The NADPH oxidase inhibitors iodonium diphenyl and cadmium sulphate inhibit hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries

Interest surrounds the role of an NADPH oxidase-like enzyme in hypoxic pulm onary vasoconstriction (HPV). We have studied the effects of the NADPH oxid ase inhibitors iodonium diphenyl (ID) and cadmium sulphate (CdSO4) upon HPV of isolated rat pulmonary arteries (n = 73, internal diameter 545+/-23 mum ). Vessels were preconstricted with prostaglandin F-2 alpha (PGF(2 alpha), 0.5 or 5 muM) prior to a hypoxic challenge, 1D (10 or 50 muM), CdSO4 (100 m uM) or vehicle (50 mul) was added for 30 min before re-exposure to PGF(2 al pha) and hypoxia, ID and CdSO4 significantly inhibited HPV, In vessels prec onstricted with 5 muM PGF(2 alpha) ID (10 and 50 muM) reduced HPV from 37.4 +/-5.6 % to 9.67+/-4.4% of the contractile response elicited by 80 mM KCI ( P<0.05) and from 30.1+/-5.0% to 0.63+/-0.6% 80 mM KCI response (P<0.01), re spectively. CdSO4 (100 muM) reduced HPV from 29.4+/-4.0% to 17.1+/-2.2% 80 mM KCI response (P<0.05). In vessels preconstricted with 0.5 <mu>M PGF(2 al pha), ID (10 and 50 muM) reduced HPV from 16.0+/-3.15% to 3.36+/-1.44% 80 m M KCI response (P<0.01) and from 15.0+/-1.67% to 2.82+/-1.40% 80 mM KCI res ponse (P<0.001), respectively. Constriction to PGF(2 alpha) was potentiated by ID. ID and CdSO4, at concentrations previously shown to inhibit neutrop hil NADPH oxidase, attenuate HPV in isolated rat pulmonary arteries. This s uggests that an NADPH oxidase-like enzyme is involved in HPV and could act as the pulmonary oxygen sensor.