The hemodynamic effects of endothelin receptor antagonism during a venous air infusion in dogs.
Endothelin (ET) is involved in the humoral component of the vasoconstriction during pulmonary embolism. We examined the effects of selective ET receptor antagonists on the hemodynamic and respiratory changes and on serum thromboxane B2 (TXB2) levels, during a continuous venous air infusion (VAI) in anesthetized mongrel dogs. The VAI (0.2 mL x kg(-1) x min(-1)) was initiated 5 min after an injection of saline (controls, n = 7), 1 micromol of the selective ET(A) receptor antagonist JKC-301 (group A, n = 6), or 1 micromol of the selective ET(B) receptor antagonist BQ-788 (group B, n = 6). Hemodynamic evaluation was performed every 15 min of VAI, and blood samples were drawn for blood gas analysis and TXB2 determinations. The increase in pulmonary perfusion pressure after 30 min of VAI was attenuated in Group A compared with the controls and Group B (Group A = 7+/-1 mm Hg; Group B = 16+/-1 mm Hg; controls = 14+/-1 mm Hg; P < 0.05). Pulmonary vascular resistance showed a similar behavior. TXB2 concentrations increased after 60 min of VAI in the controls and in Group B, but not in Group A (controls = 48%; Group B = 104%; Group A = 18%; P < 0.05 for controls and Group B). Similar decreases in Pao2 and Sao2 were observed in the three groups. We conclude that antagonism of ET(A) receptors attenuates the hemodynamic changes and blunts the increase in thromboxane A2 production during a VAI in dogs.


CONCLUSIONS
We evaluated the effects of endothelin receptor antagonists during a venous air infusion in dogs. EndothelinA receptor antagonism attenuated the hemodynamic changes and blunted the increase in thromboxane A2 production in this setting.
Tanus-Santos
J E
JE
Department of Pharmacology, State University of Campinas, São Paulo, Brazil. tanus@unicamp.br
Gordo
W M
WM
Udelsmann
A
A
Moreno
H
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004285:Dogs; D004618:Embolism, Air / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D015656:Respiratory Mechanics / Q000502:physiology; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; C096173:JKC 301; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; D013929:Thromboxane B2; D013928:Thromboxane A2