Decreased platelet nitric oxide contributes to increased circulating monocyte-platelet aggregates in hypertension.
OBJECTIVE
The aim of this study was to determine the effect of blood pressure (BP) on platelet nitric oxide (NO) signalling and on formation of circulating monocyte-platelet aggregates (MPA), as well as the role of platelet NO in modulating MPA in hypertension.


RESULTS
We first examined platelet NO signalling in 23 untreated hypertensive (UH) and 23 normotensive (NT) subjects. Platelets from hypertensives exhibited reduced NO synthase activation by albuterol or collagen, as well as suppressed basal and stimulated NO-attributable cyclic guanosine-3',5'-monophosphate, compared with NT. In a second study, comprising 106 subjects with a wide BP range, circulating MPA showed a strong positive correlation with BP. On multiple regression analysis, using a model incorporating systolic BP (SBP), diastolic BP, age, lipids, gender, and smoking status, the only independent predictor of MPA was SBP. Nitric oxide synthase inhibition with N(G)-monomethyl-L-arginine increased MPA in NT but not in hypertensives, whereas the NO donor spermine NONOate (SNO) decreased MPA in NT but not in hypertensives. Platelet P-selectin expression was higher in hypertensives than in NT, and its expression was suppressed by SNO in NT only.


CONCLUSIONS
Platelet NO production and responsiveness are suppressed with raised BP, and this may contribute to the increase in platelet P-selectin and hence in circulating MPA in hypertension.
Gkaliagkousi
Eugenia
E
Department of Clinical Pharmacology, Cardiovascular Division, King's College London, 3.07 Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Corrigall
Valerie
V
Becker
Silke
S
de Winter
Patricia
P
Shah
Ashish
A
Zamboulis
Chrysanthos
C
Ritter
James
J
Ferro
Albert
A
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008297:Male; D009000:Monocytes / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000172:deficiency*; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D019007:P-Selectin; C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine