thromboxane-b2 and Renal-Artery-Obstruction

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

Topics: Adolescent; Adult; Aged; Angioplasty; Angiotensin II; Antioxidants; Biomarkers; Blood Glucose; Cholesterol; Cross-Sectional Studies; Dinoprost; F2-Isoprostanes; Female; Homocysteine; Humans; Hypertension; Hypertension, Renovascular; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Platelet Activation; Reference Values; Renal Artery Obstruction; Renin; Renin-Angiotensin System; Thromboxane B2; Triglycerides; Vitamins

Renal function can be severely impaired through injuries sustained after both short and prolonged periods of complete ischemia. The magnitude of renal dysfunction resulting from these conditions and their reversibility depend on the duration of anoxia. In this study, we used a Sprague-Dawley rat model (5 to 7 rats in each group) to study the pathogenesis of short-term ischemia (30, 60, and 120 min)/reperfusion (2, 4, 24 h, 1 wk, and 3 wk) injury of the kidney under warm (room temperature) or cold (4 degrees C) conditions. Ischemia was induced by clamping the renal artery. Changes in kidney weight, histopathology, concentrations of serum thromboxane and leukotriene, and tissue malonyldialdehyde (MDA) concentration, numbers of apoptotic bodies, and p53 expression in the kidney were compared with those of sham-operated rats. The results showed that the immediate increase in kidney weight due to inflammatory swelling was associated with simultaneous elevation of serum thromboxane and leukotriene levels. The changes in mediator levels were closely related to the duration of ischemia and temperature. Histologic structures were preserved better when renal artery clamping was done at 4 degrees C. MDA peroxidation products from the ischemic tissue prominently increased 1 week following ischemia; this paralleled a secondary increase in leukotriene levels. Flow cytometric detection of p53 oncoprotein showed a marked increase at 1 week following ischemia, which was accompanied by the development of apoptotic bodies in ischemic tissues. These changes were also closely related to the ischemic time and temperature during ischemia. This animal model may be useful for future studies of the prevention of ischemia/reperfusion injury of the kidney and for selection of effective antioxidants.

Topics: Animals; Apoptosis; Kidney; Leukotriene B4; Lipid Peroxidation; Organ Size; Rats; Rats, Sprague-Dawley; Renal Artery Obstruction; Reperfusion Injury; Thromboxane B2

Treatment with thromboxane (Tx) synthase inhibitors or free radical scavengers has been shown to afford protection from renal ischemia. Since free radicals are closely associated with thromboxane (Tx) synthesis, this study examines the thesis that free radical scavengers inhibit formation of Tx. Anesthetized rats (n = 42) underwent right nephrectomy. By random choice, before 45 min of left renal pedicle clamping, rats received: 0.5 ml dextrose placebo IV (n = 6); the hydroxyl radical scavenger dimethyl-thiourea (DMTU), 500 mg/kg IV (n = 10); or the superoxide scavenger superoxide dismutase (SOD), 24,000 Sigma Units (SU)/kg IV (n = 12). This dose of SOD was repeated before release of the clamp. Treatment with DMTU and SOD decreased plasma TxB2 levels following 5 min of reperfusion from 2,480 pg/ml in dextrose treated controls to 1,155 pg/ml (p less than 0.01) and 1,419 pg/ml (p less than 0.03), respectively. At 24 hr, DMTU and SOD therapy decreased creatinine from 3.0 mg/dl in controls to 1.6 mg/dl (p less than 0.01) and 2.1 mg/dl (p less than 0.05), respectively. At 24 hr, DMTU but not SOD decreased left renal weight from 113 to 94% (p less than 0.0003) of the weight of the previously removed right kidney, and histologically prevented acute tubular necrosis (p less than 0.05). In nephrectomized but nonischemic sham control rats (n = 7) plasma TxB2 and 6-keto-PGF1 alpha concentrations were 757 pg/ml and 82 pg/ml, creatinine level 0.9 mg/dl and kidney weight 94% of the previously removed right kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Kidney Injury; Animals; Epoprostenol; Humans; Kidney; Kidney Tubular Necrosis, Acute; Male; Rats; Renal Artery Obstruction; Superoxide Dismutase; Thiourea; Thromboxane B2; Thromboxane-A Synthase