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Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis
C E King1, M J Melinyshyn, J D Mewburn
1Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Abstract:
The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used to determine whether the decrease in canine hindlimb blood flow (QL) with NOS inhibition would limit skeletal muscle O2 uptake (VO2). 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 perfusion pressure near the auto-perfused level. Six anesthetized dogs received L-NAME (20 mg/kg i.v.), whereas another group of five dogs received the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D-NAME 20 mg/kg i.v.). Efficacy of NOS inhibition was tested with intra-arterial boluses of acetylcholine. QL was measured continuously, and whole body and hindlimb VO2 were measured 60 and 120 min after L-NAME or D-NAME. Whole body VO2 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, QL fell 24% but VO2 increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg-1.min-1 (P < 0.05). No change in QL or VO2 occurred after D-NAME. NOS inhibition did not limit hindlimb VO2, despite decreases in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Nitric oxide synthase (NOS) inhibition with L-NAME reduced blood flow but did not limit skeletal muscle oxygen uptake (VO2) in canine hindlimbs. This suggests NOS inhibition does not impair muscle oxygen utilization despite reduced blood flow.
Area of Science:
- Physiology
- Pharmacology
- Cardiovascular Research
Background:
- Nitric oxide synthase (NOS) plays a role in regulating blood flow.
- The impact of NOS inhibition on skeletal muscle oxygen uptake (VO2) requires further investigation.
Purpose of the Study:
- To determine if NOS inhibition, using N omega-nitro-L-arginine methyl ester (L-NAME), limits canine hindlimb skeletal muscle VO2.
- To compare the effects of L-NAME with its stereospecific enantiomer, D-NAME.
Main Methods:
- Anesthetized dogs underwent hindlimb isolation with controlled perfusion.
- L-NAME or D-NAME was administered intravenously.
- Hindlimb blood flow (QL) and VO2 were measured following NOS inhibition.
Main Results:
- L-NAME administration significantly decreased cardiac output and hindlimb blood flow (QL).
- Despite reduced QL, hindlimb VO2 increased after L-NAME administration.
- D-NAME administration did not significantly alter QL or VO2.
Conclusions:
- NOS inhibition does not limit skeletal muscle oxygen uptake in the canine hindlimb.
- Reduced blood flow due to NOS inhibition does not impair muscle VO2 in this model.