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 × 10-5 M) and angiotensin-II-induced pulmonary vasoconstriction (IC50=5.0 × 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 hypoxiaor 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. © 1990 Springer-Verlag.