Circadian rhythm of urinary endothelin-1 excretion in mild hypertensive patients☆

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide with diverse physiologic actions and has been considered to be involved in the pathogenesis of hypertension. We sought to investigate the role of renal synthesis of ET-1 in the regulation of daily sodium homeostasis and the possible contribution of renal synthesized ET-1 in the pathogenesis of essential hypertension (EHT). Urinary ET-1-like immunoreactivity (ET-1-L1) was measured by a radioimmunoassay after extraction in 23 EHT patients without detectable target organ damage, and in 11 normotensive controls. All study subjects received a controlled diet during an 8-day study period. Urinary and blood samples were collected by four sampling periods/day from the 4th to 6th days, and on the 7th day, study subjects were given an intravenous infusion of 1250 mL normal saline over 2 h. In the basal state, the urinary sodium and ET-1-L1 excretions showed diurnal patterns in both the normal and hypertensive groups, and urinary ET-1-L1 excretion rate correlated well with urinary sodium excretion rate. There were no differences found in plasma ET-1 levels, urinary ET-1-L1, and sodium excretion rates between the control and hypertensive groups. After saline infusion, ten hypertensive patients showed nonexaggerated natriuresis, and the 24-h urinary ET-1-L1 excretion (47.0+/-4.0 pmol/day), collected during the day of saline infusion, was significantly lower than that of the control group (86.3+/-10.0 pmol/day) or the exaggeratedly natriuretic hypertensive patients (91.7+/-8.4 pmol/ day). Our results suggest that renal ET-1 may be responsible for the renal handling of sodium homeostasis, and alteration of renal ET-1 synthesis may be a contributory factor in the pathogenesis of essential hypertension and salt sensitivity.