Selective inhibition of cyclic adenosine monophosphate-mediated pulmonary vasodilation by acute hypoxia.

BACKGROUND

Adult respiratory distress syndrome is characterized by hypoxia and acute pulmonary hypertension. Therefore we examined the effect of acute hypoxia on the mechanisms of pulmonary vasodilation.

METHODS

Isolated rat pulmonary artery rings were suspended on tensiometers in a balanced salt solution. A normoxic gas mixture was bubbled through the solution (21% O2, 5% CO2, 74% N2). Rings were preconstricted with phenylephrine, and the following mechanisms of pulmonary vascular smooth muscle relaxation were studied in a random order: (1) endothelial-dependent cyclic guanosine monophosphate-mediated (acetylcholine, 10(-9) to 10(-6) mol/L), (2) endothelial-independent cyclic guanosine monophosphate-mediated (nitroprusside, 10(-9) to 10(-6) mol/L), and (3) beta-adrenergic receptor cyclic adenine monophosphate-mediated (isoproterenol, 10(-9) to 10(-6) mol/L). Separate rings were preconstricted with phenylephrine, and the gas was switched to a hypoxic mixture (0% O2, 5% CO2, 95% N2). After vasoconstriction to hypoxia reached a plateau, the response to the maximal effective dose of the above vasodilators (10(-6) mol/L) was determined in a random order. Statistical analysis was done with one-way analysis of variance with post hoc Bonferroni-Dunn correction. A p value of less than 0.05 was accepted as significant.

RESULTS

Endothelial-dependent and -independent cyclic guanosine monophosphate-mediated relaxation was the same in normoxia and hypoxia. On the other hand, hypoxia inhibited beta-adrenergic receptor cyclic adenine monophosphate-mediated pulmonary vasorelaxation (97.5% +/- 2.5% versus 71.5% +/- 2.3% in hypoxia; p < 0.01).

CONCLUSIONS

These data suggest that hypoxia selectively inhibits beta-adrenergic cyclic adenine monophosphate-mediated pulmonary vasorelaxation. This dysfunction of the normal mechanism of pulmonary vasodilation may contribute to the pulmonary hypertension seen in adult respiratory distress syndrome.