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(Circulation. 2002;106:2800.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Increased Oxidative Stress and Platelet Activation in Patients With Hypertension and Renovascular Disease

Pietro Minuz, MD; Paola Patrignani, PhD; Stefania Gaino, MD; Maurizio Degan, BS; Laura Menapace, MD; Rosamaria Tommasoli, BS; Francesca Seta, DPharm; Marta L. Capone, DPharm; Stefania Tacconelli, DPharm; Simone Palatresi, MD; Chiara Bencini, MD; Cecilia Del Vecchio, MD; Giancarlo Mansueto, MD; Enrico Arosio, MD; Clara Lechi Santonastaso, MD; Alessandro Lechi, MD; Alberto Morganti, MD; Carlo Patrono, MD

From the Department of Biomedical and Surgical Sciences, University of Verona (P.M., S.G., M.D., L.M., R.T., G.M., E.A., C.L.S., A.L.); the Center of Excellence on Aging, "G. D’Annunzio" University of Chieti (P.P., F.S., M.L.C, S.T., C.P.); the Institute of Clinical Medicine and Physiology, University of Milan (S.P., C.B., C.D.V., A.M.); and the Department of Pharmacology, "La Sapienza" University of Rome (C.P.), Italy.

Correspondence to Pietro Minuz, MD, Medicina Interna C, Policlinico GB Rossi, 37134 Verona, Italy. E-mail pietro.minuz{at}mail.univr.it

Background— Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system.

Methods and Results— We measured the urinary excretion of 8-iso-prostaglandin (PG) F₂ and 11-dehydro-thromboxane (TX) B₂ as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF₂ was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB₂ was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF₂ correlated with 11-dehydro-TXB₂ (r_s=0.48; P<0.05) and renal vein renin (r_s=0.67; P<0.005) and angiotensin II (r_s=0.65; P=0.005) ratios. A reduction in 8-iso-PGF₂ after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF₂ were related to baseline lipid peroxidation (r_s=-0.73; P<0.001), renal vein angiotensin II (r_s=-0.70; P<0.01) and renin (r_s=-0.63; P<0.05) ratios.

Conclusions— Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.

Key Words: thromboxane • stenosis • hypertension • renin • angiotensin

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