Phyllis M. Hartroft

THE ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN THE CONTROL OF ALDOSTERONE SECRETION

Within the last year, evidence (1-4) has accumulated to show that the kidney secretes a hormone which is a prime regulator of aldosterone secretion. The renal origin of an aldosteronestimulating hormone (ASH) has been demonstrated following acute blood loss (1-3), during chronic thoracic caval constriction (4), and during chronic Na depletion (4). Nephrectomizedhypophysectomized dogs failed to respond to acute hemorrhage with an increase in aldosterone secretion, and acute bilateral nephrectomy of hypophysectomized caval and hypophysectomized Nadepleted dogs resulted in a marked drop in aldosterone secretion. Furthermore, crude saline extracts of kidney produced a striking increase in aldosterone secretion (1-5). In malignant experimental renal hypertension, hyperaldosteronism was consistently present (6). These findings and the reports that renin preparations (6) and synthetic angiotensin II (6-8) increase the rate of aldosterone production suggest the possibility that ASH is renin. The present experiments were undertaken to determine the chemical nature of this ASH by fractionation of crude kidney extracts for aldosterone-stimulating and pressor activity. The renin content of kidneys from dogs with thoracic caval constriction and secondary hyperaldosteronism and from normal dogs has been compared. Since dogs with thoracic caval constriction and Na-depleted dogs do not have hypertension, the response in blood pressure to synthetic angiotensin

Localization of Renin in Juxtaglomerular Cells of Rabbit and Dog Through the Use of the Fluorescent-Antibody Technique

Canine antisera to rabbit and hog renin were coupled to several fluorescein dyes. The antiserum was immunologically adsorbed once each with rabbit-liver and with bone-marrow powder, thereby removing excess dye and eliminating nonspecific staining. Mounted frozen-dried sections of kidneys from sodium- deficient rabbits (in which hyperplasia and hypergranulation of juxtaglomerular [JG] cells were present), from control rabbits, from a sodium-deficient dog, and from sodium-deficient rats were treated with the adsorbed labeled antiserum. Ultraviolet microscopy (direct technique) revealed an intense yel low-green fluorescence sharply limited to the granules of the juxtagloinerular cells in all sections studied from kidneys of rabbit and dog. JG granules in rats did not fluoresce, an observation in accord with the species spe cificity of renin. The indirect (“sandwich”) method was also employed (with adsorbed, labeled, rabbit antiserum to canine globulin), and although slight staining of gloinerular epithelium resulted, that in the JG granules was far more intense. In our hands, the faint glornerular staining was not blocked by prior treatment with unlabeled renin. Staining of JG granules in any kidney paralleled the intensity of JG granulation by light microscopy and the amount of extractable renin in the same kidney. JG-granule staining (direct and indirect techniques) was blocked by neutralization of the antirenin with renin. Heterogenous anti sera (to insulin; to human gamma globulin) failed to stain. Other rabbit tissues (heart, lung, liver) similarly treated with labeled antirenin never stained. If this work can be repeated with immunologically pure renin, the evidence presented here, together with previously published studies from this and other laboratories, will establish beyond any reasonable doubt that the source of renin in the kidney is the juxtaglomerular cell, as postulated first by Goormagh tigh nearly a quarter of a century ago.

Adrenal steroid secretion and a renal-pressor system in the chicken (Gallus domesticus)

Abstract The concentrations of aldosterone and corticosterone in adrenal vein plasma were measured by the double isotope derivative assay in intact cockerels and in cockerels following hypophysectomy, infusion of ACTH, infusion of chicken kidney extracts, or sodium depletion. In sodium-depleted cockerels, renal renin content, index of juxtaglomerular granularity (JGI), and the width of the peripheral zone of the adrenals were also examined. The adrenal vein plasma levels of corticosterone and aldosterone in intact “surgically stressed” cockerels were 6.58 ± 1.47 (SEM) and 0.21 ± 0.06 μg/100 ml, respectively. Infusion of porcine ACTH produced a significant increase in corticosterone but no increase in aldosterone. Concentrations of both steroids were significantly decreased by hypophysectomy while neither sodium depletion nor infusion of chicken kidney extracts produced a detectable change in adrenal veins levels of these steroids. Sodium-depleted cockerels showed a significant increase in JGI. Kidney extracts from sodium-depleted cockerels, when incubated with chicken plasma, produced a significantly greater blood pressure increase in a rat than did kidney extracts from sodium-repleted cockerels. The peripheral zone of adrenals from sodium depleted birds was wider than that of control birds. It is suggested that the pituitary plays a role in maintaining adrenal secretion of aldosterone as well as corticosterone in cockerels. A renal-pressor system was found to be present in the cockerel and could be stimulated by sodium depletion although no steroidogenic action of this system was demonstrable.

Increased Renal Pressor Activity (Renin) in Sodium Deficient Rats and Correlation with Juxtaglomerular Cell Granulation.

Summary Pressor activity (renin) and degree of granulation of juxtaglomerular cells (JGI) of kidneys from normal and sodium-deficient rats were measured. Pressor activity was increased in sodium-deficient animals and correlated (r = 0.80) with degree of granulation of JG cells.