Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide.
The effects of hypercapnia (CO(2)) confined to either the alveolar space or the intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs. In blood-perfused lungs, when alveolar CO(2) concentration was increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular CO(2) levels increased Ppa without changes in exhaled NO. In buffer-perfused lungs, alveolar CO(2) increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min (P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min (P < 0.01). In contrast, intravascular CO(2) 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 reduction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypoxic 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 V(max) from 66.7 to 55.6 nl/min. These results suggest that alveolar CO(2) inhibits epithelial NO synthase activity noncompetitively and that the suppressed NO production by hypercapnia augments hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion matching.
Yamamoto
Y
Y
Department of Internal Medicine, School of Nursing, Asahikawa Medical College, Asahikawa 078-8510, Japan.
Nakano
H
H
Ide
H
H
Ogasa
T
T
Takahashi
T
T
Osanai
S
S
Kikuchi
K
K
Iwamoto
J
J
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002021:Buffers; D002245:Carbon Dioxide / Q000378:metabolism*; D015199:Extracorporeal Membrane Oxygenation; D006935:Hypercapnia / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000502:physiology*; D011817:Rabbits; D020545:Respiratory Mucosa / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
D002021:Buffers; D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen