Generation of 8‐epi‐prostaglandin F<sub>2α</sub> in isolated rat kidney glomeruli by a radical‐independent mechanism

Klein, Thomas; Neuhaus, Katrin; Reutter, Felix; Nüsing, Rolf M.

doi:10.1038/sj.bjp.0704111

Cited by 29 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the sustained increase in 8-Iso detected after 1 wk of ANG II administration likely represents increased generation. Isoprostanes also can be generated enzymically by cyclooxygenase-1 in platelets (34) or cyclooxygenase-2 in monocytes (32) or isolated glomeruli (18). However, we found the same pattern of changes in excretion of 8-Iso and MDA that is not Fig.…”

Section: Because Our Antibodies To Gp91contrasting

confidence: 36%

Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression

Chabrashvili

Kitiyakara

Blau

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

290

288

View full text Add to dashboard Cite

Oxidative stress accompanies angiotensin (ANG) II infusion, but the role of ANG type 1 vs. type 2 receptors (AT 1-R and AT2-R, respectively) is unknown. We infused ANG II subcutaneously in rats for 1 wk. Excretion of 8-isoprostaglandin F 2␣ (8-Iso) and malonyldialdehyde (MDA) were related to renal cortical mRNA abundance for subunits of NADPH oxidase and superoxide dismutases (SODs) using real-time PCR. Subsets of ANG II-infused rats were given the AT 1-R antagonist candesartan cilexetil (Cand) or the AT 2-R antagonist PD-123,319 (PD). Compared to vehicle (Veh), ANG II increased 8-Iso excretion by 41% (Veh, 5.4 Ϯ 0.8 vs. ANG II, 7.6 Ϯ 0.5 pg/24 h; P Ͻ 0.05). This was prevented by Cand (5.6 Ϯ 0.5 pg/24 h; P Ͻ 0.05) and increased by PD (15.8 Ϯ 2.0 pg/24 h; P Ͻ 0.005). There were similar changes in MDA excretion. Compared to Veh, ANG II significantly (P Ͻ 0.005) increased the renal cortical mRNA expression of p22 phox (twofold), Nox-1 (2.6-fold), and Mn-SOD (1.5-fold) and decreased expression of Nox-4 (2.1-fold) and extracellular (EC)-SOD (2.1-fold). Cand prevented all of these changes except for the increase in Mn-SOD. PD accentuated changes in p22 phox and Nox-1 and increased p67 phox . We conclude that ANG II infusion stimulates oxidative stress via AT 1-R, which increases the renal cortical mRNA expression of p22 phox and Nox-1 and reduces abundance of Nox-4 and EC-SOD. This is offset by strong protective effects of AT 2-R, which are accompanied by decreased expression of p22 phox , Nox-1, and p67 phox . O 2 Ϫ ⅐ interacts with esterified or free arachidonate to yield a family of isoprostanes that includes 8-isoprostane prostaglandin F 2␣ (8-Iso). The steady-state excretion of 8-Iso reflects oxidative stress (38). There is evidence of enhanced oxidative stress during prolonged infusion of ANG II (36) and in models of ANG IIdependent hypertension (2,8,22,24,48). However, the roles of AT 1 -R vs. AT 2 -R in the generation of oxidative stress and the expression of NADPH oxidase and SOD in kidneys has not been established.The first aim of this study was to determine the effects of AT 1 -and AT 2 -R blockade on the excretion of 8-Iso during a "slow-pressor" dose of ANG II. Because isoprostanes also can be generated by metabolism of arachidonate via cyclooxygenase (19,33), additional studies assessed the excretion of an arachidonate-independent marker of lipid peroxidation, malonyldialdehyde (MDA). The second aim was to investigate the effects of these perturbations on the renal expression of the mRNAs for the components of NADPH oxidase and SOD isoforms.

show abstract

Section: Because Our Antibodies To Gp91contrasting

confidence: 36%

Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression

Chabrashvili

Kitiyakara

Blau

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

290

288

View full text Add to dashboard Cite

show abstract

“…Urine isoprostanes are considered a reliable marker to quantify systemic oxidative stress (30). However, recent reports indicate that in rats, under certain conditions such as increased oxygen tension (26) or NADPH-stimulated free radical production (15), F 2␣ isoprostanes were not increased, although other oxidative stress parameters were elevated. Although this study does not provide data to support this hypothesis, it is possible that the increased vascular superoxide production mainly originates from a vascular NAD(P)H oxidase (18,35) and hence isoprostanes F 2␣ could not accurately reflect the increased aortic oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity

Dobrian

Schriver

Lynch

et al. 2003

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

. Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity. Am J Physiol Renal Physiol 285: F619-F628, 2003. First published June 10, 2003 10.1152 10. /ajprenal.00388. 2002 diet is known to induce or aggravate hypertension in animal models of hypertension and in humans. When Sprague-Dawley rats (n ϭ 60) are fed a moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half develop obesity [obesity prone (OP)] and mild hypertension, whereas the other half [obesity resistant (OR)] maintain body weight equivalent to a low-fat control (C) and are normotensive. The aim of this study was to test the effect of high-NaCl diets (2 and 4% NaCl) on the development of hypertension and obesity, oxidative stress, and renal function. Both 2 and 4% NaCl induced an early increase in systolic blood pressure of OP but not OR or C rats. High-salt intake induced an increase in the size and reduction in number of adipocytes, concomitant to a twofold increase in circulating leptin in OP rats. Aortic superoxide generation indicated a 2.8-fold increase in the OP high-salt vs. normalsalt groups, whereas urine isoprostanes were not significantly increased. Also, hydroxynonenal protein adducts in the kidney were highly increased in OP rats on 2 and 4% NaCl, indicating oxidative stress in the renal tissue. Urine albumin was increased threefold in the OP on 2% NaCl and fourfold in the same group on 4% NaCl vs. 0.8% NaCl. Kidney histology indicated a higher degree of glomerulosclerosis in OP rats on high-salt diets. In summary, high-salt diet accelerated the development but did not increase the severity of hypertension; high salt increased oxidative stress in the vasculature and kidney and induced kidney glomerulosclerosis and microalbuminuria. Also, the OP rats on high salt displayed adipocyte hypertrophy and increased leptin production.glomerulosclerosis; kidney; leptin; sodium dietary OBESITY IS A complex, multifactorial disease that is associated with essential hypertension in ϳ78% of men and ϳ65% of women, as indicated by the data from the Framingham Heart Study (25). Another important contributor to hypertension in humans is the excessive consumption of dietary salt, and epidemiological studies have demonstrated a significant but weak relation between salt intake and hypertension (32, 33). Some, but not all, interventional studies have shown that salt restriction may lower blood pressure (BP) (19,33). Some recent studies report correlation among hypertension, salt sensitivity, and insulin resistance in obese humans (38), whereas others fail to observe a significant relationship (8). Animal models of obesity, hypertension, and insulin resistance display differences with respect to salt sensitivity. In Zucker rats, there is a clear correlation between salt intake and the severity of hypertension (4, 47), whereas in chronic hyperinsulinemic Sprague-Dawley (SD) rats, hypertension is not salt sensitive, albeit a shift in pressure-natriuresis relationship was reported (2). One important cont...

show abstract

“…Also, inhibition of basal NO production by eNOS induces vascular constriction and decreases cortical and medullary blood flow. This might decrease O 2 supply and/or alter O 2 consumption, leading to renal hypoxia [27].…”

Section: Discussionmentioning

confidence: 99%

“…2-Amino-4-methylpyridine plus CDDP-treated rats showed significant decreases in the kidney GSH-Px activity and MDA production level in comparison with those animals treated with CDDP alone, as well as increased platinum accumulation in the kidney tissue. Inhibition of eNOS reduces the basal NO responsible for maintaining the relatively low vascular resistance that is characteristic for the kidney, causing vasoconstriction and promoting tissue ischaemia, which exacerbates tissue injury [27] with a progressive fall in the ratio of vasodilator to vasoconstrictor eicosanoids [34]. These effects occur in conjugation with increased plasma renin activity, increased aldosterone concentration and decreased atrial natriuretic peptide [8].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nitric Oxide Synthase Aggravates Cisplatin-Induced Nephrotoxicity: Effect of 2-Amino-4-Methylpyridine

Saad¹,

Najjar²,

Daba³

et al. 2002

Chemotherapy

View full text Add to dashboard Cite

Background: Nitric oxide (NO) has been shown to play a role in maintaining normal renal function. However, the role of NO in cisplatin (CDDP)-induced nephrotoxicity is still unclear. The aim of the present work was to examine the effect of the NO synthase (NOS) inhibitor, 2-amino-4-methylpyridine, on the severity of CDDP-induced nephrotoxicity. Methods: Male Wistar rats were divided into six groups. Three control groups received plain drinking water or water containing 1.5% L-arginine. One of the two groups receiving plain water was treated with an intraperitoneal injection of 2-amino-4-methylpyridine (1 mg/kg in normal saline), and the other two control groups were injected intraperitoneally with normal saline. Another three groups were treated in the same manner and injected with CDDP (6 mg/kg, i.p.). CDDP was injected 1 h after 2-amino-4-methylpyridine treatment. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analysed. Results: CDDP-treated rats showed increases in the kidney weight as a percentage of the total body weight and serum creatinine and urea levels and decreases in serum albumin and calcium levels. Also, CDDP treatment induced reductions in the kidney total nitrate/nitrite (NO_x), reduced glutathione (GSH) and glutathione peroxidase activity (GSH-Px) levels and an increase in the kidney malondialdehyde (MDA) production level. In contrast, 2-amino-4-methylpyridine treatment 1 h prior to CDDP injection induced marked exacerbation of CDDP-induced nephrotoxicity, as manifested by severe aggravation of the indices of nephrotoxicity. Also, 2-amino-4-methylpyridine plus CDDP-treated rats showed exaggeration of the reduction in the kidney total NO_x content and GSH-Px activity and elevation of the kidney platinum accumulation level with normalization of the kidney MDA production level and rebound in the kidney GSH content. Histopathologically, CDDP-treated rats showed marked interstitial nephritis, tubular atrophy and tubular necrosis. However, treatment with 2-amino-4-methylpyridine 1 h prior to CDDP injection revealed marked exacerbation of CDDP-induced histopathological changes. Conclusions: The present findings suggest that NO plays a role in CDDP-induced nephrotoxicity. Administration of 2-amino-4-methylpyridine, an NOS inhibitor, exacerbates CDDP-induced nephrotoxicity.

show abstract

Generation of 8‐epi‐prostaglandin F_2α in isolated rat kidney glomeruli by a radical‐independent mechanism

Cited by 29 publications

References 34 publications

Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression

Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression

Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity

Inhibition of Nitric Oxide Synthase Aggravates Cisplatin-Induced Nephrotoxicity: Effect of 2-Amino-4-Methylpyridine

Contact Info

Product

Resources

About

Generation of 8‐epi‐prostaglandin F2α in isolated rat kidney glomeruli by a radical‐independent mechanism

Cited by 29 publications

References 34 publications

Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression

Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression

Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity

Inhibition of Nitric Oxide Synthase Aggravates Cisplatin-Induced Nephrotoxicity: Effect of 2-Amino-4-Methylpyridine

Contact Info

Product

Resources

About

Generation of 8‐epi‐prostaglandin F_2α in isolated rat kidney glomeruli by a radical‐independent mechanism