Regulation of pulmonary nitric oxide by carbon dioxide is intrinsic to the lung.

Abstract

Nitric oxide (NO) is present in exhaled air and is a regulator of airways and pulmonary vasculature. Exhaled NO can be depressed by inhaled carbon dioxide (CO2). To further characterize this, single-breath exhaled NO of rabbits was measured in vivo as well as in buffer-perfused lungs. Effects of bilateral carotid occlusion or reduction of extracellular pH were also studied. During control conditions NO single-breath peaks in exhaled air in vivo were 25 +/- 1 parts per billion (p.p.b.) as compared with 79 +/- 13 p.p.b. in the buffer-perfused lungs. Inhaled carbon dioxide (FI co2=10%) within 10-20 s caused a depression of exhaled NO in vivo (to 21 +/- 1 p.p.b., P < 0.05) and in perfused lungs (to 64 +/- 8 p.p.b., P < 0. 05). In vivo, the CO2-induced change in exhaled NO was unaffected by bilateral vagotomy, or by additional guanethidine treatment. Bilateral carotid occlusion did not affect exhaled NO. In perfused lungs, changes in pH (6.5-7.4) did not alter exhaled NO. Endogenous pulmonary nitric oxide production is thus measurable in single breaths in a small animal and is depressed by high airway concentration of carbon dioxide both in vivo and in the perfused rabbit lung. The effect by CO2 is independent of sympathetic outflow and the central nervous system and is not caused by changes in extracellular pH. Carbon dioxide thus exerts a local regulatory effect on lung nitric oxide.