The association of a humoral sodium transport inhibitory activity with renal escape from chronic mineralocorticoid administration in the dog.

Abstract

1. Previous studies in dogs given large intravenous saline infusions had shown the presence of an inhibitor of toad bladder sodium transport in jugular venous plasma. In the present study plasma of six dogs on a constant sodium intake was tested for this humoral sodium transport inhibitory (HSTI) activity before and during chronic administration of desoxycorticosterone acetate (DOCA). 2. Renal escape from mineralocorticoid antinatriuresis occurred 2–7 days after beginning treatment with DOCA. No HSTI activity was present in plasma drawn at 9 a.m. during a control period before DOCA administration but it was found in every case on the morning of the day on which escape occurred. A positive correlation was shown between HSTI activity of 9 a.m. plasma and the rate of sodium excretion for the subsequent 24 h period (r = 0·66, P < 0·002). 3. When DOCA administration was continued for several days after escape had occurred in three dogs, oscillations in HSTI activity correlated with oscillations in renal sodium excretion. 4. The degree of antinatriuresis on any given day correlated with the amount of HSTI activity the following morning (r = 0·61, P < 0·0002). This finding suggests that extracellular fluid volume expansion resulting from DOCA-induced antinatriuresis leads to HSTI activity. These results fit the hypothesis that HSTI activity is a natriuretic hormone which plays a role in the mechanism of DOCA escape.