Influence of aspirin and indomethacin on variability of alveolar hypoxic vasoconstriction

Alveolar hypoxia induces pulmonary vasoconstriction but the strength of alveolar hypoxic vasoconstriction (AHV) is variable even within the same species. The influence of aspirin and indomethacin, cyclo-oxygenase inhibitors, was examined in two groups of dogs, those with weak AHV and those with vigorous AHV. A double-lumen endotracheal tube allowed ventilation of one lung with nitrogen as an alveolar hypoxic stimulus and ventilation of the other lung with O2 to maintain systemic oxygenation. Perfusion to each lung was measured with xenon-133 and external counters. In weak reactors both aspirin and indomethacin induced fourfold enhancement of AHV (P less than 0.01), whereas no significant influence on vigorous reactors was noted. Cyclo-oxygenase inhibitors also produced enhanced reactivity in the isolated lung to alveolar hypoxia and prostaglandin F2alpha but not to angiotensin II and norepinephrine. Aspirin-enhanced AHV in the isolated lung could not be diminished with blockade of angiotensin II receptors or of alpha receptors. In summary, weak AHV in intact or isolated dog lung may be due to an excess of a prostaglandin or prostacyclin vasodilator.