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 baroreflex activation. After control baroreflex slopes were obtained, the animals received bilateral intra-nucleus tractus solitarii microinjections of saline, or equimolar doses (4 pmol/60 nl) of the endothelin ETA receptor antagonist cyclo (D-Trp-D-Asp-Pro-Val-Leu (BQ-123), Homopiperinidinyl-CO-Leu-D-Trp(CHO)-D-Trp-OH (BQ-610), or the endothelin ETB receptor antagonist N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-MeLeu-D-Trp( COOCH3)-D-Nle (BQ-788). Intra-nucleus tractus solitarii administration of BQ-123 resulted in a brief initial pressor effect followed by hypotension which 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 endothelin ETA receptor antagonist, except that the hypertensive and hypotensive responses were more pronounced while the baroreflex slope was similarly increased. In contrast, the endothelin ETB receptor antagonist did not evoke appreciable changes in hemodynamics or in baroreflex slopes. Our results support the concept that endothelin prominently affects reflex cardiovascular function through the endothelin ETA receptor subtype.
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2195, USA. rogelio.mosqueda@mcmail.vanderbilt.edu
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Mosqueda-Garcia
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Appalsamy
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Fernandez-Violante
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Hamakubo
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; C087220:BQ 610; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)