Modulatory effects of endothelin on baroreflex activation in the nucleus of the solitary tract

• Published in: European journal of pharmacology Vol. 351; no. 2; pp. 203 - 207
• Main Authors: Mosqueda-Garcia, Rogelio, Appalsamy, Martin, Fernandez-Violante, Roxana, Hamakubo, Takao
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 19.06.1998; Elsevier
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Baroreflex - drug effects; Baroreflex - physiology; Biological and medical sciences; Blood and lymphatic vessels; Brainstem; Cardiology. Vascular system; Cardiovascular function; Endothelin Receptor Antagonists; Endothelins - physiology; Experimental diseases; Hypertension; Male; Medical sciences; Microinjection; Microinjections; Oligopeptides - pharmacology; Peptides, Cyclic - pharmacology; Piperidines - pharmacology; Rat; Rats; Rats, Sprague-Dawley; Receptors, Endothelin - physiology; Solitary Nucleus - drug effects; Solitary Nucleus - physiology; Hypertension; Microinjection; Rat; Cardiovascular function; Brainstem; Endothelin; Peptide hormone; Rodentia; Solitary nucleus; Vertebrata; Mammalia; Animal; Baroreflex; Intracerebral administration; Vasoconstrictor agent; Antagonist; Hemodynamics; Biological receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00365-3

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 ET A 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 ET B receptor antagonist N- cis-2,6-dimethylpiperidinocarbonyl- l- γ-MeLeu- d-Trp(COOCH 3)- 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 ET A receptor antagonist, except that the hypertensive and hypotensive responses were more pronounced while the baroreflex slope was similarly increased. In contrast, the endothelin ET B 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 ET A receptor subtype.