Chronic Sodium Chloride Toxicity in the Albino Rat

Abstract

The need for common salt in the diet is an ancient, inveterate cognition, deeply rooted in human mores, to such an extent that little thought has been given to the chronic toxicity of sodium chloride. A search of the literature reveals a number of papers which describe toxic effects of sodium chloride in fowl (1), but a paucity of information relative to mammals. Campbell (2) reported the possibility of kidney damage in the rat fed a diet containing more than 5 per cent of sodium chloride. Mosier (3) studied the adrenal glands in rats on diets very high in sodium chloride. Sapirstein, Brandt, and Drury (4) and Gross (5) produced hypertension in rats fed diets high in sodium chloride and restricted in the amount of fluid. This was accomplished by substituting saline solution for drinking water. Binet, Dejours, and Lacaisse (6) raised rats on a high sodium chloride regimen and described a resulting renal hypertrophy and functional adaptation. A few experiments of a chronic nature have been made using the mouse (7), the albino and the kangaroo rat (8), the dog (9), and the cow (10).Recently Meneely, Tucker, and Darby (11) reported on the growth of rats fed for 20 weeks on purified diets containing seven different levels of sodium chloride. The present paper describes certain pathologic manifestations of chronic sodium chloride toxicity which were observed in these animals. Abstracts of these findings have appeared (12). Materials and MethodsThe experimental regimen has been described (11). Male, albino, Sprague-Dawley rats, weighing an average of 119 gm., were placed on purified rations and demineralized water ad libitum. The purified rations contained seven different levds of sodium chloride as follow: ration I (low Na diet), about 0.01 per cent Nat1; ration II (control diet), 0.15 per cent NaCI; ration III, 2.8 per cent NaCI; ration IV, 5.6 per cent NaC1; ration V, 7.0 per cent NaCI; ra-71

The time course of salt-induced hypertension, and why it matters

“…[65][66][67] In their experiments, the effects of dietary salt were investigated in more than 600 male outbred (Sprague-Dawley) rats followed over their lifespan (up to 30 months). Although many levels of dietary salt were investigated, results obtained for a moderately high salt (2.8% NaCl) diet and control (0.15% NaCl) diet are of particular relevance.…”

“…The 2.8% NaCl diet was considered to be roughly comparable with a 14 g NaCl (240 mmol Na) intake in humans (assuming a 500 g dry weight daily food intake). [65][66][67] Such an intake is above the average sodium intake in Western societies but nevertheless corresponds with the normal level of sodium intakes in many individuals (for example, it corresponds with the sodium intake of X5% of the American population as a whole and with the intake of B25% of young American male individuals 18 ). Using the same assumptions, the 0.15% NaCl control diet corresponds with a 0.75 g NaCl (13 mmol Na) intake; that is, within the range of levels found in huntergatherer societies.…”

“…Bottom: responses of individual rats at 12 months of high salt exposure. Reproduced (with minor modification) from Meneely et al 66 with permission (copyright 1953, The Rockefeller University Press).…”

Age as a function in the development of sodium-related hypertension.

“…In man the evidence is indirect (36,(40)(41)(42)(43)(44)(45)(46)(47)(48), but in the laboratory animal the evidence is direct and unequivocal (25)(26)(27)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61). The extensive research with rat, chicken, rabbit, dog, and monkey models may be summarized as follows: (1) the greater the ingestion of salt, the more severe the hypertension; (2) the younger the animal at the time it is fed a high salt diet, the more sensitive it is to developing rapid hypertension; (3) even a brief exposure (2-6 weeks) to a high salt intake early in life may influence the later development of permanently elevated BP; (4) genetic factors influence the individual's response to salt (NaCl) intake.…”

A 5-component mathematical model for salt-induced hypertension in Dahl-S and Dahl-R rats

“…Salt intake has often been linked to the development of hypertension [3][4][5] and the BP response to salt has been studied in chimpanzees [6], spider monkeys [7], rats [8,9], mice [10] and humans [11]. Until recently, salt-induced hypertension was viewed as a single event and different time courses of the development of hypertension were not distinguished.…”