The NADPH Oxidase Inhibitors Iodonium Diphenyl and Cadmium Sulphate Inhibit Hypoxic Pulmonary Vasoconstriction in Isolated Rat Pulmonary Arteries

R. D. Jones, J. S. Thompson, A. H. Morice

Received March 6, 2000
Accepted June 8, 2000

Summary
Interest surrounds the role of an NADPH oxidase-like enzyme in hypoxic pulmonary vasoconstriction (HPV). We have studied the effects of the NADPH oxidase inhibitors iodonium diphenyl (ID) and cadmium sulphate (CdSO₄) upon HPV of isolated rat pulmonary arteries (n = 73, internal diameter 545± 23 mm). Vessels were preconstricted with prostaglandin F_2a (PGF_2a, 0.5 or 5 mM) prior to a hypoxic challenge. ID (10 or 50 mM), CdSO₄ (100 mM) or vehicle (50 ml) was added for 30 min before re-exposure to PGF_2a and hypoxia. ID and CdSO₄ significantly inhibited HPV. In vessels preconstricted with 5 mM PGF_2a, ID (10 and 50 mM) reduced HPV from 37.4± 5.6 % to 9.67± 4.4 % of the contractile response elicited by 80 mM KCl (P<0.05) and from 30.1± 5.0 % to 0.63± 0.6% 80 mM KCl response (P<0.01), respectively. CdSO₄ (100 mM) reduced HPV from 29.4±4.0 % to 17.1±2.2% 80 mM KCl response (P<0.05). In vessels preconstricted with 0.5 mM PGF_2a, ID (10 and 50 mM) reduced HPV from 16.0± 3.15% to 3.36± 1.44 % 80 mM KCl response (P<0.01) and from 15.0± 1.67 % to 2.82± 1.40 % 80 mM KCl response (P<0.001), respectively. Constriction to PGF_2a was potentiated by ID. ID and CdSO₄, at concentrations previously shown to inhibit neutrophil NADPH oxidase, attenuate HPV in isolated rat pulmonary arteries. This suggests that an NADPH oxidase-like enzyme is involved in HPV and could act as the pulmonary oxygen sensor.

Key words
NADPH oxidase · Hypoxic pulmonary vasoconstriction · Iodonium diphenyl cadmium sulphate · Isolated rat pulmonary artery

Reprint requests
Dr. R. D. Jones, Endocrine and Cardiovascular Research Group, Dept. of Human Metabolism and Clinical Biochemistry, Med. School, University of Sheffield, Beech Hill Road, S10 2RX Sheffield, UK, e-mail: R.D.Jones@sheffield.hull.ac.uk