Urinary adrenomedullin is related to ET-1 and salt intake in patients withmild essential hypertension

Adrenomedullin (ADM) infusion increases salt excretion in the rat. However. there is no evidence that this substance is related to changes in salt int ake in humans. In this study we sought whether the urinary excretion rate o f this autacoid is related to salt intake and by the expected changes in ar terial pressure in patients with mild essential hypertension. The influence of salt intake on the renal excretion of ADM was investigated in 55 hypertensive patients in a double blind. randomized and crossover st udy comparing a 2-week 50 mmol/day salt intake period with a 150 mmol/day s alt intake period. Twenty-four-hour ADM and endothelin-l (ET-1) excretion r ate were measured by radioimmunoassay on preextracted urinary samples (intr aassay confidence variable <8%). The antibodies used in these assays had mi nimal ADM-ET-1 cross-reactivity (<1%). Twenty-four-hour microalbuminuria wa s measured by nephelometry. On univariate analysis changes in urinary ADM were significantly related to those in salt excretion (r = 0.33, P = .01)as well as to changes in urinar y ET-1 (r = 0.56, P = .0001). Furthermore, changes in urinary albumin excre tion were related to those in urinary ET-1 (r = 0.26, P = .05), but were in dependent of those in urinary ADM (P = .19). In a multiple regression model including age, sex, body mass index, and changes in systolic pressure, pla sma renin activity and plasma aldosterone and urine volume, salt excretion resulted as the stronger independent predictor of urinary ADM (r = 0.33, P = .01). However, changes in urinary salt lost prediction power (P = .11) fo r urinary ADM when urinary ET-1 was introduced into the model. In this mode l (multiple r = 0.31) urinary ET-1 resulted to be the only independent pred ictor of urinary ADM (beta = 0.56, P = .0001). This study is the first to show that the renal excretion of ADM is related to changes in salt intake and that it is tightly linked to that of ET-1. Th e data support the notion that these autacoids play a role in the regulatio n of sodium metabolism in patients with mild hypertension. The intercorrela tions between ET-1, ADM, and microalbuminuria are compatible with the hypot hesis that ET-1 is involved in a salt-induced increase in glomerular pressu re and suggest that ADM may act as a counterregulatory factor in this situa tion. (C) 2001 American Journal of Hypertension, Ltd.