Contribution of endothelin to pulmonary vascular tone under normoxic and hypoxic conditions.
The contribution of endothelin to resting pulmonary vascular tone and hypoxic pulmonary vasoconstriction in humans is unknown. We studied the hemodynamic effects of BQ-123, an endothelin type A receptor antagonist, on healthy volunteers exposed to normoxia and hypoxia. Hemodynamics were measured at room air and after 15 min of exposure to hypoxia (arterial PO(2) 99.8 +/- 1.8 and 49.4 +/- 0.4 mmHg, respectively). Measurements were then repeated in the presence of BQ-123. BQ-123 decreased pulmonary vascular resistance (PVR) 26% and systemic vascular resistance (SVR) 21%, whereas it increased cardiac output (CO) 22% (all P < 0.05). Hypoxia raised CO 28% and PVR 95%, whereas it reduced SVR 23% (all P < 0.01). During BQ-123 infusion, hypoxia increased CO 29% and PVR 97% and decreased SVR 22% (all P < 0.01). The pulmonary vasoconstrictive response to hypoxia was similar in the absence and presence of BQ-123 [P = not significant (NS)]. In vehicle-treated control subjects, hypoxic pulmonary vasoconstriction did not change with repeated exposure to hypoxia (P = NS). Endothelin contributes to basal pulmonary and systemic vascular tone during normoxia, but does not mediate the additional pulmonary vasoconstriction induced by acute hypoxia.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Wendy
W
Johnson
Anju
A
Nohria
Leslie
L
Garrett
James C
JC
Fang
James
J
Igo
Miyuki
M
Katai
Peter
P
Ganz
Mark A
MA
Creager
D000208:Acute Disease; D000328:Adult; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011652:Pulmonary Circulation; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D012008:Recurrence; D012016:Reference Values; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000503:physiopathology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)