ON THE NATURE OF THE INTERDEPENDENCE OF THE ADRENAL CORTEX, NON-SPECIFIC STRESS AND NUTRITION IN THE REGULATION OF NITROGEN METABOLISM*

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Abstract
Acute stress (formalin subcut., severe insulin hypoglycemia, and epinephrine) causes an immediate increase in urea formation in the nephrecto-mized rat but not in the adrenalectomized-nephrectomized rat maintained with saline and DCA. Adrenal cortical extract (ACE) or ACTH, even in massive doses intraven. or intraperit., cause only a delayed increase (3-6 hrs.) in urea formation in the neph-rectomized rat. Following mild stress (small doses of formalin or insulin), no immediate change in N metabolism occurs, but if the animals are treated with adrenal extract an immediate increase in urea formation occurs which is comparable in time of occurrence to that after more severe stresses. Acute or chronic pretreatment with ACE or ACTH does not modify the magnitude of N metabolic response to a dose of formalin which increases urea formation in the untreated nephrectomized rat. Adrenalectomized-nephrectomized rats maintained on cortisone intramusc. and acutely stressed with epinephrine exhibit the same prompt increase in urea formation after stress as do animals with intact adrenals. However, the response in the former is not sustained, presumably because of slow release of cortisone from the crystalline depot. It is concluded in agreement with Ingle that adrenal hormone is necessary but not responsib for the N metabolic response to stress. The concept that adrenal hormone in some way sensitizes the organism to respond to stress with a characteristic metabolic pattern is suggested and discussed. The interdependence of stress, diet and the adrenal cortex in modifying N metabolism is emphasized.