Investigators have produced arteriosclerosis in experimental animals by dietary means for almost half a century. In contrast to the situation in man, however, all previous reports indicate that complicating thrombosis and infarction have been extremely rare in experimental animals. The current report presents dietary regimens by means of which the authors have produced significant numbers of myocardial and renal infarcts in rats (6 of 10 in one group and 4 of 10 in each of 2 others). It is notable that thrombosis occurred before the appearance of severe structural changes in the arterial walls, although abundant fat could often be demonstrated histochemically.
Since Ruyter (1) first described epithelioid cells in the preglomerular arteriole of the kidney, many attempts have been made to elucidate the function of these apparently endocrine "juxtaglomerular cells. ''1 Goormaghtigh (2), from his extensive observations in hypertension and related conditions, postulated that they were probably the source of the vasopressor substance, renin. Among others, Dunihue (3, 4) subscribed to this theory, and his more recent investigations have revealed a relationship between juxtaglomerular cells and the adrenal glands (5). In adrenalectomized animals he found an abnormal increase of secretory granules which could be prevented or reversed by administration of desoxycorticosterone acetate (])CA) (6). A similar increase in granules has also been described by McManus (7) in kidneys from cases of Addison's disease in man. Since DCA is the salt-retaining hormone, these findings suggested to us that the effect of adrenal insufficiency on juxtaglomerular cells might be due primarily to a disturbance in sodium metabolism and that this effect could perhaps be produced by dietary means alone. The current clinical use of diets low in sodium for the treatment of hypertension further stimulated our interest in this possibility.In a preliminary experiment, we were able to demonstrate in the rat, that restriction of dietary sodium chloride for a period of 2 weeks to 1 month caused a striking increase in the numbers of granules in the juxtaglomerular cells. A further series of experiments was then designed to confirm these observations and to determine the effect of variations in the level of dietary sodium chloride with or without DCA administration.
Although much emphasis has been placed on the possible role of juxtaglomerular (JG) 1 cells in hypertension (1), in more recent years it has been discovered that these endocrine-like cells also responded to a disturbance in hormone balance. Dunihue observed a profound increase in JG cells and their granule content in untreated adrenalectomized animals (2, 3) and later found that this effect was prevented or reversed by desoxycorficosterone acetate (DCA) s (4). As previously reported, we were able to produce corresponding changes in JG cells in the intact rat by dietary means alone (5). Salt restriction, like adrenalectomy, caused a striking increase in the granules of JG cells, whereas excessive intake of salt (2 per cent saline in drinking water) produced degranulafion (confirmed by Toussaint e3 a/. (6)). Injections of DCA also degranulated JG cells but the degree of this effect was dearly proportional to the amount of salt ingested. It was concluded that the influence of the adrenal on JG cells was secondary to disturbances in salt metabolism. Although this interpretation has been challenged (7), subsequent investigation has supported our concept, as well as further elucidating the relation of juxtaglomerular cells to the adrenal gland.In the present investigation, changes in juxtaglomerular cells were found to be closely related to alterations in the zona glomerulosa, but not to other zones, of the adrenal cortex. These findings will be interpreted on the basis of the evidence provided by Deane eta/. (8) that the zona glomerulosa is responsible for the electrolyte-regulating function of the adrenal cortex. MethodsAnimals and Experimental Procedures.~A total of 159 albino rats of the Wistar strain from five experiments involving low, normal, and high salt intake, with or without additional
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