TY - JOUR

T1 - Cyclo-oxygenase-2 mediated prostaglandin release regulates blood flow in connective tissue during mechanical loading in humans

AU - Langberg, H

AU - Boushel, Robert Christopher

AU - Skovgaard, D

AU - Risum, N

AU - Kjaer, M

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Mechanical loading is known to increase connective tissue blood flow of human tendons and to cause local release of vasodilatory substances. The present study investigated the importance of prostaglandins (PG) formed by cyclo-oxygenase isoforms (COX-1 and 2) for the exercise-related increase in blood flow in connective tissue. Healthy individuals (n = 24, age: 23-31 years) underwent 30 min of intermittent, isometric, plantarflexion with both calf muscles either without (n = 6, Control, C) or with blockade of PG formation, either COX-2 specific (n = 10, Celecoxib 2 x 100 mg day-1 for 3 days prior to the experiment) or COX unspecific (n = 8, indomethacin 100 mg (12 and 1 h pre-experiment) and acetyl salicylic acid 500 mg day-1 for 3 days pre-experiment). Prostaglandin E2 (PGE2) concentration was determined by microdialysis and blood flow by 133Xe washout. In C, interstitial PGE2 rose from (0.8 +/- 0.2 (rest) to 1.4 +/- 0.5 ng ml-1 (exercise), P <0.05), whereas during unspecific COX inhibition, tissue PGE2 was completely inhibited at rest and during exercise. COX-2 specific blockade did not inhibit tissue PGE2 at rest, but totally abolished the exercise induced increase. Blood flow was similar in the three groups at rest (P > 0.05), whereas the increase in flow with exercise was reduced by 35 and 43 % with COX-2 specific blockade (3.2 +/- 0.7 to 6.1 +/- 1.5 ml (100 g tissue)-1 min-1 or COX unspecific blockade (3.0 +/- 0.8 to 7.6 +/- 1.6), respectively, compared to C (2.7 +/- 0.8 to 10.2 +/- 2.0)(P <0.05). The findings indicate that COX-2 specific mechanisms are responsible for the exercise-induced increase in prostaglandin synthesis, and that increase in tissue prostaglandin plays an important role for blood flow in peritendinous connective tissue during physical loading in vivo.

AB - Mechanical loading is known to increase connective tissue blood flow of human tendons and to cause local release of vasodilatory substances. The present study investigated the importance of prostaglandins (PG) formed by cyclo-oxygenase isoforms (COX-1 and 2) for the exercise-related increase in blood flow in connective tissue. Healthy individuals (n = 24, age: 23-31 years) underwent 30 min of intermittent, isometric, plantarflexion with both calf muscles either without (n = 6, Control, C) or with blockade of PG formation, either COX-2 specific (n = 10, Celecoxib 2 x 100 mg day-1 for 3 days prior to the experiment) or COX unspecific (n = 8, indomethacin 100 mg (12 and 1 h pre-experiment) and acetyl salicylic acid 500 mg day-1 for 3 days pre-experiment). Prostaglandin E2 (PGE2) concentration was determined by microdialysis and blood flow by 133Xe washout. In C, interstitial PGE2 rose from (0.8 +/- 0.2 (rest) to 1.4 +/- 0.5 ng ml-1 (exercise), P <0.05), whereas during unspecific COX inhibition, tissue PGE2 was completely inhibited at rest and during exercise. COX-2 specific blockade did not inhibit tissue PGE2 at rest, but totally abolished the exercise induced increase. Blood flow was similar in the three groups at rest (P > 0.05), whereas the increase in flow with exercise was reduced by 35 and 43 % with COX-2 specific blockade (3.2 +/- 0.7 to 6.1 +/- 1.5 ml (100 g tissue)-1 min-1 or COX unspecific blockade (3.0 +/- 0.8 to 7.6 +/- 1.6), respectively, compared to C (2.7 +/- 0.8 to 10.2 +/- 2.0)(P <0.05). The findings indicate that COX-2 specific mechanisms are responsible for the exercise-induced increase in prostaglandin synthesis, and that increase in tissue prostaglandin plays an important role for blood flow in peritendinous connective tissue during physical loading in vivo.

KW - Achilles Tendon

KW - Adult

KW - Calibration

KW - Connective Tissue

KW - Cyclooxygenase 2

KW - Cyclooxygenase 2 Inhibitors

KW - Cyclooxygenase Inhibitors

KW - Dinoprostone

KW - Exercise

KW - Humans

KW - Immunohistochemistry

KW - Isoenzymes

KW - Leg

KW - Membrane Proteins

KW - Microdialysis

KW - Prostaglandin-Endoperoxide Synthases

KW - Prostaglandins

KW - Regional Blood Flow

KW - Rest

KW - Xenon

U2 - 10.1113/jphysiol.2003.046094

DO - 10.1113/jphysiol.2003.046094

M3 - Journal article

C2 - 12813143

VL - 551

SP - 683

EP - 689

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - Pt 2

ER -