DIVERGENT RESPONSES OF ARTERIOSCLEROTIC AND NON-ARTERIOSCLEROTIC RATS TO A CATABOLIC DOSE OF CORTISONE

Abstract

ABSTRACT Male and female rats bred repeatedly develop arteriosclerosis spontaneously. Current information indicates that stimulation of the hypothalamic-pituitary-adrenal axis in association with the active, repeated breeding may be responsible for the increased adrenocortical steroid production which would account for the abnormal lipid, carbohydrate and protein metabolism and arteriosclerosis observed in these animals. Arteriosclerotic breeder rats and non-arteriosclerotic virgin rats were given chronic injections of cortisone. The arteriosclerotic animals showed the most significant catabolic effects due to overdose with steroid, i. e., loss in body weight, disuse atrophy of the adrenal gland, reduced serum corticosterone levels, thymus gland involution, myocardial and renal changes. The excess glucocorticoid caused an acceleration of the usual pattern of development of the arterial disease and increased severity of the pre-existing arteriosclerosis. The excess endogenous steroid did not induce arterial damage in previously non-arteriosclerotic animals. It is believed that the increased activity of the hypothalamic-pituitary-adrenal axis in repeatedly bred rats conditions the arterial wall towards derangement of connective tissue ground substance and elements and the development of arteriosclerosis, i. e., a hormonal basis for the pathogenesis of this model of cardiovascular disease.