Platelet aggregation in arterial hypertension: is there a nitric oxide-urea connection?
1. Systemic arterial hypertension (SAH) is a major independent risk factor for cardiovascular disease. The physiopathology of SAH is multifactorial, complex and remains to be elucidated. Nitric oxide (NO) is an important regulator of vascular and haemostatic functions. The cationic amino acid l-arginine serves as the substrate for NO synthases (NOS) and arginase, an enzyme of the urea cycle. We have previously reported inhibition of l-arginine transport in erythrocytes and platelets in hypertension. 2. The aim of the present study was to investigate the l-arginine-NO pathway and urea cycle in platelets and their role in platelet function and systemic inflammatory responses in SAH patients. The expression and activity of NOS and arginase in platelets, platelet aggregation and plasma levels of C-reactive protein (CRP) were evaluated in 20 SAH patients and 18 age-matched healthy volunteers. 3. There was a reduction of NOS activity in hypertensive patients that was associated with activation of platelet aggregability induced by collagen, but not by ADP. Platelets from SAH patients exhibited compensatory overexpression of inducible NOS, but not endothelial NOS. Intraplatelet arginase activity in SAH patients was not affected, but systemic concentrations of CRP were increased compared with controls. 4. It is likely that diminished NO bioavailability in SAH contributes to cardiovascular complications. Our findings may provide the basis for developing new therapeutic approaches for the treatment of hypertension.
Moss
Monique B
MB
Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Siqueira
Mariana A
MA
Mann
Giovanni E
GE
Brunini
Tatiana Mc
TM
Mendes-Ribeiro
Antônio C
AC
D000328:Adult; D001119:Arginase / Q000032:analysis; D001120:Arginine / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002097:C-Reactive Protein / Q000032:analysis; D003094:Collagen / Q000032:analysis; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010974:Platelet Aggregation; D014508:Urea / Q000378:metabolism*
D009569:Nitric Oxide; D014508:Urea; D003094:Collagen; D002097:C-Reactive Protein; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase