Production of Renal-Cardiovascular Disease in Adrenalectomized Rats: Crane, Baker and Ingle11 have demonstrated renal-cardiovascular changes in adrenalectomized rats exposed to cold. All the rats were uninephrectomized and ate a 4 per cent salt diet ad libitum. Adrenalectomized rats were treated with maintenance doses of adrenal cortical extract. Groups of adrenalectomized and nonadrenalectomized rats were each subdivided into groups which were adapted to low temperature and kept at 3 to 5 C. for 60 days; similar groups were kept at room temperature for the same period of time. When the rats were exposed to cold, the gross and microscopic damage to hearts and kidneys was equally marked in adrenalectomized and in nonadrenalectomized rats. The role of the adrenal glands in causing the disorders which occurred in the cold-exposed rats is uncertain for two reasons. Food intake was not constant. The animals exposed to cold ate more of the high salt diet than did controls at room temperature. Second, the amount of adrenal cortical extract (4 cc./rat/day) used for replacement therapy was associated with some increase in renal-cardiovascular disease when the comparison was made with nonadrenalectomized rats at room temperature.

Large doses of methylandrostenediol (MAD) cause severe hypertension with cardiovascular-renal damage in the salt-loaded uninephrectomized rat. Such animals develop edema when fed a 4 per cent sodium chloride diet by stomach tube, thereby indicating sodium-retaining effects of this synthetic steroid. Adrenalectomy protects the rat against the damaging effects of MAD; but when adrenalectomized, uninephrectomized, salt-loaded rats are maintained on small doses of adrenal cortical extract, the administration of MAD causes hypertension and renal-myocardial damage12 quite as severe as can be produced in the presence of the adrenal glands.

Renal Hypertension: Hypertension can be caused by damage to the kidneys in either experimental animals or in man. Grollman13 is among those who hold that all experimental and clinical hypertension is of renal origin. When the adrenal glands are removed from an animal with renal hypertension, the blood pressure falls. When the animal is treated with adrenal cortical extracts or with steroids, the hypertension reappears. Hereby, the experimenter can establish a situation in which the primary cause of hypertension is clearly referable to the kidney, and yet the hormones of the adrenal cortex must be present in order to support the overt manifestation of the disease.

Diabetes: We know with certainty the primary cause of diabetes which follows pancreatectomy in experimental animals. It is insulin lack. And yet, when the glucocorticoids are withdrawn by adrenalectomy, the diabetes is ameliorated. The glycosuria can be re-established at its preadrenalectomy level by treatment with normalizing doses of adrenal cortical extract or one of the glucocorticoids. The role of the adrenal cortical hormones in this situation can best be explained as secondary or permissive or supporting.

Will exposure of mildly diabetic animals to nonspecific stress-known to cause an increased secretion of corticoids-cause exacerbation of the diabetes? Although there are a few diabetogenic agents which could be described as stressful, nonspecific forms of stress fail to worsen diabetes. To the contrary, there is a growing body of information about stressors causing some suppression of glycosuria under rigidly controlled experimental conditions.