This study investigated whether endothelin-1 (ET-1), a potent vasoconstrictor, which also stimulates cell proliferation, contributes to endothelial dysfunction and atherosclerosis. Apolipoprotein E (apoE)-deficient mice C57BL/6 control were treated with Western-type diet accelerate atherosclerosis or without ET A receptor antagonist LU135252 (50 mg/kg/d) for 30 wk. Systolic blood pressure, plasma lipid profile, nitrate levels determined. In the aorta, NO-mediated endothelium-dependent...

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto were used. cNOS stimulated by calcium ionophore A23187. In situ measurements hydrogen peroxide electrochemical sensors production chemiluminescence...

In vitro studies on vascular smooth muscle cells suggest that endothelin has a stimulating effect cellular proliferation. This study was designed to determine the endogenous of angiotensin II-induced hypertrophy small arteries in vivo.Two weeks II administration (200 ng x kg[-1] min[-1]) increased media thickness, media/lumen ratio, and cross-sectional area basilar mesenteric arteries, confirming proliferative properties II. The tissue levels endothelin-1 were elevated after administration....

In cultured endothelial cells, the antioxidant, L-ascorbic acid (vitamin C), increases nitric oxide synthase (NOS) enzyme activity via chemical stabilization of tetrahydrobiopterin. Our objective was to determine effect vitamin C on NOS function and tetrahydrobiopterin metabolism in vivo. Twenty-six twenty-eight weeks diet supplementation with (1%/kg chow) significantly increased circulating levels wild-type (C57BL/6J) apolipoprotein E (apoE)--deficient mice. Measurements enzymatic aortas...

Sodium plays an important role in the pathogenesis and therapy of hypertension, a major risk factor for cardiovascular disease. This study investigated involvement endothelin vascular alterations salt-induced Dahl hypertension. Salt-sensitive (DS) salt-resistant (DR) rats were treated with high-sodium diet (NaCl 4%) or without ET A receptor antagonist LU135252 two months, effects treatments on systolic blood pressure, endothelin-1 (ET-1) protein content, aortic hypertrophy, reactivity...

Abstract —Endothelium-dependent relaxations mediated by NO are impaired in a mouse model of human atherosclerosis. Our objective was to characterize the mechanisms underlying endothelial dysfunction aortas apolipoprotein E (apoE)-deficient mice, treated for 26 29 weeks with lipid-rich Western-type diet. Aortic rings from apoE-deficient mice showed endothelium-dependent acetylcholine (10 − 9 10 5 mol/L) and Ca 2+ ionophore 6 endothelium-independent diethylammonium ( Z )-1-( N ,...

Angiotensin II, a constrictor and mitogen of vascular smooth muscle cells, affects the release endothelium-derived factors such as nitric oxide or endothelin-1. This study investigated influence endothelin-1, using selective endothelin A receptor antagonist LU135252 , on blood pressure endothelial function in angiotensin II-induced hypertension rat. Two weeks II administration (200 ng/kg per minute) increased systolic (+35±5 mm Hg; tail-cuff method) compared with placebo ( P <.05). alone...

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration function in nonhematopoietic tissues. However, the minimum effective dose required to mimic augment these normal paracrine functions (EPO) some organs (e.g., brain) higher than treatment anemia. Notably, dose-dependent risk adverse effects has been associated with rhEPO administration, especially high-risk groups, including polycythemia–hyperviscosity...

The role of prostaglandin production in the control regenerative function endothelial progenitor cells (EPCs) has not been studied. We hypothesized that activation cyclooxygenase (COX) enzymatic activity and subsequent prostacyclin (PGI(2)) is an important mechanism responsible for EPCs. In present study, we detected high levels COX-1 protein expression PGI(2) biosynthesis human EPCs outgrown from blood mononuclear cells. Expression COX-2 was almost undetectable under basal conditions but...

The exact mechanism of angiogenesis by europium hydroxide nanorods was unclear. In this study we have showed that formation reactive oxygen species (H2O2 and O2·−) is involved in redox signaling pathways during angiogenesis, important for cardiovascular ischemic diseases. Here used single-walled carbon nanotube sensor array to measure the single-molecule efflux H2O2 a HPLC method determination O2·– from endothelial cells response proangiogenic factors. Additionally, species-mediated using...

Abstract The involvement of endothelin in salt-induced hypertension is unclear. In the Dahl rat model, we studied effects a selective endothelin-subtype A (ET ) receptor antagonist, LU135252 , on blood pressure, vascular structure, and function. salt-sensitive salt-resistant rats were treated for 8 weeks with 4% NaCl alone or combination taken orally (60 mg/kg per day). geometry reactivity basilar mesenteric arteries vitro under perfused pressurized conditions using video dimension analyzer....

Abstract —In the C57BL/6J mice model, we investigated whether obesity affects function or expression of components tissue renin-angiotensin system and endothelin (ET)-1 contributes to these changes. ACE activity (nmol · L His-Leu mg protein −1 ) was measured in lung, kidney, liver control (receiving standard chow) obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone combination LU135252 , an orally active ET A receptor antagonist. mRNA effects on purified human were...

Erythropoietin (EPO) fosters tissue oxygenation by stimulating erythropoiesis. More recently, EPO has been recognized as a tissue-protective cytokine. In this study, we tested the hypothesis that endothelial NO synthase (eNOS) plays key role in vascular protective effect of EPO. A murine model wire-induced injury carotid artery was used to examine on repair and arterial wall architecture. Recombinant human (1000 U/kg, SC, biweekly) administered for 2 weeks wild-type eNOS-deficient mice after...

Shear stress, imposed on the vascular endothelium by circulating blood, critically sustains synthesis of nitric oxide (NO). Endothelial NO synthase (eNOS) activity is determined heat shock protein 90 (HSP90), caveolin-1, and cofactor tetrahydrobiopterin (BH4). To determine whether increased blood flow concomitantly upregulates eNOS GTP cyclohydrolase I (GTPCH I, rate-limiting enzyme in BH4 biosynthesis), an aortocaval fistula model rat was employed wherein aortic enhanced proximal but...

Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is tightly regulated by its accessory β(1) subunit (BK-β(1)). Downregulation BK-β(1) expression in diabetic vessels associated with upregulation forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box-only protein (FBXO) expression. However, upstream signaling regulating this process unclear. Overproduction reactive oxygen species (ROS) a common finding vasculopathy. We hypothesized that ROS...

In this study, we used the GTP cyclohydrolase I-deficient mice, i.e., hyperphenylalaninemic (hph-1) to test hypothesis that loss of tetrahydrobiopterin (BH(4)) in cerebral microvessels causes endothelial nitric oxide synthase (eNOS) uncoupling, resulting increased superoxide anion production and inhibition signaling. Both homozygous mutant (hph-1(-/-)) heterozygous (hph-1(+/-) mice) demonstrated reduction I activity reduced bioavailability BH(4). hph-1(+/-) hph-1(-/-) was inhibited by...

Phosphorylation of eNOS, an important post-translational modulator its enzymatic activity, is reduced in diabetes mellitus. We hypothesized that modulation eNOS phosphorylation could overcome diabetic vascular dysfunction and improves the outcome to stroke.We used db/db mouse model type 2 mated mice with knock-in carry single amino acid mutations at S1176 site; phosphomimetic SD mutation (serine replaced by aspartate) shows increased whereas unphosphorylatable SA alanine) decreased activity....

Abstract. This study investigated the role of renal nitric oxide synthase (NOS), endothelin, and possible mechanisms renovascular dysfunction in salt-sensitive hypertension. Salt-sensitive (DS) salt-resistant (DR) Dahl rats were treated for 8 wk with high salt diet (4% NaCl) alone or combination ET A receptor antagonist LU135252 (60 mg/kg per d). Salt loading markedly increased NOS activity (pmol citrulline/mg protein min) cortex medulla DR but not DS by 270 246%, respectively. Hypertension...

Abstract —Endothelin partially mediates angiotensin (Ang) II–induced vascular changes in vivo. This study investigated the effects of type 1 receptor antagonist losartan and calcium channel blocker verapamil on reactivity tissue endothelin-1 levels aortas Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng · kg −1 min ). increased systolic blood pressure (39±4 mm Hg, P <0.05). Concomitant treatment abolished increase ( <0.05), whereas reduced it only In hypertension, content was...

The effects of Western-type fat diet on endothelium-dependent relaxations and vascular structure in carotid arteries from a mouse model human atherosclerosis are not known. Our objective was to characterize the mechanisms underlying endothelial dysfunction apoE-deficient mice.C57BL/6J mice were fed for 26 weeks with lipid-rich diet. Changes intraluminal diameter pressurized common (ID 450 micrometer) measured vitro video dimension analyzer. Endothelial NO synthase protein content evaluated...

ANG II induces vasoconstriction, at least in part, by stimulating NADPH oxidase and generating reactive oxygen species. also heme oxygenase activity, bilirubin, a product of such possesses antioxidant properties. We hypothesized that because its properties, may reduce the pressor prooxidant effects II. Our vivo studies used hyperbilirubinemic Gunn rat which is deficient enzyme uridine diphosphate glucuronosyl transferase, latter enabling excretion bilirubin into bile. (0.5 mg x kg(-1)...