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)B-2 and plasma P-selectin, in hypertensives with or without microalbuminuria, and its possible association with oxidative stress, by urinary 8-iso-prostaglandin (PG)F-2 alpha 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 nonnucroalbuminuric patients or controls (414 and 291 pg/mg, respectively: P<0.0001). Plasma P-selectin was 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-PGF(2 alpha), 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-PGF(2 alpha) 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-PGF(2 alpha), We conclude that lipid peroxidation is a major determinant of persistent platelet activation in hypertensive patients with microalbuminuria. (C) 2009 Elsevier Inc. All rights reserved.