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

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 2␣ 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 2␣ 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 2␣ correlated with 11-dehydro-TXB 2 (r s ϭ0.

l -Arginine Reverses p47phox and gp91phox Expression Induced by High Salt in Dahl Rats

“…49 Enhanced formation of 8-isoprostane has been associated with several cardiovascular risk factors 50 and has been found to correlate with in vivo thromboxane A 2 biosynthesis. 39,45 In line with these reports, we previously reported that high salt induces acetylcholine-induced contraction caused by endotheliumderived contraction factor, which may be thromboxane A 2 and/or prostaglandin H 2 , in carotid and renal arterial rings but not aorta of hypertensive DS rats, 19 and L-arginine supplementation diminished the contraction. 20 Actually, we showed in this study that high salt loading increases urinary thromboxane B 2 (a stable metabolite of thromboxane A 2 ) excretion ( Figure 7B), which was reduced by L-arginine supplementation.…”

“…45 A recently discovered series of prostaglandin F2-like compound, 8-isoprostane, are produced in vivo nonenzymatically by free radical catalyzed peroxidation of arachidonic acid 46 in cell membranes and in circulating LDL. 38,47 High Figure 6.…”

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE −/− Mice With Unilateral Renal Artery Stenosis

“…The elevation of Ang‐II levels observed 15 days after surgery in mice with chronic RAS in the current study was in contrast to the persistent reduction in Ang‐II levels observed in mice that had restoration of renal blood flow. Other mechanisms that have been shown to contribute to atheroma formation in various models of RAS and which may be modulated by a reduction in the time of renal ischemia include regulation of nitric oxide levels, generation of reactive oxygen species, low‐density lipoprotein oxidation, and upregulation of early growth response‐1, an immediate early gene product and zinc finger transcription factor that has been implicated in atherogenesis 13, 25, 26…”

“…Biological plausibility of this hypothesis is provided by numerous studies showing that decreased renal perfusion is associated with RAS activation,5 and data from animal models showing that even short‐term elevation in angiotensin II (Ang‐II) levels can accelerate the development of atherosclerosis and lead to changes in the arterial wall that persist even after Ang‐II levels return to baseline 6, 7, 8, 9, 10, 11. In addition, RAS has been shown to result in elevated oxidative stress, sympathoadrenergic activation, and impaired vasoactive responses, both within the kidney and the systemic microcirculation 12, 13…”

Urinary 8-iso-Prostaglandin F 2α as a Risk Marker in Patients With Coronary Heart Disease

“…A growing body of evidence has been provided by several groups underlining the validity of the isoprostanes as in vivo markers of oxidative stress. 3,6,7 Studies have suggested isoprostanes as markers for patients at risk of atherosclerosis and coronary heart disease (CHD): elevated isoprostane formation was found in underlying diseases such as diabetes mellitus, 8 hypertension and renovascular disease, 9 hyperlipidemia, 10 obesity, 11 and cigarette smoking. 12 The major risk factors for CHD are elevated blood pressure, elevated total cholesterol, LDL cholesterol, HDL cholesterol, diabetes mellitus, obesity, cigarette smoking, and advancing age.…”