Pathogenesis of the Cardiovascular and Renal Changes Which Usually Accompany Malignant Hypertension

Abstract

Expts. on 48 albino rats revealed that constriction of the aorta by means of a ligature between the origins of the 2 renal arteries may be gauged so as to completely inhibit, urine formation in the kidney whose artery originates caudad to the ligature. The tubular epithelia of such kidneys show no signs of degeneration or necrosis, although the nephronic lumina disappear and the organ assumes the appearance of an endocrine gland. Such "endocrine kidneys" continue to elaborate humoral substances which elicit the changes characteristic of hypertensive disease in the remaining cardiovascular system. This shows that the formation of urine by a kidney is not a necessary prerequisite for its endocrine activity. The compensatory hypertrophy normally elicited by unilateral nephrectomy is inhibited by the presence of a purely "endocrine kidney" on the other side. Hence the growth of renal tissue must be regulated by renal humoral agents. Although the "endocrine kidney" is much below normal size, it is still responsive to the renotrophic effect of pituitary extracts. Under their influence, numerous mitotic divisions appear in the tubular epithelia and the wt. of the organ increases. Partial constriction of the renal artery completely protects the kidney against nephrosclerosis. This protection is effective against humoral substances formed by this kidney, although they are elaborated in sufficient quantities to produce nephrosclerosis in the contralateral kidney. The protection is also effective against the nephrosclerosis produced by anterior pituitary prepns. as shown by the fact that treatment with such substances produces nephrosclerosis only in the normal and not in the "endocrine kidney". From this it is concluded that increased intra-vascular pressure is essential for the production of nephrosclerosis, since the humoral substances (renal and hypophyseal), sufficient to produce lesions in the normal kidney, do not cause nephrosclerosis in the "clamped" kidney of the same animal. Periarteritis nodosa and a special type of myocarditis (similar to that seen in acute rheumatic fever) can be produced by adrenal hypophyseal and by renal hormones. Like nephrosclerosis, these lesions are apparently the result and not the cause of the exptl. renal hypertension. In the late stages of exptl. nephrosclerosis, the contraction of the renal arterioles may further increase renin production and thus cause a vicious circle, as a result of which the blood pressure is increasingly augmented until death ensues.