Time course of pulmonary vasoconstriction with repeated hypoxia and glucose depletion

To examine the effect of hypoxia on pulmonary vascular smooth muscle, rabbit lobar pulmonary artery was suspended in a glucose free solution and both chronologic changes in tension and ATP content were determined together at 30 min intervals after repeated hypoxic challenge (PO2 = 11 +/- 2 mm Hg). The pulmonary artery contracted and its ATP content decreased with hypoxia. This contraction was not inhibited by nifedipine, Ca++ -free EGTA, procaine, phentolamine, isoproterenol, diphenhydramine, prostaglandin E1, atropine or nitroglycerin. Upon reoxygenation (PO2 = 104 +/- 3 mm Hg), the elevated resting tension decreased in a biphasic fashion and the ATP content of the lobar pulmonary artery increased. When hypoxic challenges were repeated, the rate of constriction on hypoxia increased, while the relaxation rate on reoxygenation, tension developed by 30 min of hypoxia and the total amount of ATP decreased. These results suggest that the ATP content in the lobar pulmonary artery is very sensitive to in vitro acute hypoxia and that the Ca++ transport process is more easily impaired by reduction in ATP levels than is the contractile machinery.