Hypoxia enhances agonist-induced pulmonary arterial contraction by increasing calcium sequestration

Abstract

The effects of hypoxia on norepinephrine-induced contraction to explain why rabbit pulmonary arteries must be precontracted to observe a hypoxic response were studied. A force transducer was used to record the tone of isolated rabbit intrapulmonary artery rings placed in an organ chamber perfused with a physiological solution at 37 degrees C. Norepinephrine (10(-7) M) induced a phasic followed by a tonic contraction, and hypoxia increased the former and decreased the latter. Removal of external calcium (zero calcium solution) abolished the tonic contraction but left the phasic contraction intact. In the zero calcium solution, hypoxia increased the amplitude of the phasic contraction (9.8 +/- 7.4 vs. 13.3 +/- 11.9 mN) and decreased the 50% relaxation time (59 +/- 38 vs. 48 +/- 22 s). Hypoxia also increased the caffeine (5 mM)-induced contraction. This hypoxic increase in amplitude was abolished by ryanodine (100 microM). The hypoxic decrease in the 50% relaxation time was reduced by cyclopiazonic acid (1-10 microM). Therefore, hypoxia increases the reuptake of calcium by calcium pumps sensitive to cyclopiazonic acid in the caffeine- and ryanodine-sensitive stores.