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

Abstract

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 (PO2 11-15 mm Hg) without prior stimulation with an agonist. These contractions are readily reversible by readministration of oxygen. 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. 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. Furthermore, addition of H2O2 (10(-5) M-3 x 10(-4) M) caused concentration-dependent relaxation of the hypoxic contraction while larger concentrations (10(-3) M and 3 x 10(-3) M) caused contraction that did not respond to readministration of oxygen. 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 H2O2 by superoxide dismutase maintains the relaxed state during normoxia.