Nitric oxide is a soluble gas continuously synthesized by the endothelium. Ox-LDL was significantly correlated with left atrium diameter(r=0.358, p=0.005) independently of other clinical variables (beta(SE):1.288(0.455), p=0.007). CCA injury in ApoE KO mice resulted in the formation of atheromatous lesions while C57 mice showed no change (intima 27,795 ± 1829 vs 237 ± 28 μm(2); media 46,306 ± 2448 vs 11,714 ± 392 μm(2), respectively; P < .001). These results suggest that gluteal subcutaneous small resistance arteries of male essential hypertensive patients exhibit a decrement in responsiveness to endothelin-1. The maximum diameter of left atrium is the only independent predictor of oxidized LDL, suggesting that left atrium distension may predict oxidative stress status in these patients. Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme nitric Therefore, metabolic abnormalities such as insulin resistance, dyslipidemia, compensatory hyperinsulinemia and overt hyperglycemia may all contribute to impaired NO bioavailability and abnormal vasodilatation in diabetic patients. NOS1 is the neural (or brain) isoform, also known as nNOS. The effects of series of alpha, beta-unsaturated aldehydes on hepatic glutathione, cytochrome P450, and NADPH-cytochrome c reductase activity were compared with time. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). However, only CC-genotype ECs responded to FSS with an Egr-1-mediated increase in manganese-containing superoxide dismutase (SOD-2) expression, shielding them from endothelin-1-induced oxidative stress in a NO-independent manner. Asymmetric dimethylarginine (ADMA) has evolved as an important regulator of nitric oxide (NO) synthesis in recent years. I.v. Both nitric oxide and prostacyclin inhibited monocyte chemotaxis stimulated by N-formyl-methionyl-leucyl-phenylalanine and induced dose-dependent increases in intracellular cyclic guanosine monophosphate and cyclic adenosine monophosphate concentrations, respectively. Taken together, our data suggest that the endothelial dysfunction observed in MCA associated with hypercholesterolemia is prevented by cilostazol, an effect likely due to the increase in eNOS phosphorylation and, therefore, activity. The health of your endothelial cells also plays a vital role in one other critical factor. Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Endothelial derived NO is often seen as a protective agent in a variety of diseases. OxLDL increased SMC proliferation by >50%. Benzoate monohydroxy compounds, and in particular salicylate, were produced during interaction of ferrous complexes with hydrogen peroxide (Fenton reaction) in a N2 environment. The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). This FSS-induced rise in SOD-2 expression in CC-genotype ECs effectively stabilizes their antiatherosclerotic phenotype and may explain not only the comparatively slow onset of CAD in homozygous carriers of the C-allele of the nos-3 gene but also define a general strategy for preventing endothelial dysfunction at the outset of atherosclerosis. NG-Monomethyl-L-arginine (L-MeArg), a selective inhibitor of nitric oxide (NO) synthesis from L-arginine, reduces this increase and enhances aggregation. Intracarotid (i.c.) Early hypercholesterolemia impairs endothelial function, with severity being related to duration and magnitude of hypercholesterolemia. This treatment also decreased the 2α, 2β, 6β, 16α, and 16β hydroxylation of testosterone as well as androstenedione formation showing effects on individual cytochrome P450 isozymes. Thrombospondin‐5 and fluvastatin promote angiogenesis and are protective against endothelial cell apoptosis, Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions, Associations between PHACTR1 gene polymorphisms and pulse pressure in Chinese Han population, Upregulation of eNOS and unchanged energy metabolism in increased susceptibility of the aging type 2 diabetic GK rat heart to ischemic injury, ADMA is a correlate of insulin resistance in early-stage diabetes independent of hs-CRP and body adiposity, Alterations in Nitric Oxide and Endothelin-1 Bioactivity Underlie Cerebrovascular Dysfunction in ApoE-Deficient Mice, HMG-CoA Reductase Inhibitor Improves Endothelial Dysfunction in Spontaneous Hypertensive Rats Via Down-regulation of Caveolin-1 and Activation of Endothelial Nitric Oxide Synthase, Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE(-/-) mice, Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction, Effect of Endothelium-Specific Insulin Resistance on Endothelial Function In Vivo, Creager M, Gallagher S, XJ G, Coleman S, Dzau V, Cooke JL-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. However, the underlying mechanisms regulating the expression of inflammatory markers or oxidative stress status are unclear. These results suggest that endogenous nitric oxide may function as a modulator of vascular smooth muscle cell mitogenesis and proliferation, by a cGMP-mediated mechanism. Next, flow was restored with 0.4 mM palmitate buffer for 32 min. The endothelial nitric oxide synthase (eNOS) generates the vasoprotective molecule nitric oxide (NO), which plays a central role in the control of vascular hemostasis. 4-18(15), DOI: https://doi.org/10.2174/157016112798829760, Keywords: Biochem Biophys Res Commun 181:1392-1397, Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine, Pharmacological Properties of the Tachykinin Receptor Subtype in the Endothelial Cell and Vasodilation, Isoforms of nitric oxide synthase Characterization and purification from different cell types, Nitric oxide and prostacyclin. Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina. Caveolin-1 regulates nitric oxide (NO) signaling by modulating endothelial nitric oxide synthase (eNOS). Animal models that show vascular dysfunction demonstrate the protective role of endothelial NO dependent pathways. This substance has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood, playing in this way a crucial role in the normal endothelial function. Furthermore, the vascular action of insulin was lost in ESMIRO mice, and insulin-induced endothelial NO synthase (eNOS) phosphorylation was blunted. Acrolein or muconaldehyde reduced glutathione to 51 and 75% of controls, respectively, at 4 hr; glutathione returned to control values at 24 hr. L-arginine and L-citrulline increased production of NO and prevented salt-sensitive hypertension in Dahl/Rapp rats. Normal coronary vessels had a biphasic response to intracoronary serotonin: dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4) mol per liter. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency. These findings support early correction of hypercholesterolemia and emphasize the potential role for NO based therapies in disease states. Studies were repeated after CCA injury. The endothelium is the inner lining of blood vessels, and it plays a critical role in regulating the flow of blood. Pitavastatin (0.1 and 0.3 mg x kg(-1)) was given orally once a day for 8 weeks. Humans with atherosclerosis, diabetes, or hypertension often show impaired NO pathways. Vascular responses were evaluated by quantitative angiography. The contribution of the leukocyte adhesion glycoprotein CD11/CD18 was determined using the CD18-specific monoclonal antibody IB4. This action must occur before the assembly of the activated complex. Nitric oxide significantly inhibited the generation of superoxide anion by neutrophils exposed to either FMLP (10(-7)M) or PMA (150 ng/ml) (IC50 = 30 microM). Nitric oxide is a potent vasodilator that improves vascular health and function through its antithrombotic, … These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions. Lumen diameters were significantly smaller in hypertensives and the media:lumen ratio was significantly increased in hypertensive patients. The relaxations induced by EDRF and NO were inhibited by haemoglobin and enhanced by superoxide dismutase to a similar degree. Modifications in the NO pathway may play a major role in ischemia-reperfusion injury of the type 2 diabetic GK rat heart. Endothelial nitric oxide (NO) possesses various antiatherosclerotic properties. NO and NO-producing vasodilators inhibited the DNA synthesis that was induced by 10% fetal calf serum. Eight-week-old male SHR were assigned to either a control group (CON, n=11) or a rosuvastatin group (ROS, n=12), rosuvastatin (10 mg/kg/day) administered for eight weeks. databases (up to January 31, 2014), including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), using an established strategy. Normotensive male subjects and sex- and age-matched mild essential hypertensive patients who had not received antihypertensive drugs for more than 6 months were investigated. NOx was increased during baseline conditions (P < 0.05) and after reperfusion (P < 0.05) in GK rat hearts. Statins, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, protect against deleterious effects of chronic nitric oxide inhibition. Since nitrite has been shown to be potently cytoprotective and restore NO biochemical homeostasis, we investigated if supplemental nitrite could attenuate microvascular inflammation caused by a high cholesterol diet. The results showed that metmyoglobin and oxymyoglobin were activated by H2O2 to ferryl myoglobin, which initiates membrane lipid peroxidation; but not nitric oxide-myoglobin, which, during interaction with H2O2, did not form ferryl but metmyoglobin which only poorly affected lipid peroxidation. In contrast, L-arginine did not alter the development of hypertension in spontaneously hypertensive rats. To eliminate the potential confounding effects of atherosclerosis, vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211 +/- 19 mg/dl, P less than 0.05). L-Arginine also inhibits platelet aggregation in whole blood in a similar manner, although the concentrations required are considerably higher. Therefore, strategies that increase endothelial NO production have potential utility. The other isoforms include neuronal nitric oxide synthase, which is … Nitric Oxide Toxicity Loss of nitric oxide function is one of the earliest indicators of disease. Age- and sex-adjusted ADMA values were significantly (p<0.05) correlated with hs-CRP (r=0.279) and HOMA-IR (r=0.288) in diabetic patients. In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). NO and ONOO(-) released from isolated aortae by calcium ionophore were measured with nanosensors placed 6 +/- 2 nm from aortic endothelium. While nitric oxide is essential for life, excessive amounts of nitric oxide can be deadly and actually contribute to heart disease and strokes, arthritis, asthma and Alzheimer's disease. Moreover, the inhibition of mitogenesis and proliferation was shown to be independent of cell damage, as documented by several criteria of cell viability. Using human aortic ECs and bovine aortic ECs, we show that AMPK activation upregulates ATP binding cassette G1 (ABCG1) expression independently of liver X receptor alpha (LXR alpha) transcriptional activity but through a posttranscriptional mechanism that increases mRNA stability. Infusion of L-NMMA acutely decreased, whereas intravenous L-arginine rapidly increased, urinary cGMP in both groups. Tetrahydrobiopterin (BH4) is an important cofactor for endothelial nitric oxide synthase activity. Pharmacologic approaches to reduce endothelin-1 system activation have produced limited results and are largely disease-specific. Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. This study examined the contribution of nitric oxide (NO) to the susceptibility or resistance to the hypertensive effects of high sodium chloride (8.0% NaCl) intake in young Dahl/Rapp salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats. In ST, prostacyclin metabolites and NO concentrations were not significantly increased and autoantibodies against ox-LDL concentrations did not change. Profiling of aortic smooth muscle cell gene expression in response to chronic inhibition of nitric oxide synthase in rats. Conclusions: The induction of PPARalpha mRNA expression by atorvastatin in L-NAME treated rats also suggests that this pathway could participate in the protective effect. Insulin resistance is an independent risk factor for the development of cardiovascular atherosclerosis. We report increased susceptibility of type 2 diabetic GK rat heart to ischemic injury that is not associated with impaired energy metabolism. The cell surface expression of the CD11b/CD18 adhesion receptor, a glycoprotein complex known to mediate monocyte intracellular adhesion, was not altered by either nitric oxide or by prostacyclin. A cGMP analog, 8-bromo-cGMP, inhibited DNA synthesis in the RACS-1 cells. Nitrovasodilators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott that EDRF may be NO. Endothelial NOS phosphorylation at Ser(1179) was decreased in the aorta of ApoE(-/-) mice compared with WT mice (P<0.05), an effect normalized by cilostazol. Diabetic patients were recently diagnosed and did not have a history of any diabetes-related complications. Common carotid arteries (CCA) from wild-type C57BL6 (WT or C57) and apolipoprotein E deficient (ApoE KO) mice fed normal or Western diets for 6 to 8 weeks were tested for vasomotor function using an arteriograph system. This review outlines the most important mechanisms by which insulin takes part in physiological regulation of endothelial function. 4. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Objective: Forearm blood flow was determined by venous occlusion plethysmography. Mass spectrometry studies using 15N-labelled L-arginine indicated that this enhancement was due to the formation of NO from the terminal guanidino nitrogen atom(s) of L-arginine. The consequent generation of NO modulates platelet reactivity by increasing cyclic GMP. But as we age, our body makes less nitric oxide. However, endothelin-1-mediated vasoconstrictor tone increases with age and contributes to the pathogenesis of hypertension. 2-4. nitric oxide; Insulin resistance is associated with endothelial dysfunction; however, the mechanistic relationship between these abnormalities and the role of impaired endothelial insulin signaling versus global insulin resistance remains unclear. 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