Effect of inhibition of nitric oxide release on the diaphragmatic oxygen delivery-consumption relationship

In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, the hypothesis that nitric oxide (NO) is an important regulator of diaphragmatic O2 extraction was tested.

The effect of an intra-arterial infusion of an NO-synthase inhibitor NG-nitro-L-arginine (L-NA) on the critical O2 delivery (QO2c), below which O2 consumption becomes dependent on O2 supply, was assessed in two groups of animals in which either saline or L-NA (6 x 10(-4) mol/L) was infused into the phrenic artery over 20 minutes. The diaphragm was then perfused either by left femoral arterial blood (autoperfusion) or by pump perfusion with blood from the femoral artery. QO2 was reduced by stepwise hemorrhage in the autoperfusion groups and by reducing the pump rate in the pump perfusion groups.

During autoperfusion, QO2c in the saline- and L-NA-treated groups was not different (0.88 +/- 0.15 and 0.98 +/- 0.12 mL/min/100 g, respectively) for the resting diaphragm. Critical O2 extraction ratios were not different (64.5% +/- 9.9% and 67.8% +/- 6.4%, respectively). In the saline group, QO2c during 3-Hz stimulation was 5.03 +/- 0.9 mL/min/100 g. In the L-NA group, diaphragm flow was lower than the saline group, and no QO2c was found. In the pump-perfused contracting diaphragm, QO2c in both groups did not differ (3.1 +/- 0.5 and 4.05 +/- 0.65 mL/min/100 g, respectively). O2 extraction ratios at these O2 deliveries were different (63.3% +/- 5.2% and 77.4% +/- 4.3%, respectively). However, NO-synthase inhibiton had no effect on maximum diaphragmatic O2 extraction ratio.

These results indicate that NO release is an important modulator of the tone of diaphragmatic resistance vessels, but it does not appear to regulate the processes by which O2 extraction is enhanced to compensate for decreased O2 delivery.