Regulation of pulmonary nitric oxide by carbon dioxide is intrinsic to thelung

Nitric oxide (NO) is present in exhaled air and is a regulator of airways a nd pulmonary vasculature. Exhaled NO can be depressed by inhaled carbon dio xide (CO2). To further characterize this, single-breath exhaled NO of rabbi ts was measured in vivo as well as in buffer-perfused lungs. Effects of bil ateral carotid occlusion or reduction of extracellular pH were also studied . During control conditions NO single-breath peaks in exhaled air in vivo w ere 25 +/- 1 parts per billion (p.p.b.) as compared with 79 +/- 13 p.p.b, i n the buffer-perfused lungs. Inhaled carbon dioxide (F-1 CO2 = 10%) within 10-20 s caused a depression of exhaled NO in vivo ito 21 +/- 1 p.p.b,. P < 0.05) and in perfused lungs ito 64 +/- 8 p.p.b., P < 0.05). In vivo, the CO 2-induced change in exhaled NO was unaffected by bilateral vagotomy, or by additional guanethidine treatment. Bilateral carotid occlusion did not affe ct exhaled NO. In perfused lungs, changes in pH (6.5-7.4) did not alter exh aled NO. Endogenous pulmonary nitric oxide production is thus measurable in single breaths in a small animal and is depressed by high airway concentra tion of carbon dioxide both in vivo and in the perfused rabbit lung. The ef fect by CO2 is independent of sympathetic outflow and the central nervous s ystem and is not caused by changes in extracellular pH. Carbon dioxide thus exerts a local regulatory effect on lung nitric oxide.