Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide

The effects of hypercapnia (CO2) confined to either the alveolar space or t he intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metab olites (NOx), and pulmonary arterial pressure (Ppa) were examined during no rmoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfuse d rabbit lungs. In blood-perfused lungs, when alveolar CO2 concentration wa s increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Inc rements of intravascular CO2 levels increased Ppa without changes in exhale d NO. In buffer-perfused lungs, alveolar CO2 increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min (P < 0.01) and perfusate N Ox from 4.8 to 1.8 nmol/min (P < 0.01). In contrast, intravascular CO2 did not affect either exhaled NO or Ppa despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa by 28% from baseline with a redu ction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypox ic Ppa response up to 50% with a further decline in exhaled NO. Hypercapnia did not alter the apparent K-m for O-2, whereas it significantly decreased the Vmax from 66.7 to 55.6 nl/min. These results suggest that alveolar CO2 inhibits epithelial NO synthase activity noncompetitively and that the sup pressed NO production by hypercapnia augments hypoxic pulmonary vasoconstri ction, resulting in improved ventilation-perfusion matching.