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Clinical Trial
. 2002 Sep 1;543(Pt 2):691-8.
doi: 10.1113/jphysiol.2002.021477.

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

Robert Boushel  1 , Henning Langberg, Carsten Gemmer, Jens Olesen, Regina Crameri, Celena Scheede, Michael Sander, Michael Kjaer
Affiliations
Clinical Trial

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

Robert Boushel et al. J Physiol. .

Abstract

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 +/- 0.8 ml (100 ml tissue)(-1) min(-1) at rest to 124 +/- 19, 245 +/- 24, 329 +/- 24 and 312 +/- 25 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 +/- 0.5 ml (100 ml tissue)(-1) min(-1) at rest, and 100 +/- 13, 163 +/- 21, 217 +/- 23 and 256 +/- 28 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45 and 60 W, respectively (P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.

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Figures

Figure 1
Figure 1. Quadriceps microvascular blood flow during exercise
Regional microvascular blood flow in the quadriceps muscles during incremental dynamic knee extension (upper panel). Blood flow in the vastus lateralis (middle panel) and vastus medialis (lower panel) in control knee extension (open symbols) and during combined NOS + PG blockade (filled symbols). Asterisks indicate difference between control and blockade conditions (P < 0.05).
Figure 2
Figure 2. Muscle ICG accumulation
A representative tracing of ICG accumulation patterns during exercise at 30 W in control conditions (continuous line), and during NOS + PG blockade (interrupted line).
Figure 3
Figure 3. Mixed femoral venous blood parameters
Femoral venous oxygen saturation (Sv,O2; upper left), oxygen pressure (Pv,O2; upper right), oxygen content (Cv,O2; middle left), potassium (K+; middle right), carbon dioxide pressure (Pv,CO2; lower left), and pH (lower right) at rest and during dynamic knee extension. Open symbols are control exercise and filled symbols are combined NOS + PG blockade. Asterisks indicate difference between control and blockade conditions (P < 0.05).
Figure 4
Figure 4. Systemic haemodynamics
Cardiac output (upper panel), mean arterial blood pressure (MAP; middle panel), and total peripheral resistance (TPR; lower panel), at rest and during incremental knee extension exercise. Open symbols are control exercise and filled symbols are combined NOS + PG blockade. Asterisks indicate difference between control and blockade conditions (P < 0.05).
See this image and copyright information in PMC

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