POTENTIATION OF THE HYPOXIC CONTRACTION OF GUINEA-PIG ISOLATED PULMONARY-ARTERIES BY 2 INHIBITORS OF SUPEROXIDE-DISMUTASE

1. Isolated proximal and distal extralobar branches of the pulmonary a rtery of the guinea-pig develop slow and well-sustained contractions i n response to hypoxia (P-O2 11-15 mm Hg) without prior stimulation wit h an agonist. These contractions are readily reversible by readministr ation of oxygen. 2. Incubation of these preparations with diethyldithi ocarbamic acid (DETCA, 5 mM for 30 min), an inhibitor of superoxide di smutase, significantly increased the hypoxic contractions whether DETC A was added before the challenge with hypoxia or after the hypoxic con traction had reached a plateau. This treatment also reduced the oxygen -induced relaxation. 3. Similarly, incubation with triethylenetetramin e (TETA, 5 mM for 30 min), another inhibitor of superoxide dismutase, produced larger potentiation of the hypoxic contraction in the two pre parations and reduced the oxygen-induced relaxation. 4. Furthermore, a ddition 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 re administration of oxygen. 5. These observations suggest that during hy poxic stress, the accumulation of superoxide anions may participate in the hypoxia-induced contraction and that the metabolism of these radi cals into H2O2 by superoxide dismutase maintains the relaxed state dur ing normoxia.