Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs.
A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.
Takeoka
M
M
Research Centre for Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan.
Ishizaki
T
T
Sakai
A
A
Chang
S W
SW
Shigemori
K
K
Higashi
T
T
Ueda
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000502:physiology*; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)