Pathogenesis of Experimental Arteriosclerosis in the Rat. ∗

Abstract

Summary

1. Pathogenesis of severe arteriosclerosis and disseminated myocardial necrosis, induced in the albino rat by standard renal injury, was investigated. These cardiovascular lesions are due to autointoxication with parathyroid hormone, and this hormone apparently contains an important hypertensive factor. 2. Evidence was presented that excess production of parathyroid hormone, as a consequence of renal dysfunctions, is mediated through the adrenal cortex and that mineralocorticoids are essential for direct or indirect activation of the parathyroid gland. To some degree, androgens can enhance the mineralocorticoid effect, whereas estrogens seem to inhibit emergence of muscular necrosis. The incidence of cardiovascular injury in intact and adrenalectomized rats was found to be substantially higher in male than in female animals. 3. It was shown further that, in the absence of parathyroid glands, mineralocorticoids in excessive dosage fail to produce cardiovascular necrosis, whereas excess parathyroid hormone assures emergence of typical lesions in complete absence of mineralocorticoids. In fact, by providing abundant supplies of parathyroid extract, cardiovascular necrosis was induced without renal injury and even in absence of kidneys. 4. Implications of these findings upon the concept of “metastatic calcification” and upon pathogenesis and therapy of renogenic cardiovascular necrosis and hypertension in human beings are discussed. It is suggested that subtotal parathyroidectomy be tried in preference to adrenalectomy in attempts to arrest rapidly progressive sequellae of malignant hypertension.