Toyohisa Eguchi

Mechanism of age-related changes in renin and adrenocortical steroids

Age‐related changes in plasma renin activity (PRA) and in plasma levels of adrenocortical steroids were studied in 140 normotensive men and 128 normotensive women. All were free of disease, and their ages ranged from 20 to 86 years. PRA decreased gradually with age in both men and women, and was slightly lower in women than in men. In the older subjects, the responses of PRA to the administration of furosemide or to dietary sodium restriction plus the upright position for blood sampling were significantly less than in the younger subjects. Apparently the suppression of PRA with age is due either to dysfunction of the juxtaglomerular cells induced by aging, or to reduction in the number of functioning nephrons. The plasma level of aldosterone was also reduced with age, but the levels of desoxycorticosterone, corticosterone, and cortisol were not significantly affected. The suppression of aldosterone seemed to be chiefly dependent upon the suppression of renin activity. However, the possibility remains that disturbed function of the glomerular cells with aging also is related to the suppression of aldosterone, since the response of aldosterone to dietary sodium restriction (upright position for blood sampling), to angiotensin II, and to potassium were greatly reduced.

Renin, Aldosterone and Other Mineralocorticoids in Hyperkalemic Patients with Chronic Renal Failure Showing Mild Azotemia

The role of the renin-angiotensin system in the control of aldosterone and other mineralocorticoids was studied in 9 hyperkalemic patients with chronic renal failure showing mild azotemia (group I) and 6 normokalemic patients with chronic renal failure showing creatinine clearance similar to that in group I (group II). In group I, the plasma renin activity (PRA) was significantly low and plasma aldosterone (PAC) and 18-hydroxycortisterone (18-OH-B) were also significantly reduced. In group II, PRA was normal or slightly increased, and PAC and 18-OH-B were also normal or slightly increased. Both the PAC and 18-OH-B in group I were stimulated by ACTH and angiotensin II, although the responses were less than those in group II. In 2 patients of group I where PRA moved into the normal range after administration of furosemide, the plasma 18-OH-B and PAC also reached the lower limit of normal. These results suggest that suppression of the renin-angiotensin system is probably related to functional disturbance in the conversion from B to 18-OH-B and/or 18-OH-B to aldosterone in most abnormally hyperkalemic patients with chronic renal failure.

Effect of Angiotensin I Converting Enzyme Inhibitor, SQ 14225, on Renin Production and Release

Renin production and release induced by angiotensin I converting enzyme inhibitor (CEI), SQ 14225, were studied in male Wistar rats. Acute studies on the effects of CEI (4.6 mumol/kg, i.m. every 6 h for 48 H) in rats revealed a significant reduction in angiotensin II levels and a marked increase in plasma renin activity (PRA). There were no appreciable changes in renal content (RRC) and the juxtaglomerular cell granulation index (JGI). In rats which had received CEI in their drinking water (0.92 mumol/ml) for 12 days, angiotensin II levels were decreased markedly and urinary excretion of sodium was increased, but the reduction in blood pressure was slight. PRA, JGI and RRC were markedly increased in these animals. The kidneys of CEI-treated rats exhibited conspicuous vascular dilatation. CEI treatment of sodium-depleted rats resulted in a reduction of the increased JGI and RRC and in a further increase in PRA. Our findings suggest that CEI administration may initially effect stimulation of renin release from the juxtaglomerular apparatus and that prolonged CEI administration results in a gradual stimulation of renin production.

Studies on the Mechanism of Secretion of Adrenal Steroid Hormones from Adenomas of Primary Aldosteronism and Cushing's Syndrome

The mechanism of secretion of adrenal steroid hormones from adenomas of primary aldosteronism and Cushings syndrome was studied in 10 patients with primary aldosteronism and in 3 patients with Cushings syndrome in in vivo and in vitro experiments. In all of the 10 patients with primary aldosteronism, ACTH stimulated aldosterone secretion from the adenomas more significantly than did angiotensin II and III. DOC and cortisol which were contained in the adenomas were also stimulated more significantly by ACTH than by angiotensin II and III. Responses of the adenomas of Cushings syndrome to various stimulations were less than those of primary aldosteronism. Secretion of cortisol and aldosterone from the adenomas of Cushings syndrome was stimulated by ACTH and angiotensin II to a similar degree. From these studies, it seems that secretion of adrenal steroid hormones from adenomas of primary aldosteronism is more sensitive to extradrenal stimulations than that of Cushings syndrome, and ACTH is the main factor in the control of the secretion of adrenal steroid hormones from the adenomas.

Studies on Angiotensin II Receptors in the Adrenal Glands and in the Aorta

The angiotensin II receptor in the rabbit, rat and human adrenal gland and that in the rabbit and rat aorta were studied by using [3H]-angiotensin II ([3H]-AII). The adrenal glands and the aorta of each species were centrifuged at 20,000Xg for 30 min, and pellets which contained 95% of binding sites were collected and diluted by a buffer [20 mM Tris-HCl buffer (pH 7.4), 120 mM NaCl, 0.2% BSA, 1 mM EDTA] and used as a membrane fraction. The binding study was done by incubating the membrane fraction and [3H]-AII. After incubation at 25 degrees C for 30 min, the binding of the membrane fraction and [3H]-AII reached the equilibrium state, and free and bound angiotensin II were separated by 0.48 micrometer filters. Protein concentration was determined according to the method of Lowry. The binding sites fulfilled the criteria of the receptor which has organ and structure specificities, high affinity and reversibility. We could thus measure angiotensin II receptor in this study correctly and concisely. The properties of the angiotensin II receptor were analysed by Scatchard plot. The number of rabbit adrenal receptors (12833 +/- 2115 x 10(-15) mol/mg.protein) (M ++/- SD) was greater than that of the rat (1780 +/- 166 x 10(-15) mol/mg.protein) and that of the human (356 +/- 124 x 10(-15) mol/mg.protein). But the dissociation constant of all species was the same. The number of aorta binding sites was less than that of the adrenal in rabbits and rats. But the dissociation constant of rabbits and rats aorta binding sites was quite similar to that of adrenal glands.