MODULATORY EFFECTS OF ENDOTHELIN ON BAROREFLEX ACTIVATION IN THE NUCLEUS OF THE SOLITARY TRACT

In this study, we determine the effects of endogenous endothelin on ba roreflex activation. After control baroreflex slopes were obtained, th e animals received bilateral intra-nucleus tractus solitarii microinje ctions of saline, or equimolar doses (4 pmol/60 nl) of the endothelin ETA receptor antagonist cycle (D-Trp-D-Asp-Pro-Val-Leu (BQ-123), Homop iperinidinyl-CO-Leu-D-Trp(CHO)-D-Trp-OH (BQ-610), or the endothelin ET B receptor antagonist peridinocarbonyl-L-gamma-MeLeu-D-Trp(COOCH3)-D-N le (BQ-788) Intra-nucleus tractus solitarii administration of BQ-123 r esulted in a brief initial presser effect followed by hypotension whic h resolved by 15 min. The baroreflex slope was significantly enhanced when tested 15 min after BQ-123 treatment (from 2.4 +/- 0.5 ms/mmHg to 3.5 +/- 0.4 ms/mmHg). Similar effects were observed with the other en dothelin ETA receptor antagonist, except that the hypertensive and hyp otensive responses were more pronounced while the baroreflex slope was similarly increased. In contrast, the endothelin ETB receptor antagon ist did not evoke appreciable changes in hemodynamics or in baroreflex slopes. Our results support the concept that endothelin prominently a ffects reflex cardiovascular function through the endothelin ETA recep tor subtype. (C) 1998 Elsevier Science B.V. All rights reserved.