Acidosis stimulates nitric oxide production and lung damage in rats

Systemic hypotension during sepsis is thought to be due to nitric oxide (NO ) overproduction, but it may also be due to acidosis. We evaluated in healt hy rats the consequences of acid infusion on NO and blood pressure. Sprague -Dawley rats were anesthetized, and ventilated with room air. The animals w ere randomized into four groups. Group 1 (C, n = 10) received only normal s aline at rates comparable to the other groups. Group 2 (A1, n = 10) receive d hydrochloric acid at 0.162 mmol in the first 15 to 30 min, followed by a continuous infusion of 0.058 mmol/h for 5 h. Group 3 (AG+A1, n = 6) was pre treated with aminoguanidine (AG, 50 mg/kg), and HCl was infused as above. G roup 4 (A2, n = 7) received HCl at twice the rate used in Al. Nitric oxide concentration in the exhaled gas (ENO), blood gases, and mean arterial pres sure were measured every 30 min. Acid infusion in A1 caused the pH to fall gradually from 7.43 +/- 0.01 to 7.13 +/- 0.05. This moderate decrease in pH was associated with a marked increase in ENO (1.6 +/- 0.3 to 114.2 +/- 22. 3 ppb), an increase in plasma nitrite/nitrate (17.3 +/- 3.7 to 35.2 +/- 4.3 mu M), and a significant decrease in blood pressure (110.5 +/- 6.3 to 63.3 +/- 15.0 mm Hg). Furthermore, acidosis caused lung inflammation, as sugges ted by the increase in lung myeloperoxidase activity (282.2 +/- 24.7 to 679 .3 +/- 57.3 U/min/g) and lung injury score (1.7 +/- 0.2 to 3.5 +/- 0.6). Ac idosis after AG pretreatment was associated with a similar change in pH, bu t the increase in ENO, nitrite/nitrate, and systemic hypotension were preve nted. Furthermore, lung injury was attenuated by AG, as suggested by a towe r myeloperoxidase activity, though lung injury score was not altered. In th is model, moderate acidosis causes increases in NO, hypotension, and lung i nflammation. Lung inflammation and injury are due in part to acidosis and N O production. This is the first report to show a direct effect of chronic a cidosis on NO production and lung injury. These results have profound impli cations on the role of acidosis on NO production and lung injury during sep sis.