Fetal Val108/158Met catechol-O-methyltransferase (COMT) polymorphism and placental COMT activity are associated with the development of preeclampsia.

Objective: To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels.

Design: Prospective case-control study.

Setting: University hospital.

2-methoxyestradiol plasma levels are associated with clinical severity indices and biomarkers of preeclampsia.

We investigated whether clinical severity indices and biomarkers for preeclampsia (PE) are associated with low plasmatic 2-methoxyestradiol (2ME) in the third trimester of gestation. Blood was collected from 53 women with PE and 73 control pregnant women before parturition. The concentration of 2ME was significantly higher in controls than in patients with PE (2906.

Reactive oxygen and nitrogen species in the renal ischemia/reperfusion injury.

Renal ischemia is the most common cause of acute kidney injury (AKI) still associated with high mortality rates of about 50% in the intensive care unit. Postischemic AKI is characterized by decreased glomerular filtration rate and high renal vascular resistance with endothelial activation and dysfunction, a process of critical importance that is followed by a reduction in microvascular blood flow mainly affecting the renal outer medulla. The pathophysiology of postischemic AKI remains incompletely understood, although it seems to be a phenomenon of altered renal hemodynamics, linked critically to the production of high amounts of nitric oxide and free radicals.

Sexual dimorphism in renal heme-heme oxygenase system in the streptozotocin diabetic rats.

Heme Oxygenase (HO) -1 and -2 exert antioxidant, cytoprotective and vascular actions in male diabetic rats. However, there is no information about the expression and functional significance of the renal HO system in diabetic females. The present study tested the hypothesis that the HO system is differentially regulated in the kidney of female Sprague Dawley diabetic rats, protecting it from nitrosative and glomerular functional damage.

Chronic tempol treatment attenuates the renal hemodynamic effects induced by a heme oxygenase inhibitor in streptozotocin diabetic rats.

Heme oxygenase-1 (HO-1) is induced by oxidative stress and plays an important role in protecting the kidney from oxidant-mediated damage in the streptozotocin (STZ) rat model of type-1 diabetes mellitus (DM-1). HO-derived metabolites, presumably carbon monoxide (CO), mediate vasodilatory influences in the renal circulation, particularly in conditions linked to elevated HO-1 protein expression or diminished nitric oxide (NO) levels. We tested the hypothesis that diabetes increases oxidative stress and induces HO-1 protein expression, which contributes to regulate renal hemodynamics in conditions of low NO bioavailability.

Sex differences in nitrosative stress during renal ischemia.

Females suffer a less severe ischemic acute renal failure than males, apparently because of higher nitric oxide (NO) bioavailability and/or lower levels of oxidative stress. Because the renal ischemic injury is associated with outer medullary (OM) endothelial dysfunction, the present study evaluated sex differences in OM changes of NO and peroxynitrite levels (by differential pulse voltammetry and amperometry, respectively) during 45 min of ischemia and 60 min of reperfusion in anesthetized Sprague-Dawley rats. Endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) protein expression and their phosphorylated forms [peNOS(Ser1177) and pnNOS(Ser1417)], 3-nitrotyrosine, reduced sulfhydryl groups (-SH), and glomerular filtration rate (GFR) were also determined.

Acute effects of 2-methoxyestradiol on endothelial aortic No release in male and ovariectomized female rats.

The endogenous metabolites of 17beta-estradiol are thought to have protective vascular effects, especially in males and estrogen-deprived females. The present study evaluated the acute in vitro effects of the active metabolite 2-methoxyestradiol on endothelial NO release from ovariectomized female and intact male and female rat aortas. NO was measured electrochemically by differential normal pulse amperometry using carbon fiber microsensors, and also by fluorescence microscopy using 4,5-diaminofluorescein diacetate.

Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury.

This study examined the effect of transfer of overlapping regions of chromosome 5 that includes (4A(+)) or excludes (4A(-)) the cytochrome P-450 4A (CYP4A) genes from the Lewis rat on the renal production of 20-hydroxyeicosatetraenoic acid (20-HETE) and the development of hypertension-induced renal disease in congenic strains of Dahl salt-sensitive (Dahl S) rats. The production of 20-HETE was higher in the outer medulla of 4A(+) than in Dahl S or 4A(-) rats. Mean arterial pressure (MAP) rose to 190 +/- 7 and 185 +/- 3 mmHg in Dahl S and 4A(-) rats fed a high-salt (HS) diet for 21 days but only to 150 +/- 5 mmHg in the 4A(+) strain.

Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite.

The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (-SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.

Renal ischemia induces an increase in nitric oxide levels from tissue stores.

Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect that has been shown to be partially independent from NO synthases. Because NO is stored in tissues as S-nitrosothiols and because these compounds could release NO during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an intracellular glutathione depletor), light stimulation (which releases NO, decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor that repletes S-nitrosothiols stores) on the changes in outer medullary NO concentration produced during 45 min of renal artery occlusion in anesthetized rats. Renal ischemia increased renal tissue NO concentration (+223%), and this effect was maintained along 45 min of renal arterial blockade.

Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin.

Background: Heme oxygenase (HO) products have a protective role in acute renal failure (ARF) that may be hemodynamically mediated because the HO-derived carbon monoxide (CO) is an important control system of arteriolar tone. The vascular effects of HO may be caused directly through changes in CO synthesis, and indirectly by alterations in nitric oxide (NO) release. The present study evaluated in vivo the renal effects of a heme oxygenase inhibitor, Co(III)Protoporphyrin (CoPP) alone or in combination with the CO donor dimanganese decacarbonyl (Mn2(CO)10).

Role of superoxide in modulating the renal effects of angiotensin II.

Angiotensin II is known to stimulate NADPH oxidase-dependent superoxide (O2-) generation, which may contribute to the acute renal vasoconstrictor and antinatriuretic actions of this peptide. To evaluate this hypothesis, the effects of a superoxide dismutase mimetic (tempol) or a NADPH inhibitor (apocynin) on the angiotensin renal actions were studied. Renal cortical nitric oxide (NO) was measured electrochemically in vivo.