CANINE HINDLIMB BLOOD-FLOW AND O-2 UPTAKE AFTER INHIBITION OF EDRF NOSYNTHESIS/

The nitric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine met hyl ester (L-NAME) was used to determine whether the decrease in canin e hindlimb blood flow (Q(L)) with NOS inhibition would limit skeletal muscle O-2 uptake (Vo(2)). Arterial inflow and venous outflow from the hindlimb were isolated, and the paw was excluded from the circulation . Pump perfusion from the right femoral artery kept the hindlimb perfu sion pressure near the autoperfused level. Six anesthetized dogs recei ved L-NAME (20 mg/kg iv), whereas another group of five dogs received the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D -NAME, 20 mg/kg iv). Efficacy of NOS inhibition was tested with intra- arterial boluses of acetylcholine. Q(L) was measured continuously, and whole body and hindlimb Vo(2) were measured 60 and 120 min after L-NA ME or D-NAME. Whole body iio, remained at control levels, but cardiac output decreased from 117 +/- 17 to 57 +/- 7 ml.kg(-1).min(-1) 60 min after L-NAME (P < 0.05) and remained at that level for the duration of the experiment. Cardiac output was significantly higher in the D-NAME group than in the L-NAME group at 60 min. After L-NAME, Q(L) fell 24% but Vo(2) increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg(-1).min(-1) (P < 0.05). No change in Q(L) or Vo(2) occurred after D-NAME. NOS inh ibition did not limit hindlimb Vo(2), despite decreases in blood flow. The surprising increase in hindlimb Vo(2) suggests that the role of e ndothelium-derived relaxing factor/NO in the regulation of skeletal mu scle blood flow must now be considered in conjunction with its associa ted effects on O-2 demand.