THE PRODUCTION OF HYPERTENSION, NEPHROSCLEROSIS AND CARDIAC LESIONS BY METHYLANDROSTENEDIOL TREATMENT IN THE RAT¹

Abstract

Earlier investigations had shown that chronic overdosage with mineralo-corticoids, such as desoxycorticosterone acetate (DCA), can produce a syndrome of “hyalinosis.” Its manifestations differ somewhat in various species. In the rat, the animal most commonly used for this kind of study, hyalinosis is characterized by nephrosclerosis (glomerular and arteriolar hyalinization, hyalin casts), a “rheumatic-like” myocarditis (partially hyalinized granulomatous nodules in the heart) and periarteritis nodosa (with hyalinization and inflammation, especially in the mesenteric and cerebral vessels). These morphologic changes are accompanied by hypertension and polyuria. Although, with prolonged and heavy DCA overdosage, this syndrome can be elicited even in the intact rat on a normal diet, its development is greatly accelerated by the “conditioning” effect of unilateral nephrectomy and a high NaCl intake. The hypothesis has been advanced that excess production of, or unusual sensitization to, endogenous mineralo-corticoids may be an important factor in the pathogenesis of comparable disease manifestations in man (Selye, 1950, 1952).