Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system.
Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-α) plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.
Cardiovascular Research, Institute of Physiology .
Simon F
SF
Stämpfli
Giovanni G
GG
Camici
Stephan
S
Keller
Izabela
I
Rozenberg
Margarete
M
Arras
Beat
B
Schuler
Max
M
Gassmann
Irene
I
Garcia
Thomas F
TF
Lüscher
Felix C
FC
Tanner
D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016627:Oxidopamine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor; D012039:Regional Blood Flow; D012149:Restraint, Physical; D013315:Stress, Psychological; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013925:Thromboplastin / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology*
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D016627:Oxidopamine; D013925:Thromboplastin; D000068800:Etanercept