The defense of brain volume during hyponatremia cannot be explained by the losses of brain sodium and potassium. We have examined the brain losses of organic osmolytes in rats after 24 h of severe hyponatremia induced by the administration of vasopressin and 5% dextrose in water. Normonatremic controls and animals with intermediate plasma sodium concentration ([Na]) were produced in vasopressin-treated animals by the administration of isocaloric gavages containing varying amounts of NaCl and free water. The animals were killed at 24 h by decapitation, and one brain hemisphere was quickly frozen in liquid nitrogen for organic osmolyte determinations. When compared with controls (plasma [Na] = 139 +/- 1.5 mM), hyponatremic animals (plasma [Na] = 96 +/- 1 mM) had significantly reduced brain contents for sodium, potassium, chloride, glutamate, myo-inositol, N-acetylaspartate, aspartate, creatine, taurine, gamma-aminobutyric acid, and phosphoethanolamine. Plasma [Na] was highly correlated (P < 0.001) with the brain contents for sodium, potassium, and organic osmolytes. Whereas the observed increase in brain water during hyponatremia was only 4.8%, by calculation, brain swelling without brain organic osmolyte losses would have been 11%, an amount that jeopardizes survival.

No abstract

A B S T R A C T Studies of the metabolism of glutamine and glutamate by renal cortex slices from acidotic, alkalotic, and control rats were performed. 88-95% of the glutamine and 104-115% of the glutamate taken up from the medium could be accounted for by the products found. Acidosis increased glutamine uptake and conversion to ammonia, C02, glucose, lactate, pyruvate, lipid, and protein. The increase in glutamine conversion to ammonia after acidosis could be completely accounted for by the associated increase in its conversion to glucose, glutamate, lactate, and pyruvate. When glutamate metabolism was examined, acidosis did not affect substrate uptake but did increase its conversion to ammonia, glucose, lactate, C02, and lipid. The increase in 14CO2 from U-"C-glutamine and U-`4C-glutamate found with cortex slices from acidotic animals could be explained by the C02 production calculated to be associated with the enhanced conversion of these substrates to other products during acidosis. 'CO2 production from 1,2-"C-acetate was found to be significantly increased in alkalosis rather than acidosis. These studies suggest that in the rat, the rate at which glutamine is completely oxidized in the Krebs cycle is not a factor regulating renal ammonia production. A comparison of the effects of acidbase status on glutamine and glutamate metabolism suggests that either glutamine transport or glutamine transaminase activity are significantly increased by acidosis. Mr. Strope is a second year student at

In a recent study (1), we confirmed the observation of Bresler (2) and Toussaint and Vereerstraeten (3) that tubular sodium reabsorption (TNa) in dogs increases following plasma sodium (PNa) elevation. However, when the increase in filtered sodium (FNa) that usually accompanied an elevated PNa was eliminated by reducing glomerular filtration rate (GFR) with an aortic clamp, hypernatremia appeared to inhibit rather than stimulate TNa. Similar results have been obtained by Blythe and Welt (4), who found that sodium excretion during the infusion of hypertonic saline was above control when filtered sodium was reduced below control by inflating a balloon in the inferior vena cava. The micropuncture studies of Giebisch, Klose, and Windhager (5) in rats have also demonstrated that TNa is decreased by hypertonic saline infusions.In all these studies the depression of TNa was considered to be a consequence of hypernatremia per se. In each case, hypernatremia was induced by loading with hypertonic saline. The infusion of similar volumes of isotonic saline has been shown to inhibit TNa to a comparable degree (6-9). Therefore, the studies cited do not clearly differentiate between volume expansion and hypernatremia as the cause of the decreased TNa, nor, indeed, do they clearly establish that hyper-