Norman G. Levinsky*,     *Department of Medicine, Boston University School of Medicine, and Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts

Publisher Summary

This chapter provides an overview of natriuretic hormones. Extracellular expansion decreases renal vascular resistance because of changes in blood viscosity, release of vasodilators, or decrease in adrenergic tone to the kidney. The decrease in renal vascular resistance leads to increased peritubular hydrostatic pressure. The decrease in filtration fraction and hemodilution, if saline is infused, lowers peritubular protein concentration and oncotic pressure. These changes in peritubular physical factors inhibit proximal tubular sodium re-absorption. This inhibition, combined with an increase in filtered sodium, causes a marked increment in the delivery of sodium to the loop of Henle and beyond. If hyperoncotic albumin is the infusate or in certain sodium-retaining states, nearly the entire extra load is reabsorbed distally and any increase in urinary sodium excretion is minimal. Among the factors that might limit distal sodium re-absorption during saline loading are an increase in blood flow and a decrease in peritubular oncotic pressure in the medulla. Many of the nonhormonal factors can be measured only with difficulty or not at all. There is some direct evidence for disproportionate increases in filtration in superficial nephrons during acute and chronic volume expansion. However, there is opposing evidence about redistribution, both of plasma flow and of filtrate. Recent work indicates that changes in plasma sodium concentration alter tubular re-absorption of sodium directly. Hypernatremia causes natriuresis that is in part independent of increased filtered sodium load and extracellular volume expansion.

I Introduction

During the past decade, there has been a great burst of effort in many laboratories to isolate and identify a natriuretic hormone. There had been speculation about such a hormone for many years previously (Smith, 1957), and sporadic attempts had been made to find it. With the appearance of the work by de Wardener and associates in 1961, attention was focused on factors other than filtered sodium and aldosterone as determinants of sodium excretion. This work was quickly confirmed by several groups (Levinsky and Lalone, 1963; Rector et al., 1964) and the rush to find the natriuretic hormone was on.

The key observations of de Wardener’s group were relatively simple. Dogs given supramaximal amounts of mineralocorticoids were infused with saline. In a number of dogs, sodium excretion increased despite spontaneous falls in the glomerular filtration rate. In two additional dogs, sodium excretion increased during saline expansion despite deliberate reduction of glomerular filtration by partial occlusion of the aorta above the renal arteries. These observations indicated that some factor other than increased filtered sodium or decreased aldosterone was involved in the natriuretic response to acute volume expansion. There had been numerous suggestions previously that variations in sodium excretion could occur independently of changes in filtered sodium. Careful review of this work (Wesson, 1957) had led to continued skepticism about the need for other explanations, since large increases in sodium excretion were mathematically equivalent to small, possibly undetectable, percentage increases in filtered sodium. However, the demonstration by de Wardener et al. (1961) and confirmation by others that sodium excretion could increase in dogs receiving mineralocorticoid hormones despite definite reduction of filtered sodium forced even the most skeptical to concede the existence of a “third factor” in the regulation of sodium excretion by the kidney.

While recent work has established beyond doubt that at least one factor other than aldosterone and filtered sodium load is involved, evidence for the thesis that a natriuretic hormone is secreted in response to volume expansion is by no means definitive. The purpose of this review is to evaluate this evidence. Since work in this area continues at a rapid pace, it is important to note that this is being written in May 1973.

II An Outline of Current Concepts of the Regulation of Renal Sodium Excretion