Evidence for endothelin involvement in the response to high salt

Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ETB receptor, may participate;in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk. of baselin e measurements, rats were given either high (10%) or low (0.08%) NaCl in ch ow for the remainder of the experiment (n = 5 in each group). MAP was signi ficantly increased in rats on a high-salt diet (115 +/- 2 mmHg) compared wi th rats on the low-salt diet (103 +/- 2 mmHg; P < 0.05). All rats were then treated with the ETB receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg.kg(-1).day(-1). ETB blockade produ ced an increase in MAP within a few hours of treatment and was significantl y higher in rats on the high-salt diet over a 1-wk period (170 +/- 3 vs. 11 5 +/- 3 mmHg, P < 0.01). To determine whether the increase in MAP during A- 192621 treatment was due to increased ETA receptor activation, all rats wer e then given the ETA-selective antagonist ABT-627 in the drinking water whi le a low-salt/high-salt diet and ETB blockade were continued. ABT-627 decre ased MAP within a few hours in rats on either the high-salt (113 +/- 3 mmHg ) or low-salt (101 +/- 3 mmHg) diet. These results support the hypothesis t hat endothelin, through the ETB receptor, participates in blood pressure re gulation in the response to salt loading.