Pulmonary vascular reactivity to biogenic amines during acute hypoxia

Abstract

The effects of acute hypoxia on the pressor responses to five biogenic amines were studied in isolated blood-perfused cat lungs. Hypoxia (Po2 = 46 +/- 2 Torr) reduced the pressor responses to phenylephrine while changing the pressor responses to epinephrine and norepinephrine to vasodilation. Hypoxia reduced the pressor responses to histamine, and these reductions were preceded by small but significant vasodilations. Hypoxia had no effect on the pressor responses to serotonin. These changes in pulmonary vasoactivity were reversed on reoxygenation, independent of changes in base-line tone and not correlated with circulating catecholamines. We also examined the effects of hypoxia on the pressor responses to norepinephrine during beta-blockade with propranolol and then alpha-blockade with dibenzyline. The vasodilation produced during hypoxia by norepinephrine was blocked by propranolol, and vasoconstriction reappeared. When alpha-blockade was then established, vasodilation to norepinephrine reemerged during hypoxia. These results demonstrate that hypoxia produces changes in pulmonary vascular responsiveness that are acute in nature and reversible. Although the cellular nature of these changes is unknown, the data suggest that hypoxia produces acute shifts in antagonistic adrenergic receptor activity by either 1) reducing alpha- or increasing beta-receptor activity or 2) acutely changing adrenergic receptor conformation, affinity, or efficacy, such that beta-activity prevails.