Modification by severe hypoxia and diltiazem of dog coronary artery contractions in vitro.
The contractions induced by prostaglandin (PG) F2 alpha and by Ca2+ in helical strips of canine coronary arteries exposed to Ca2+-free medium under severe hypoxia and stimulated by PGF2 alpha or K+ were augmented by the return to normoxia. Inhibition under hypoxia was ranked as follows: Ca2+-induced contractions in the strips stimulated by PGF2 alpha greater than Ca2+-induced contractions in the K+-depolarized strips greater than PGF2 alpha-induced contractions in the Ca2+-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 Ca2+-induced contractions in arteries stimulated by PGF2 alpha or serotonin but affected neither the Ca2+-induced contractions in the strips depolarized by excess K+ or the PGF2 alpha-induced contractions in Ca2+-free medium. Diltiazem attenuated the Ca2+-induced contractions in arteries stimulated by PGF2 alpha or K+ but did not attenuate the PGF2 alpha-induced contractions in the Ca2+-free medium during hypoxia or normoxia. Diltiazem also inhibited the contractions caused by re-oxygenation. In conclusion, severe hypoxia inhibited the contractions induced by Ca2+ in the presence of PGF2 alpha receptor activation more than those associated with membrane depolarization. The PGF2 alpha-induced contractions in the Ca2+-free medium (possibly due to the release of intracellularly stored Ca2+) may be relatively resistant to severe hypoxia. The hypoxia-induced inhibition of contractions due to Ca2+ in PGF2 alpha-stimulated arteries could be associated partly with the release of PGI2 but not with endothelium-derived relaxing factor(s).
Inoue
S
S
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Kinoshita
M
M
Toda
N
N
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D015237:Dinoprost; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology
D011460:Prostaglandins F; D015237:Dinoprost; D004110:Diltiazem; D011188:Potassium; D010100:Oxygen; D002118:Calcium