Measurements of plasma renin were made in unilaterally nephrectomized dogs with renal artery stenosis and hypertension. Plasma renin was elevated throughout the course of the malignant renal ...hypertensive disease, and during the first three days only in chronic hypertension. Hypertension was produced by renal artery constriction in unilaterally nephrectomized dogs with prior thoracic caval constriction and in sodium-depleted, left nephrectomized animals. Plasma renin was high in both dogs with caval constriction and sodium depletion before hypertension was added. When the renal artery was constricted, two of the dogs with thoracic caval constriction developed malignant hypertension and a further striking increase in plasma renin occurred. In two other dogs with caval constriction, chronic hypertension developed but plasma renin increased further in only one of the two animals; this occurred during the first four days of hypertension after which plasma renin returned to the high control level. The sodium-depleted dogs developed chronic hypertension following renal artery constriction but no further elevation in plasma renin occurred. Sodium repletion and sodium depletion of chronic hypertensive dogs produced marked changes in plasma renin without alterations in arterial pressure. The present findings revealed a striking correlation between plasma renin and sodium balance but neither bore any relation to the level of arterial pressure.
The primary mechanism leading to hypersecretion of aldosterone during sodium depletion in the dog is increased activity of the renin-angiotensin system. Loss of salt and water leads to renin release ...and increased aldosterone and corticosterone secretion. Plasma renin was elevated within one hour after diuretic administration. The increase in corticosterone production was transient; return of corticosterone to the control level appears to be mediated by the negative corticosteroid feedback mechanism via the anterior pituitary. It is suggested that the role of ACTH in aldosterone production during sodium depletion is a supportive one. In severe sodium depletion decreased plasma sodium and increased plasma potassium concentrations further augment the hypersecretion of aldosterone.
Ethacrynic acid, a potent inhibitor of sodium reabsorption in the ascending limb of Henle's loop, produces a sharp rise in renal venous renin activity within 5 min after intravenous administration in ...anesthetized dogs. This response persists when volume depletion is prevented by returning urinary outflow to the femoral vein. Comparable studies with chlorothiazide, a diuretic with little or no effect on the medullary portion of the ascending limb of the loop of Henle, failed to produce a significant increase in renal venous renin activity.When administered during ureteral occlusion, ethacrynic acid produced no change in renal venous renin activity until ureteral occlusion was released and flow restored. Following release of the ureters, a prompt rise in renal venous renin was again observed within 5 min of release. Control studies of ureteral occlusion yielded a fall in renal venous renin activity following release of the ureter without administration of ethacrynic acid. These studies identify a prompt stimulatory effect of ethacrynic acid on renin release that is unrelated to volume depletion but dependent upon the presence of tubular urine flow. Although further definition of the site and characteristics of the distal tubular mechanism for stimulation of renin release requires more direct study, the data presented here indicate that changes in sodium concentration in distal tubular fluid serve as a stimulus for renin release.
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