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

TY - JOUR

T1 - Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

AU - Boushel, Robert Christopher

AU - Langberg, Henning

AU - Gemmer, Carsten

AU - Olesen, Jens Raabjerg

AU - Crameri, Regina

AU - Scheede, Celena

AU - Sander, Michael

AU - Kjaer, Michael

PY - 2002/9/1

Y1 - 2002/9/1

N2 - 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.

AB - 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.

KW - Coloring Agents

KW - Cyclooxygenase Inhibitors

KW - Drug Synergism

KW - Endothelium, Vascular

KW - Enzyme Inhibitors

KW - Exercise

KW - Humans

KW - Indocyanine Green

KW - Indomethacin

KW - Microcirculation

KW - Microdialysis

KW - Muscle, Skeletal

KW - NG-Nitroarginine Methyl Ester

KW - Nitric Oxide

KW - Nitric Oxide Synthase

KW - Prostaglandins

KW - Spectroscopy, Near-Infrared

KW - Vasodilation

M3 - Journal article

C2 - 12205200

SN - 0022-3751

VL - 543

SP - 691

EP - 698

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - Pt 2

ER -