Endogenous endothelin attenuates the pressor response to acute environmental stress via the ETA receptor.
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 ET(A) 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 ET(B) receptor-deficient (ET(B) sl/sl) rats fed normal salt (NS; 0.8% NaCl), high salt (HS; 8% NaCl), and HS plus the ET(A) receptor antagonist ABT-627 (5 mg.kg(-1).day(-1)) on successive weeks. MAP was chronically monitored by telemetry. Total pressor response (area under the curve) was significantly reduced in ET(B) sl/sl rats maintained on a HS vs. NS diet [-6.8 mmHg (SD 18.7) vs. 29.3 mmHg (SD 8.1) x 3 min, P < 0.05]. Conversely, the total pressor response was augmented in both wild-type [34.2 mmHg (SD 29.2) x 3 min, P < 0.05 vs. NS] and ET(B) sl/sl rats [49.1 mmHg (SD 11.8) x 3 min, P < 0.05 vs. NS] by ABT-627. Blockade of ET(B) receptors in Sprague-Dawley rats caused an increase in basal MAP that was enhanced by HS and lowered by mixed ET(A)/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 ET(A) 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.
D'Angelo
Gerard
G
Vascular Biology Center and Department of Physiology, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912-2500, USA. gdangelo@mail.mcg.edu
Pollock
Jennifer S
JS
Pollock
David M
DM
D000208:Acute Disease; D000392:Air Movements; D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000502:physiology
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017673:Sodium Chloride, Dietary