Clinical studies have documented an abrupt rise in plasma endothelin-1 (ET-1) coincident with an increase in mean arterial pressure (MAP) during the response to acute stress. We therefore examined the ETA and ET B receptor-dependent effects of ET-1 on the pressor response to acute environmental stress in ET-1-dependent hypertension. Stress was induced by administration of air jet pulses (3 min) in ETB receptor-deficient (ETB sl/sl) rats fed normal salt (NS; 0.8% NaCl), high salt (HS; 8% NaCl), and HS plus the ETA receptor antagonist ABT-627 (5 mg·kg-1·day-1) on successive weeks. MAP was chronically monitored by telemetry. Total presser response (area under the curve) was significantly reduced in ETB sl/sl rats maintained on a HS vs. NS diet [-6.8 mmHg (SD 18.7) vs. 29.3 mmHg (SD 8.1) × 3 min, P < 0.05]. Conversely, the total pressor response was augmented in both wild-type [34.2 mmHg (SD 29.2) × 3 min, P < 0.05 vs. NS] and ETB sl/sl rats [49.1 mmHg (SD 11.8) × 3 min, P < 0.05 vs. NS] by ABT-627. Blockade of ETB receptors in Sprague-Dawley rats caused an increase in basal MAP that was enhanced by HS and lowered by mixed ETA/ET B receptor antagonism; none of these treatments, however, had any effect on the pressor response. These data demonstrate that increasing endogenous ET-1 suppresses the pressor response to acute stress through ETA receptor activation in a genetic model of ET-1-dependent hypertension. These results are consistent with reports that ET-1 can attenuate sympathetically mediated responses. Copyright © 2005 the American Physiological Society.