Effect of cyclic guanosine monophosphate on hypoxic and angiotensin-II-induced pulmonary vasoconstriction.
We examined, in isolated blood perfused rat lungs, the effect of the cell permeable 8-bromo derivative of cGMP on pulmonary vasoconstriction induced by either alveolar hypoxia or angiotensin II. 8-Bromo cGMP dose-dependently reduced both hypoxia-(IC50 = 2.2 X 10(-5) M) and angiotensin-II-induced pulmonary vasoconstriction (IC50 = 5.0 X 10(-5) M). This effect of 8-bromo cGMP on pulmonary vasoconstriction was not affected by cyclooxygenase blockade. M & B 22948 (0.1 mM), an inhibitor of cGMP-phosphodiesterase, reduced synergistically with 8-bromo cGMP the hypoxia or angiotensin-II-induced vasoconstriction. The cGMP-phosphodiesterase inhibitor M & B 22948, by itself, selectively reduced hypoxia-induced vasoconstriction, suggesting a modulating effect of endogenous cGMP during hypoxic vasoconstriction.
Fujimoto
K
K
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Sakai
A
A
Yoshikawa
S
S
Shinozaki
S
S
Matsuzawa
Y
Y
Kubo
K
K
Kobayashi
T
T
Ueda
G
G
Sekiguchi
M
M
Voelkel
N F
NF
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000187:drug effects*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
D011688:Purinones; D000804:Angiotensin II; C016276:8-bromocyclic GMP; D008469:Meclofenamic Acid; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP