to have a genetic functional derangement in the kidney that causes salt retention 10 rather than a deficit of nephrons that Brenner et al [11][12][13] postulated as a cause of hypertension. Although evidence suggests that sodium chloride (NaCl) is retained by kidneys of DS rats, 14 -17 accumulation of sodium in blood or tissues has not been conclusively demonstrated.The DS rat is an excellent animal model for study of th...

Plasma sodium and hypertension

“…These observations suggest that a rise in plasma sodium may have an exaggerated effect on the sodium concentration of those areas surrounding the third ventricle, which control the blood pressure [61]. In the Dahl S and R rats placed on a high sodium diet, the rise in blood pressure in the Dahl S rat is associated with a substantially greater accumulation of 22 Na + in the CSF and brain of the Dahl S rat [62].…”

The Role of Cardiotonic Steroids in the Pathogenesis of Cardiomyopathy in Chronic Kidney Disease

“…Specifically, high salt intake elevates both plasma and cerebrospinal fluid Na + [71,72], and this induces the secretion of CTS by the adrenals and the hypothalamus. Intracerebroventricular infusion of Na + -rich cerebrospinal fluid [73] or ouabain [71] increased sympathetic nerve activity, heart rate and blood pressure in rodents, and these effects were partially reversed by Digibind®.…”

High salt-diet reduces SLC14A1 gene expression in the choroid plexus of Dahl salt sensitive rats

“…Data from the present study (Figure 2) demonstrate that the [Na + ] in the CSF was significantly increased in Dahl S rats after 2-week high salt diet treatment. This phenomenon has also been observed in spontaneously hypertensive rats [19]. The rise in CSF [Na + ] may directly or indirectly stimulate neuronal activity in brain cardiovascular regulatory regions, leading to sympathoexcitation and blood pressure elevation [20.…”

“…High salt intake increases sodium concentration [Na + ] in the cerebrospinal fluid (CSF) in Dahl S rats and spontaneously hypertensive rats (SHR), whereas CSF sodium shows minimal changes in Dahl salt-resistant (Dahl R) and Wistar-Kyoto (WKY) rats [6, 7]. Elevated CSF Na + may increase neuronal activity in the CNS, sequentially leading to over-activation of the sympathetic nervous system.…”