title: Effects of oxygen and glucose deprivation on vasoactivity in isolated bovine middle cerebral arteries.
abstract: The effects of oxygen and glucose deprivation on vasoactivity were investigated using helical strips of bovine middle cerebral artery. Hypoxia, created by reducing the PO2 of the bath, or oxidative inhibition with 2,4 dinitrophenol (DNP) or sodium azide, significantly reduced contractions induced by serotonin. Normal tonic contractions induced with fresh and aged whole blood, or 5-HT became phasic and quickly relaxed to baseline in a hypoxic environment. Glucose elimination from the Krebs medium, or the inhibition of the glycolytic pathway with iodoacetic acid (IAA), did not significantly reduce serotonin-induced contractions. However, contractions were inhibited more with the combination of oxygen and glucose deprivation, or DNP + IAA, than with oxygen deprivation alone. Efforts to produce rigor in this preparation by oxygen/substrate reduction or metabolic inhibition were unsuccessful. Tonic contractions induced by 70 mM potassium became phasic as the Ca++ concentration was reduced. Contractions resulting from the readdition of Ca++ to arteries exposed to calcium-free high potassium solution were significantly reduced in the presence of oxidative and/or glycolytic inhibitors. The uptake of 45Ca++, as measured by the lanthanum technique, decreased as the bath PO2 was reduced in both serotonin stimulated and unstimulated arteries. Glucose deprivation alone did not affect 45Ca++ uptake. This study suggests that hypoxia has a direct inhibitory affect on cerebral vasoactivity mediated by reductions in sarcoplasmic Ca++ uptake.
mesh_terms: D019297:2,4-Dinitrophenol; D000818:Animals; D001386:Azides; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002536:Cerebral Arteries / Q000503:physiopathology*; D004140:Dinitrophenols; D005947:Glucose / Q000502:physiology*; D006019:Glycolysis / Q000187:drug effects; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D007460:Iodoacetamide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010084:Oxidation-Reduction; D011188:Potassium / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D019810:Sodium Azide
chemical_list: D001386:Azides; D004140:Dinitrophenols; D012701:Serotonin; D019810:Sodium Azide; D005947:Glucose; D019297:2,4-Dinitrophenol; D011188:Potassium; D002118:Calcium; D007460:Iodoacetamide