REDUCED NATRIURETIC EFFECT OF ATRIAL-NATRIURETIC-PEPTIDE IN NEPHROTIC SYNDROME - A POSSIBLE ROLE OF DECREASED CYCLIC GUANOSINE-MONOPHOSPHATE

To evaluate therapeutic and side effects, atrial natriuretic peptide (ANP) was administered as a pharmacological bolus dose (2 mu g/kg body weight) to 7 patients with nephrotic syndrome and to 13 age- and gender-matched control subjects. The basal glomerular filtration rate was similar, but the blood pressure was slightly higher in the patients than in the controls. Injection of ANP induced a significant increase of sodium excretion in controls (from 0.21 to 0.52 mmol/min, medians, p < 0.01), but not in nephrotics (from 0.21 to 0.32 mmol/min). Urinary output and free water clearance after ANP had been given were also lower in the patients. The natriuretic effect was mediated through inhibition of distal tubular fractional sodium reabsorption, as estimated by the lithium clearance technique, and through an increase of glomerular filtration rate, both effects only significant in the healthy subjects. The blood pressure was reduced to the same extent in the two groups. Although similar levels of ANP were reached in the groups after injection, cyclic guanosine monophosphate (GMP)/ANP was less in the patients, both basally and after ANP injection, and the urinary excretion of cyclic GMP did not increase in the nephrotics (from 478 to 1,220 pmol/min, ns) as in the controls (from 389 to 2,500 pmol/min, p < 0.01). The urinary albumin excretion rate increased significantly in patients, whereas the prostaglandin E(2) excretion increased after ANP administration only in controls. Endothelin, angiotensin II, aldosterone, and arginine vasopressin were unchanged in the two groups. Basal aldosterone was lower and ANP higher in patients than in controls. In conclusion, the natriuretic effect of ANP was reduced in nephrotic patients. This could not be attributed to counterregulatory haemodynamic or hormonal factors, but probably to reduced second messenger cyclic GMP.