Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease.
BACKGROUND
Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system.


RESULTS
We measured the urinary excretion of 8-iso-prostaglandin (PG) F2alpha 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-PGF2alpha 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-PGF2alpha 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-PGF2alpha after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2alpha 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.
Minuz
Pietro
P
Department of Biomedical and Surgical Sciences, University of Verona, Italy. pietro.minuz@mail.univr.it
Patrignani
Paola
P
Gaino
Stefania
S
Degan
Maurizio
M
Menapace
Laura
L
Tommasoli
Rosamaria
R
Seta
Francesca
F
Capone
Marta L
ML
Tacconelli
Stefania
S
Palatresi
Simone
S
Bencini
Chiara
C
Del Vecchio
Cecilia
C
Mansueto
Giancarlo
G
Arosio
Enrico
E
Santonastaso
Clara Lechi
CL
Lechi
Alessandro
A
Morganti
Alberto
A
Patrono
Carlo
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D017130:Angioplasty; D000804:Angiotensin II / Q000097:blood; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose; D002784:Cholesterol / Q000097:blood; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000503:physiopathology* / Q000652:urine; D006978:Hypertension, Renovascular / Q000209:etiology / Q000503:physiopathology / Q000601:surgery / Q000652:urine; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology; D012016:Reference Values; D012078:Renal Artery Obstruction / Q000150:complications / Q000503:physiopathology / Q000601:surgery; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D014280:Triglycerides / Q000097:blood; D014815:Vitamins / Q000097:blood
D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D028441:F2-Isoprostanes; D014280:Triglycerides; D014815:Vitamins; D006710:Homocysteine; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D002784:Cholesterol; D015237:Dinoprost; D012083:Renin