Determinants of platelet activation in hypertensives with microalbuminuria.
Microalbuminuria is a predictor of adverse outcome in hypertension.We evaluated in vivo platelet activation, by urinary 11-dehydrothromboxane (TX)B2 and plasma P-selectin, in hypertensives with or without microalbuminuria, and its possible association with oxidative stress, by urinary 8-iso-prostaglandin (PG)F2alpha and endothelial dysfunction. Sixty essential hypertensive patients, with (n=30) or without (n=30) microalbuminuria, and 30 controls were studied. Endothelial function was assessed by nitric oxide products, intercellular adhesion molecule (ICAM)-1, and asymmetric dimethylarginine (ADMA) levels. Urinary 11-dehydro-TXB2 excretion was higher in microalbuminuric (median 805 pg/mg creatinine) compared to nonmicroalbuminuric patients or controls (414 and 291 pg/mg, respectively; P<0.0001). Plasma P-selectinwas significantly higher in patients with microalbuminuria (median 136 ng/ml) as compared to those without microalbuminuria or controls (85 and 65 ng/ml; P<0.0001). Urinary 8-iso-PGF2alpha excretion was also enhanced in microalbuminuric (median 279 pg/mg creatinine) compared to nonmicroalbuminuric patients or controls (157 and 146 pg/mg, respectively; P<0.0001). A significant impairment in endothelial function was found in microalbuminuric patients, with decreased nitric oxide and increased ICAM-1 and ADMA levels. Multivariate regression analysis showed that urinary 8-iso-PGF2alpha excretion (beta=0.49; P<0.0001) and microalbuminuria (beta=0.36; P<0.001) were independently related to 11-dehydro-TXB2 in hypertensives. Vitamin E supplementation (900 mg daily for 1 month) in 10 hypertensives with microalbuminuria was associated with normalization in median 11-dehydro-TXB2 and 8-iso-PGF2alpha. We conclude that lipid peroxidation is a major determinant of persistent platelet activation in hypertensive patients with microalbuminuria.
Guagnano
Maria Teresa
MT
Center of Excellence on Aging, G. d'Annunzio University Foundation, University of Chieti G. d'Annunzio Schools of Medicine and Pharmacy, Chieti, Italy
Ferroni
Patrizia
P
Santilli
Francesca
F
Paoletti
Vincenzo
V
Manigrasso
Maria Rosaria
MR
Pescara
Lea
L
Cuccurullo
Chiara
C
Ciabattoni
Giovanni
G
Davì
Giovanni
G
D000368:Aged; D000419:Albuminuria; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000652:urine; D018450:Disease Progression; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D019007:P-Selectin / Q000097:blood*; D015539:Platelet Activation / Q000502:physiology*; D011454:Prostaglandins A / Q000652:urine*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D014810:Vitamin E / Q000008:administration & dosage
C117466:8-isoprostaglandin A2; D015415:Biomarkers; D019007:P-Selectin; D011454:Prostaglandins A; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; D009569:Nitric Oxide; D013929:Thromboxane B2; C018524:N,N-dimethylarginine; C049235:11-dehydro-thromboxane B2; D001120:Arginine