Although many studies have shown that acute alkalosis causes a decrease in hypoxic pulmonary vasoconstriction; others have shown that alkalosis may enhance vascular smooth muscle contractility. Our previous work suggests that the net response to alkalosis reflects a balance between increased modulation of vasomotor tone and enhanced contractility. In this study, we further examined effects of alkalosis on vasoconstriction by measuring responses to hypoxia (4% O2) and the thromboxane mimetic, U46619 (0.1 μg/kg.min), following 90 minutes of normoxic alkalosis (CO2 = 3%, pH ≈ 7.52) or normocarbia (CO2 = 5%, pH ≈ 7.35) in blood-perfused lungs of 1 month old lambs. Pulmonary artery pressures (Ppa in mmHg) were determined at constant flow during normoxia and following each pressor stimulus. Data are expressed as mean Ppa ± SEM and were compared by two way ANOVA (* = p<0.05). Normoxic and hypoxic Ppa were the same under both conditions, however the response to U46619 was greater in alkalotic lungs. These data suggest that not only did alkalosis fail to modulate hypoxic pulmonary vasoconstriction when hypoxia followed induction of normoxic alkalosis, but thromboxane-induced vasoconstriction was enhanced. Further studies are needed to elucidate why the response to hypoxia and U46619 infusion differed following 90 minutes of alkalosis. Nonetheless, the enhanced pressor response to U46619 in this study suggests that alkalosis therapy may have undesired effects in patients with pulmonary hypertension. Supported by the Department of Pediatrics at the University of Maryland. Table

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