ROLE OF NITRIC-OXIDE IN THE REGULATION OF OXYGEN-CONSUMPTION IN CONSCIOUS DOGS

The role of nitric oxide (NO) in the regulation of O-2 consumption was studied in chronically instrumented conscious dogs. A specific NO synthesis inhibitor, nitro-L-arginine (NLA, 30 mg/kg IV), significantly increased mean arterial pressure from 100+/-4 to 134+/-5 mm Hg (mean+/-SEM) and total peripheral resistance by 157+/-16% and reduced cardiac output by 47+/-3% and heart rate by 34+/-6% after 120 minutes. Changes in arterial blood gases were not observed. There were significant changes in Po-2 (-14+/-2 mm Hg), O-2 saturation (-21+/-2%), the percentage of hemoglobin as oxyhemoglobin (-21+/-2%), and O-2 content (-3.0+/-0.9 vol%) and a significant increase in percent reduced hemoglobin (21+/-1%) in mixed venous blood, associated with an increase in O-2 extraction (5.1+/-0.2 vol%) (all P<.01). O-2 consumption was increased from 124+/-6 to 155+/-9 mL/min (P<.05). Methoxamine, titrated to have hemodynamic effects similar to those of NLA (eg, mean arterial pressure increased from 97+/-4 to 131+/-5 mm Hg), had much smaller effects on venous blood gases, hemoglobin, and O-2 extraction (2.3+/-0.7 vol%) and no significant effect on O-2 consumption. NLA also caused an increase in O-2 consumption of 37+/-8% (P<.01) in quietly resting conscious dogs that had undergone pretreatment with hexamethonium and atropine, but no significant change in O-2 consumption in dogs anesthetized with barbiturate. Our results suggest that basal constitutive NO release has an impor tant function in the regulation of tissue oxygenation; perhaps NO production by capillary endothelium regulates mitochondrial function in adjacent parenchymal cells in peripheral tissues.