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Effect of cyclic guanosine monophosphate on hypoxic and angiotensin-II-induced pulmonary vasoconstriction.

Abstract
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.
AuthorsK Fujimoto, A Sakai, S Yoshikawa, S Shinozaki, Y Matsuzawa, K Kubo, T Kobayashi, G Ueda, M Sekiguchi, N F Voelkel
JournalLung (Lung) Vol. 168 Issue 6 Pg. 333-43 ( 1990) ISSN: 0341-2040 [Print] United States
PMID2177815 (Publication Type: Journal Article)
Chemical References
  • Purinones
  • Angiotensin II
  • 8-bromocyclic GMP
  • Meclofenamic Acid
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • zaprinast
  • Cyclic GMP
Topics
  • 3',5'-Cyclic-GMP Phosphodiesterases (antagonists & inhibitors)
  • Angiotensin II (pharmacology)
  • Animals
  • Cyclic GMP (analogs & derivatives, pharmacology)
  • Dose-Response Relationship, Drug
  • Hypoxia (physiopathology)
  • Lung (drug effects)
  • Male
  • Meclofenamic Acid (pharmacology)
  • Purinones (pharmacology)
  • Rats
  • Vasoconstriction (drug effects)

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