HYPERTENSION AND ADRENOCORTICAL FUNCTION

REPORT II. ADRENOCORTICAL FUNCTION IN EXPERIMENTAL HYPERTENSION

Abstract

It has been shown by Kumar and his associates that infusion of aldosterone (0.5g/48hr, or 1.0g/24hr.) elevates blood pressure in rats. By Gornall (1960), similar increases of blood pressure in responses to aldosterone (0.4-0.5g/100g body weight) were reported in the same animal. It was opposed, however, by Gaint and Gross, who failed to induce experimental hypertension in rats in spite of long-term administration of aldosterone. At that period, numerous attempts were made to elucidate the mechanisms responsible for this experimental hypertension. However, thus far, direct evidence concerning the role of aldosterone in controlling blood pressure remained obscure. But a few groups, such as Gross and his collaborators, led to the same conclusion that, with the very small dosage of aldosterone, there was no increase: in mean arterial pressure, although further progressive rise could be maintained by administration of a large amount of aldosterone (0.2mg/day). Besides, it was demonstrated that the hypertensogenic action of aldosterone in large doses was not so remarkable as that induced by infusion of deoxycorticosterone. On the other hand, persistent hypertension has been produced in animals by constricting the main renal arteries. This experimental hypertension, produced by Goldblatt (1934), reduces the blood flow to the functioning components of the kidneys. The nature of the effective substances responsible for inducing the hypertension has been studied and has subsequently been ascribed primarily to humoral factors from the affected kidneys. But recent observations suggested that the Goldblatt's hypertension might be associated with disturbances of adrenals. From the experiments of several reserchers, such as Page and associates and Freed and collaborators, an adrenal mechanism was involved in the experimental hypertension at least under certain circumstances. For instance, definite elevation of blood pressure due to renal ischemia was, never occured in the bilaterally adrenalectomized animal without substitution treatment. But if these animals had been administered adrenocortical extracts or predonisolone, arterial pressure levels were strikingly elevated in the majority of the animals. The results of these experiments did indicate that adrenocortical function might, in some way, play an important part in initiating some degree of hypertension. Another approach that might offer means of diagnosing functionally significant hypertensive disorders wass the assay of angiotensin in blood, and the attempt by Skeggs to extract the pressor substance was successfully done in horses. The mechanisms controlling the secretion of aldosterone have been incompletely understood, although the immediate stimulus to the adrenal gland was probably angiotension II, at least in certain circumstances. Whatever the possible stimuli for aldosterone secretion might be, the experimental results indicate that renin-angiotensin-aldosterone system seems to play an important role in the maintenance of a certain type of hypertensive disorders. During a study of the effect of adrenal treatment, Skelton (1955) presented a simple technic for the production of the adrenal regeneration hypertension, which could be produced by unilateral adrenalectomy with contralateral adrenal enucleation, unilateral nephrectomy and salt loading. The regenerating adrenal cortices were suggested to be the predominant place of mineral corticoid secretion. Especially, endogenuous aldosterone has been suspected of playing a role in the genesis of hypertension. But the possibility that aldosterone fully sustains hypertension has not been proved yet. As for the adrenal, there have been many morphological researches previously described. However, there appeared to be only fragmentary observations on the adrenocortical function. Therefore, studies about the adrenocortical functions of hypertensive rats have been made and the results have been discussed.