Affiliation:
1. 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.
Abstract
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) F
2α
and 11-dehydro-thromboxane (TX) B
2
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-PGF
2α
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-TXB
2
was also significantly higher in RVD patients compared with healthy subjects. In RVD patients
,
urinary 8-iso-PGF
2α
correlated with 11-dehydro-TXB
2
(
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-PGF
2α
after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF
2α
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
194 articles.
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