Dengue fever activates the L-arginine-nitric oxide pathway: an explanation for reduced aggregation of human platelets.
In patients with Dengue fever, a viral inflammatory syndrome, haemorrhage is a significant pathological feature, yet the underlying mechanisms remain unclear. Nitric oxide (NO) is an important regulator of platelet function, inhibiting aggregation, recruitment and adhesion to the vascular endothelium. We have investigated whether changes in the activity of the L-arginine-NO pathway in human platelets may account for increased bleeding in patients with Dengue fever. A total of 16 patients with Dengue fever and 18 age-matched healthy volunteers participated in the study. Collagen induced platelet aggregation in a dose-dependent manner in both Dengue patients and controls, but the degree of platelet aggregation was significantly reduced in the patient group. Elevated rates of L-arginine transport in Dengue fever patients were associated with enhanced NO synthase activity and elevated plasma fibrinogen levels. The present study provides the first evidence that Dengue fever is associated with increased L-arginine transport and NO generation and reduced platelet aggregation.
Mendes-Ribeiro
Antonio C
AC
Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. cribeiro@physiol.ox.ac.uk
Moss
Monique B
MB
Siqueira
Mariana As
MA
Moraes
Thalyta L
TL
Ellory
J Clive
JC
Mann
Giovanni E
GE
Brunini
Tatiana Mc
TM
D000328:Adult; D001120:Arginine / Q000378:metabolism* / Q000502:physiology; D001693:Biological Transport, Active / Q000502:physiology; D001791:Blood Platelet Disorders / Q000097:blood* / Q000378:metabolism; D003715:Dengue / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D010974:Platelet Aggregation / Q000502:physiology*; D010976:Platelet Count / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D009569:Nitric Oxide; D001120:Arginine