Modification by severe hypoxia and diltiazem of dog coronary artery contractions in vitro

Abstract

The contractions induced by prostaglandin (PG) F 2α and by Ca 2+ in helical strips of canine coronary arteries exposed to Ca 2+-free medium under severe hypoxia and stimulated by PGF 2α or K + were augmented by the return to normoxia. Inhibition under hypoxia was ranked as follows: Ca 2+-induced contractions in the strips stimulated by PGF 2 α > Ca 2+-induced contractions in the K +-depolarized strips `> PGF 2 α -induced contractions in the Ca 2+ -free medium. The inhibition of arterial contractions during severe hypoxia was not influenced by removal of the endothelium. Treatment with indomethacin attenuated the inhibitory effect of hypoxia on Ca 2+-induced contractions in arteries stimulated by PGF 2α or serotonin but affected neither the Ca 2+-induced contractions in the strips depolarized by excess K + or the PGF 2α-induced contractions in Ca 2+-free medium. Diltiazem attenuated the Ca 2+-induced contactions in arteries stimulated by PGF 2α or K ++ but did not attenuated the PGF 2α-induced contractions in the Ca 2+-free medium during hypoxia or normoxia. Diltiazem also inhibited the contractions caused by re-oxygenation. In conclusion, severe hypoxia inhibited the contractions induced by Ca 2+ in the presence of PGF 2α receptor activation more than those associated with membrane depolarization. The PGF 2α-induced contractions in the Ca 2+-free medium (possibly due to the release of intracellularly stored Ca 2+) may be relatively resistant to severe hypoxia. The hypoxia-induced inhibition of contractions due to Ca 2+ in PGF 2α-stimulated arteries could be associated partly with the release of PGI 2 but not with endothelium-derived relaxing factor(s).