Potentiation of the hypoxic contraction of guinea-pig isolated pulmonary arteries by two inhibitors of superoxide dismutase

Abstract

1. 1. Isolated proximal and distal extralobar branches of the pulmonary artery of the guinea-pig develop slow and well-sustained contractions in response to hypoxia (P O2 11–15 mm Hg) without prior stimulation with an agonist. These contractions are readily reversible by readministration of oxygen. 2. 2. Incubation of these preparations with diethyldithiocarbamic acid (DETCA, 5 mM for 30 min), an inhibitor of superoxide dismutase, significantly increased the hypoxic contractions whether DETCA was added before the challenge with hypoxia or after the hypoxic contraction had reached a plateau. This treatment also reduced the oxygen-induced relaxation. 3. 3. Similarly, incubation with triethylenetetramine (TETA, 5 mM for 30 min), another inhibitor of superoxide dismutase, produced larger potentiation of the hypoxic contraction in the two preparations and reduced the oxygen-induced relaxation. 4. 4. Furthermore, addition of H 2O 2 (10 −5 M −3 × 10 −4M) caused concentration-dependent relaxation of the hypoxic contraction while larger concentrations (10 −3M and 3 × 10 −3M) caused contraction that did not respond to readministration of oxygen. 5. 5. These observations suggest that during hypoxic stress, the accumulation of superoxide anions may participate in the hypoxia-induced contraction and that the metabolism of these radicals into H 2O 2 by superoxide dismutase maintains the relaxed state during normoxia.