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The relation between PO2 and vessel tone was studied in isolated porcine left descending coronary artery rings. Porcine left descending coronary artery mounted isometrically and equilibrated in Krebs-bicarbonate solution (37 degrees C, pH 7.4, when gassed with 95% oxygen + 5% carbon dioxide) exhibited spontaneous basal tone. Decreasing bath PO2 to 40%, 20%, and 12% elicited sustained increases in basal tension which were reversible, ranging between 10% and 20% of the contraction induced by 40 mM potassium chloride. Further decreases in PO2 to near zero (anoxia) resulted in relaxation to baseline. Cyclooxygenase inhibitors indomethacin (5.5 X 10(-6) M), aspirin (5 X 10(-5) M), and meclofenamate (10(-5) M) decreased vascular tone and totally prevented coronary vasoconstriction induced by lowering bath PO2 to 12% or 40% but did not affect anoxic vasorelaxation. Neither basal tone nor the vasoconstriction induced by decreases in bath PO2 were influenced by the antihistaminergic drug pyribenzamine (10(5) M) or by the alpha-adrenergic blocker phentolamine (10(-6]. Isoproterenol (10(-9) to 10(-8) M) or an elevation of the bath potassium concentration from 5.9 to 11 mM significantly augmented coronary vasoconstriction induced by lowering bath PO2 from 95% to 40%. Elevation of the bath potassium chloride concentration to 40 mM further increased isometric force but inhibited the vasoconstriction in response to decreasing PO2 from 95% to 40%. Anoxia relaxed contractions induced by 40 mM potassium chloride, histamine, or ouabain. The data suggest the existence of two distinct oxygen-sensitive mechanisms in porcine coronary arteries, both of which regulate vascular tone. One is activated at relative high PO2 values (10-40%), and the vasoconstriction induced by this mechanism is mediated by vascular prostaglandin synthesis. The other is expressed at low PO2 values (near zero), and the depression of mechanical activity by this mechanism may be related to limitation of oxidative energy metabolism. The first mechanism can be augmented by beta-adrenoceptor stimulation indicative of an interaction between vascular prostaglandin synthesis and beta-adrenergic mechanisms in the coronary artery wall.

Two distinct effects of oxygen on vascular tone in isolated porcine coronary arteries.