SELECTIVE-INHIBITION OF CYCLIC ADENOSINE MONOPHOSPHATE-MEDIATED PULMONARY VASODILATION BY ACUTE-HYPOXIA

Background. Adult respiratory distress syndrome is characterized by hy poxia and acute pulmonary hypertension. Therefore we examined the effe ct of acute hypoxia on the mechanisms of pulmonary vasodilation. Metho ds. Isolated rat pulmonary artery rings were suspended on tensiometers in a balanced salt solution. A normoxic gas mixture was bubbled throu gh the solution (21% O-2, 5% CO2, 74% N-2. Rings were preconstricted w ith phenylephrine, and the following mechanisms of pulmonary vascular smooth muscle relaxation were studied in a random order: (1) endotheli al-dependent cyclic guanosine monophosphate-mediated (acetylcholine, 1 0(-9) to 10(-6) mol/L), (2) endothelial-independent cyclic guanosine m onophosphate-mediated (nitroprusside, 10(-9) to 10(-6) mol/L), and (3) beta-adrenergic receptor cyclic adenine monophosphate-mediated (isopr oterenol, 10(-9) to 10(-6) mol/L). Separate rings were preconstricted with phenylephrine, and the gas was switched to a hypoxic mixture (0% O-2, 5% CO2, 95% N-2). After vasoconstriction to hypoxia reached a pla teau, the response to the maximal effective dose of the above vasodila tors (10(-6) mol/L) was determined in a random order. Statistical anal ysis was done with one-way analysis of variance with post hoc Bonjferr oni-Dunn correction. A p value of less than 0.05 was accepted as signi ficant. Results. Endothelial-dependent and -independent cyclic guanosi ne monophoshate-mediafed relaxation was the same in normoxia and hypox ia. On the other hand, hypoxia inhibited beta-adrenergic receptor cycl ic adenine monophosphate-mediated pubmonary vasorelaxation (97.5% +/- 2.5% versus 71.5% +/- 2.3% in hypoxia; p < 0.01). Conclusions. These d ata suggest that hypoxia selectively inhibits beta-adrenergic cyclic a denine monophosphate-mediated pulmonary vasorelaxation. This dysfuncti on of the normal mechanism of pulmonary vasodilation may contribute to the pulmonary hypertension seen in adult respiratory distress syndrom e.