Disruption of endothelial peroxisome proliferator-activated receptor-gamma reduces vascular nitric oxide production.

Vascular endothelial cells express the ligand-activated transcription factor, peroxisome proliferator-activated receptor-gamma (PPARgamma), which participates in the regulation of metabolism, cell proliferation, and inflammation. PPARgamma ligands attenuate, whereas the loss of function mutations in PPARgamma stimulate, endothelial dysfunction, suggesting that PPARgamma may regulate vascular endothelial nitric oxide production. To explore the role of endothelial PPARgamma in the regulation of vascular nitric oxide production in vivo, mice expressing Cre recombinase driven by an endothelial-specific promoter were crossed with mice carrying a floxed PPARgamma gene to produce endothelial PPARgamma null mice (ePPARgamma(-/-)).

Rosiglitazone attenuates chronic hypoxia-induced pulmonary hypertension in a mouse model.

Chronic hypoxia contributes to pulmonary hypertension through complex mechanisms that include enhanced NADPH oxidase expression and reactive oxygen species (ROS) generation in the lung. Stimulation of peroxisome proliferator-activated receptor gamma (PPARgamma) reduces the expression and activity of NADPH oxidase. Therefore, we hypothesized that activating PPARgamma with rosiglitazone would attenuate chronic hypoxia-induced pulmonary hypertension, in part, through suppressing NADPH oxidase-derived ROS that stimulate proliferative signaling pathways.

Long-term exposure to AZT, but not d4T, increases endothelial cell oxidative stress and mitochondrial dysfunction.

Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT) and stavudine (d4T), cause toxicities to numerous tissues, including the liver and vasculature. While much is known about hepatic NRTI toxicity, the mechanism of toxicity in endothelial cells is incompletely understood. Human aortic endothelial and HepG2 liver cells were exposed to 1 muM AZT or d4T for up to 5 weeks.

The role of NADPH oxidase in chronic intermittent hypoxia-induced pulmonary hypertension in mice.

Obstructive sleep apnea, characterized by intermittent periods of hypoxemia, is an independent risk factor for the development of pulmonary hypertension. However, the exact mechanisms of this disorder remain to be defined. Enhanced NADPH oxidase expression and superoxide (O2(-).

Vascular oxidative stress and nitric oxide depletion in HIV-1 transgenic rats are reversed by glutathione restoration.

Human immunodeficiency virus (HIV)-infected patients have a higher incidence of oxidative stress, endothelial dysfunction, and cardiovascular disease than uninfected individuals. Recent reports have demonstrated that viral proteins upregulate reactive oxygen species, which may contribute to elevated cardiovascular risk in HIV-1 patients. In this study we employed an HIV-1 transgenic rat model to investigate the physiological effects of viral protein expression on the vasculature.

Attenuation of signaling and nitric oxide production following prolonged leptin exposure in human aortic endothelial cells.

Acute leptin exposure stimulates endothelial nitric oxide (NO) production in vitro. In contrast, chronic elevations in circulating leptin levels in patients with obesity are associated with endothelial dysfunction and impaired endothelial NO production. Therefore, the goal of the current study was to examine the direct effects of acute and more sustained leptin stimulation on endothelial nitric oxide synthase (eNOS) and NO production in human aortic endothelial cells (HAECs).

Chronic ethanol ingestion increases aortic endothelial nitric oxide synthase expression and nitric oxide production in the rat.

Background: Chronic alcohol consumption perturbs cellular function in a variety of organ systems. Previous studies have suggested that moderate alcohol consumption reduces vascular disease, whereas heavier alcohol consumption may worsen it. The mechanisms for these vascular effects of chronic alcohol ingestion continue to be defined and constitute the focus of this study.

The PPARgamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice.

Oxidative stress plays an important role in diabetic vascular dysfunction. The sources and regulation of reactive oxygen species production in diabetic vasculature continue to be defined. Because peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reduced superoxide anion (O(2)(-.

The measurement of nitric oxide production by cultured endothelial cells.

Nitric oxide (NO) produced by vascular endothelial cells (ECs) plays a critical role in normal vascular physiology. Important insights into mechanisms regulating the production of endothelial NO have been derived from in vitro studies employing cultured ECs. Although many techniques for the detection of NO have been described, many of these methods lack adequate sensitivity to detect the small amount of NO produced by cultured ECs.

Hepatic insulin gene therapy prevents deterioration of vascular function and improves adipocytokine profile in STZ-diabetic rats.

Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in diabetic rodents, suggesting that similar approaches may eventually provide a means to improve treatment of diabetes mellitus. However, whether the metabolic and hormonal changes produced by HIGT benefit vascular function remains unclear. The impact of HIGT on endothelium-dependent vasodilation, nitrosyl-hemoglobin content (NO-Hb), and insulin sensitivity were studied using aortic ring preparations, electron spin resonance spectroscopy (ESR), homeostasis assessment of insulin resistance (HOMA-IR) calculations, and insulin tolerance testing (ITT).

Role of SGK1 in nitric oxide inhibition of ENaC in Na+-transporting epithelia.

Several studies have shown that nitric oxide (NO) inhibits Na(+) transport in renal and alveolar monolayers. However, the mechanisms by which NO alters epithelial Na(+) channel (ENaC) activity is unclear. Therefore, we examined the effect of applying the NO donor drug l-propanamine 3,2-hydroxy-2-nitroso-1-propylhidrazino (PAPA-NONOate) to cultured renal epithelial cells.

Peroxisome proliferator-activated receptor-gamma ligands regulate endothelial membrane superoxide production.

Recently, we demonstrated that the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands, either 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) or ciglitazone, increased endothelial nitric oxide (.NO) release without altering endothelial nitric oxide synthase (eNOS) expression (4). However, the precise molecular mechanisms of PPAR-gamma-stimulated endothelial.

Fatty acids differentially modulate insulin-stimulated endothelial nitric oxide production by an Akt-independent pathway.

Background: Insulin increases endothelial nitric oxide (NO) production by activating endothelial nitric oxide synthase (eNOS) through protein kinase B (Akt)-mediated phosphorylation of serine residue 1179 (p-eNOS serine 1179). Because fatty acids modulate insulin-stimulated Akt signaling cascades in smooth muscle cells, we hypothesized that fatty acids would differentially regulate endothelial Akt signaling, eNOS phosphorylation, and NO production.

Methods: Porcine pulmonary artery endothelial cells (PAECs) were treated for 3 hours with 100 microM oleic (18:1) or eicosapentaenoic (20:5) acids or with an equivalent volume of ethanol vehicle (0.

Detection of endothelial nitric oxide release with the 2,3-diaminonapthalene assay.

The reliable measurement of nitric oxide (NO) production by endothelial cells in vitro has become an important tool for investigating mechanisms of endothelial dysfunction. This study evaluates measuring NO production by cultured porcine pulmonary artery endothelial cells (PAEC) using the assay based on the fluorometric detection of 1-(H)-naphthotriazole, the fluorescent product of the reaction between nitrite (NO2-) and 2,3-diaminonapthalene (DAN). To stimulate NO production, PAEC were treated for 60 min with agonists known to stimulate endothelial NO production.