Blunted natriuresis to atrial natriuretic peptide in chronic sodium-retaining disorders

Abstract

Renal responses to atrial natriuretic peptide were examined in conscious dogs with congestive heart failure (tricuspid insufficiency) and in conscious rats with nephrotic syndrome (adriamycin). Heart-failure dogs displayed elevated atrial pressure and heart weights, blunted natriuresis to a saline load, and ascites. Nephrotic rats displayed proteinuria, hypoproteinemia, sodium retention, and ascites. In control animals, atrial natriuretic peptide increased absolute and fractional urine flow rate and urinary sodium excretion. Although atrial natriuretic peptide increased absolute and fractional urine flow rate and urinary sodium excretion in conscious heart-failure dogs and nephrotic rats, the responses were markedly blunted. In heart-failure dogs, infusion of atrial natriuretic peptide increased plasma concentrations of norepinephrine and epinephrine. In nephrotic rats, renal denervation reversed the blunted diuretic and natriuretic responses to atrial natriuretic peptide. Mean arterial pressure, glomerular filtration rate, and p-aminohippurate clearance were affected similarly by atrial natriuretic peptide in heart-failure dogs or nephrotic rats vs. control animals. Conscious congestive heart-failure dogs and conscious nephrotic rats have blunted diuretic and natriuretic responses to atrial natriuretic peptide.

Cellular basis for blunted volume expansion natriuresis in experimental nephrotic syndrome.

“…The results of our experiments suggest that the defect in sodium metabolism in at least one form of experimental nephrosis, that resulting from adriamycin administration, may result from blunted cellular responsiveness to the renal actions of ANP. Other studies have documented that rats treated with adriamycin have a blunted natriuretic response to volume expansion (7) and ANP infusion (19)(20)(21). In recent studies, renal denervation improved both the volume expansion natriuresis (7) and the natriuresis resulting from infusion of ANP IMCD cells .7…”

“…N~ignifi-cantly greater than value e] Nephrotic with vehicle alone, P < 0.05. (19), suggesting that the heightened sympathetic efferent renal nerve activity observed in this model of nephrosis (7) could contribute to abnormal sodium metabolism, and perhaps the ANP resistance which characterizes this and other forms of pathological sodium retention (30). In the present study we sought to investigate the regulation of sodium metabolism in nephrotic syndrome in the context of the resistance to ANP reported by others.…”

“…Recent studies carried out in rats with nephrosis resulting from adriamycin administration have suggested that the ab-normal sodium metabolism accompanying this disorder could reflect impaired responsiveness to circulating ANP (19)(20)(21). This resistance to the natriuretic action of ANP and the blunted natriuresis seen after volume expansion in these rats were shown to improve after renal denervation (7,19).…”

“…This resistance to the natriuretic action of ANP and the blunted natriuresis seen after volume expansion in these rats were shown to improve after renal denervation (7,19). To explore these phenomena further, we have examined the relationship between the natriuretic response to extracellular fluid volume expansion and circulating ANP levels as well as urinary cyclic GMP excretion (an index ofANP bioactivity in the kidneys) in normal and nephrotic rats.…”

Chronic experimental myocardial infarction produces antinatriuresis by a renal nerve-dependent mechanism

“…Sodium retention in heart failure is due to alterations in several volume control mechanisms such as the renin-angiotensin system (1,2), prostaglandins (3,4), natriuretic peptides (2,4,5), vasopressin (6), and the sympathetic nervous system (2,5,7,8). The activation of sodium-retention pathways may be viewed as a compensatory mechanism elic-ited to preserve the hemodynamic balance despite the reduced cardiac output.…”