Regulation of diaphragmatic oxygen uptake by endothelium-derived relaxing factor

The role of endogenous nitric oxide (NO) in the regulation of phrenic blood flow (Qphr) and O2 consumption (VO2) of the in situ isolated left hemidiaphragms was assessed in two groups of anesthetized, mechanically ventilated dogs. Saline was infused into the phrenic artery for 20 min in one group, whereas N omega-nitro-L-arginine (L-NNA, 6 x 10(-4) M) was infused in the other (L-NNA) group. Qphr and diaphragmatic VO2 were measured at rest and during 2 min of continuous 3-Hz stimulation of the left phrenic nerve. The animals were progressively hemorrhaged, and the measurements were repeated at various arterial pressures (Pa). For the resting diaphragm, Qphr at a mean Pa of 145 mmHg was lower in the L-NNA group than in the saline group; however, diaphragmatic VO2 values were similar in both groups. Qphr decreased with the decline in Pa in both groups, but O2 extraction ratios obtained at mean Pa of 25-45 mmHg were similar in both groups (71 vs. 73%). For the contracting diaphragm, Qphr and diaphragmatic VO2 values at a given Pa were lower in the L-NNA group than in the saline group (except at mean Pa < 75 mmHg). O2 extraction ratios obtained at a given Pa were similar in both groups. We concluded that 1) EDRF inhibition limits diaphragmatic blood flow both at rest and during 3-Hz stimulation; 2) diaphragmatic O2 extraction is unaffected by EDRF inhibition; and 3) the effect of EDRF release on diaphragmatic VO2 is dependent on the level of metabolic demands.