title: Determinants of platelet activation in hypertensives with microalbuminuria.
abstract: 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.
authors.affiliation: Center of Excellence on Aging, G. d'Annunzio University Foundation, University of Chieti G. d'Annunzio Schools of Medicine and Pharmacy, Chieti, Italy
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Guagnano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Paoletti
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Manigrasso
authors.forename: Lea
authors.initials: L
authors.lastname: Pescara
authors.forename: Chiara
authors.initials: C
authors.lastname: Cuccurullo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: 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
chemical_list: 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