NO Pathway (no + pathway)

Distribution by Scientific Domains

Selected Abstracts

Ascaris lumbricoides infection is associated with protection from cerebral malaria

Mathieu Nacher
Following reports of increased IgE in severe malaria and hypothesizing that helminth coinfections could modify its outcome, we conducted a retrospective case,control study to establish whether helminths affect the evolution of Plasmodium falciparum malaria. Some 182 severe cases, 315 mild controls and 40 controls with circulating schizonts were examined for intestinal helminths. Comparing cerebral malaria with mild controls, Ascaris lumbricoides was associated with a protective adjusted odds ratio (OR) of 0.58 (0.32,1.03) P = 0.06, for coinfection with Ascaris and Necator americanus, OR = 0.39 (0.17,0.88) P = 0.02. Protection followed a dose,effect trend (P = 0.008). When comparing cerebral malaria cases and controls with circulating schizonts the OR was 0.25 (0.009,0.67) P = 0.006. We hypothesized that Ascaris infected patients may have had decreased cyto-adherence, possibly through endothelial cell receptor downregulation and/or decreased splenic clearance leading to the absence of selection of virulent P. falciparum strains. IgE-anti-IgE immune complexes resulting from helminth preinfection may have an important role in influencing clinical presentation of severe malaria, and in establishing malaria tolerance, through the CD23/NO pathway. [source]

Inducible nitric oxide synthase expression in laryngeal neoplasia: Correlation with angiogenesis

Alessandro Franchi MD
Abstract Background The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma. Methods We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs. Results There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p = .04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p = .02) and in the group of SCCs (p = .01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p = .1) and was significantly associated with increased vascularization (p = .03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p = .02) and increased tumor vascularization correlated with higher cGMP levels (rs = .4; p = .01). Conclusions Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC. 2002 John Wiley & Sons, Inc. Head Neck 24: 16,23, 2002. [source]

Melatonin interactions with blood pressure and vascular function during l -NAME-induced hypertension

Ludovit Paulis
Abstract:, The mechanisms responsible for the antihypertensive effect of melatonin are not completely understood. To elucidate the possible role of the nitric oxide (NO) pathway in the hemodynamic actions of melatonin, the effects of this indolamine on vascular function during hypertension induced by the NO-synthase (NOS) inhibitor, N, -nitro- l -arginine-methyl ester (l -NAME) were investigated. Four groups of male adult Wistar rats were employed: control, L-NAME (40 mg/kg), melatonin (10 mg/kg) and l -NAME + melatonin for 5 wks. Systolic and diastolic blood pressure were measured invasively in the carotid artery. Conjugated dienes concentration (an oxidative load marker), NOS RNA expression and its activity and RNA expression of cyclooxygenase-(COX)-1 and COX-2 were determined in the aorta. Acetylcholine-induced responses and their NO-mediated component were evaluated in femoral and mesenteric artery. Moreover, endothelium-derived constricting factor (EDCF)-dependent vasoconstriction and inner diameter were determined in the femoral artery. Chronic l -NAME treatment induced hypertension, elevated the oxidative load and inhibited NOS activity. Moreover, impaired NO-dependent relaxation, augmented EDCF-constriction, increased COX-2 expression and reduced arterial inner diameter were observed. Melatonin added to l -NAME treatment completely prevented elevation of the oxidative load in the aorta. However, melatonin was not able to prevent NOS activity decline, elevation of COX-2 expression or the impairment of vascular responses (except moderate improvement in relaxation of small mesenteric arteries) and it exerted only slight antihypertensive effect. In conclusion, in addition to the reduction of the oxidative load, the restoration of the NO pathway seems to play an important role in the antihypertensive effect of melatonin. [source]

Endothelium-derived hyperpolarizing factor as an in vivo back-up mechanism in the cutaneous microcirculation in old mice

Marie Line Gaubert
There is now strong evidence that an endothelium-derived hyperpolarizing factor (EDHF), other than nitric oxide (NO) or prostaglandin (PG), exists for dilating arteries and arterioles. In vitro studies on isolated vessels pointed out a role for EDHF as a back-up mechanism when the NO pathway is impaired, but there was a lack of in vivo studies showing a functional role for EDHF. Ageing has pronounced effects on vascular function and particularly on endothelium-dependent relaxation, providing a novel situation in which to assess the contributions of EDHF. The purpose of the present study was thus to determine if, in vivo, there was a functional role for EDHF as a back-up mechanism in the cutaneous microcirculation in the ageing process. We investigated in vivo the contribution of each endothelial factor (NO, PG and EDHF) in the cutaneous vasodilatation induced by iontophoretic delivery of acetylcholine and local pressure application in young adult (6,7 months) and old (22,25 months) mice, using pharmacological inhibitors. The cutaneous vasodilator responses induced by acetylcholine and local pressure application were dependent upon NO and PG pathways in young adult mice, whereas they were EDHF-dependent in old mice. EDHF appears to serve as a back-up mechanism when ageing reaches pathological states in terms of the ability for NO and PG to relax cutaneous microvessels, allowing for persistent cutaneous vasodilatator responses in old mice. However, as a back-up mechanism, EDHF did not completely restore cutaneous vasodilatation, since endothelial responses were reduced in old mice compared to young adult mice. [source]

The Effect of Korean Red Ginseng Extract on the Relaxation Response in Isolated Rabbit Vaginal Tissue and Its Mechanism

Sun-Ouck Kim MD
ABSTRACT Introduction., Ginseng is an herbal medicine with a variety of biological activities. Aim., The purpose of this study was to investigate the effect of Korean red ginseng (KRG) extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism as a potential therapeutic agent for female sexual dysfunction. Method., Strips of rabbit vagina were mounted in organ chambers to measure isometric tension. After the strips were precontracted with phenylephrine, the contractile responses to KRG extract (1,20 mg/mL), nitric oxide inhibitor (N[omega]-nitro-L-arginine methyl ester [L-NAME]), an inhibitor of soluble guanylate cyclase (methylene blue), an inhibitor of Ca2+ -activated K+ channels (tetraethylammonium [TEA]), and an adenosine triphosphate (ATP)-sensitive K+ channel blocker (glybenclamide) were examined. Main Outcome Measures., The relaxation of the vaginal tissue strip was assessed after treating KRG extract or other chemicals. Results., KRG (1,20 mg/mL) extract relaxed the vaginal tissue strip in a dose-dependent manner up to 85%. The relaxation effect was significantly inhibited by L-NAME (30 M) and methylene blue (30 M) (P < 0.05). In addition, KRG inhibited the contraction induced by depolarization with 10, 20, and 40 mM KCl. The KRG-induced relaxation effect was significantly inhibited by TEA (300 M) (P < 0.05), and not by glybenclamide (30 M). Conclusions., These data show that KRG extract has a relaxing effect on rabbit vaginal smooth muscle tissue. These effects might be mediated partly through the NO pathway and hyperpolarization via Ca2+ -activated K+ channels. Kim S-O, Kim MK, Lee H-S, Park JK, and Park K. The effect of Korean red ginseng extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism. J Sex Med 2008;5:2079,2084. [source]

Nitric oxide and vascular insulin resistance

BIOFACTORS, Issue 1 2009
Guoyao Wu
Abstract Obesity and type-II diabetes are growing major health issues worldwide. They are the leading risk factors for vascular insulin resistance, which plays an important role in the pathogenesis of cardiovascular disease, the leading cause of death in developed nations. Recent studies have shown that reduced synthesis of nitric oxide (NO; a major vasodilator) from L -arginine in endothelial cells is a major factor contributing to the impaired action of insulin in the vasculature of obese and diabetic subjects. The decreased NO generation results from a deficiency of (6R)-5,6,7,8-tetrahydrobiopterin [BH4; an essential cofactor for NO synthase (NOS)], as well as increased generation of glucosamine (an inhibitor of the pentose cycle for the production of NADPH, another cofactor for NOS) from glucose and L -glutamine. Accordingly, endothelial dysfunction can be prevented by (1) enhancement of BH4 synthesis through supplementation of its precursor (sepiapterin) via the salvage pathway; (2) transfer of the gene for GTP cyclohydrolase-I (the first and key regulatory enzyme for de novo synthesis of BH4); or (3) dietary supplementation of L -arginine (which stimulates GTP cyclohydrolase-I expression and inhibits hexosamine production). Modulation of the arginine,NO pathway by BH4 and arginine is beneficial for ameliorating vascular insulin resistance in obesity and diabetes. 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]

Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome

HH Clarice Yang
Background and purpose:, During development of thoracic aortic aneurysms in a mouse model of Marfan syndrome, upregulation of matrix metalloproteinase (MMP)-2 and -9 was accompanied by compromised aortic constriction and endothelium-dependent relaxation. Losartan has been proposed for the prevention of thoracic aortic aneurysm. We hypothesized that losartan would suppress MMP-2/-9 activation and improve aortic vasomotor function in this model. Experimental approach:, A well-characterized mouse model of Marfan syndrome (Fbn1C1039G/+) was used. Starting at 6 weeks old, Marfan mice were untreated or given losartan (0.6 gL,1 in drinking water, n= 30). The littermate Fbn1+/+ mice served as control. Thoracic aortas were studied at 3, 6 and 9 months by histology and by contractility assays in isolated segments in vitro. Key results:, Losartan improved elastic fibre organization and increased aortic breaking stress. Losartan reduced the activity and protein expression of MMP-2 and MMP-9 at all ages. Aortic constriction in response to membrane depolarization or phenylephrine was increased by losartan at 3 and 9 months by 100,200%. Active force of aortic smooth muscle was also increased at 6 and 9 months. Acetylcholine-induced endothelium-dependent relaxation was improved by 30% after 3 months of losartan treatment, but such improvement disappeared with longer duration of treatment, accompanied by reduced phosphorylation of endothelial nitric oxide (NO) synthaseSer1177, AktThr308 and AktSer473, compared with the control. Conclusions and implications:, Losartan improved the contractile function of aorta and reduced MMP activation. However, the endothelial NO pathway remained suppressed in the thoracic aorta during losartan treatment, which might limit its long-term benefits in Marfan syndrome. [source]

Effects of oral L -arginine supplementation on blood pressure and asymmetric dimethylarginine in stress-induced preeclamptic rats

Zekiye Sultan Altun
Abstract This study was carried out to elucidate the role of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) in preeclampsia development, and to investigate the effect of L -arginine supplementation in rats. Preeclampsia was induced in pregnant rats using a stress model. L -arginine was administered orally and ADMA, urinary nitrate, and protein levels were measured on the 20th day of pregnancy. Compared with the group of rats that are normally pregnant, the levels of blood pressure (BP), protein excretion, and ADMA were significantly increased in preeclampsia which returned to normal levels following the supplementation of L -arginine. Both group of rats had similar urine nitrate levels. Arginine,ADMA,NO pathway is affected in preeclampsia. L -arginine supplementation decreased hypertension (HT), proteinuria, and ADMA levels indicating that taking L -arginine may be beneficial in preeclampsia treatment. Copyright 2008 John Wiley & Sons, Ltd. [source]


Lei Dang
SUMMARY 1.,Endothelial barrier dysfunction plays a pivotal role in the pathogenesis of diabetic vascular complications. The precise molecular mechanisms by which hyperglycaemia causes the increased permeability in endothelial cells are not yet well understood. In the present study, we investigated whether high concentrations of glucose induce endothelial permeability through the activation of protein kinase C (PKC) and/or the calcium,nitric oxide (NO) signalling pathway in human umbilical vein endothelial cells (HUVEC). 2.,Endothelial permeability was measured by albumin diffusion across endothelial monolayers under the stimuli of high glucose (HG; 20 mmol/L), 100 nmol/L phorbol-myristate-acetate (PMA) or 100 nmol/L histamine. The intracellular calcium concentration ([Ca2+]i) was detected in HUVEC using the fluorescent probe fura-2 AM. The effects of PKC inhibitors (LY379196 and hypocrellin A) and the NO synthase (NOS) inhibitor NG -monomethyl- l -arginine (l -NMMA) on endothelial permeability and [Ca2+]i were determined. 3.,High glucose and PMA increased endothelial permeability associated with decreased [Ca2+]i, whereas histamine triggered significant increases in endothelial permeability, accompanied by increases in [Ca2+]i in HUVEC. Hypocrellin A (HA) and LY379196 reversed both HG- and histamine-induced endothelial permeability. The NOS inhibitor l -NMMA only abolished histamine- and not HG-induced endothelial permeability. Neither LY379196, HA nor l -NMMA had any significant effects on alterations in [Ca2+]i caused by HG and histamine. 4.,These results indicate that increased endothelial permeability in HUVEC induced by HG is dependent on PKC activity and is independent of the [Ca2+]i,NO pathway. Increased endothelial permeability due to other inflammatory factors, such as histamine, may also be mediated by the PKC pathway. Thus, PKC inhibitors would be a potential therapeutic approach to endothelial dysfunction induced by hyperglycaemia, as well as other inflammatory factors, in diabetes. [source]

ORIGINAL RESEARCH,BASIC SCIENCE: Enhancement of Both EDHF and NO/cGMP Pathways Is Necessary to Reverse Erectile Dysfunction in Diabetic Rats

Javier Angulo PhD
ABSTRACT Aims and Methods., Phosphodiesterase 5 (PDE5) inhibitors are less effective in the treatment of erectile dysfunction (ED) in diabetic men than in nondiabetic patients. We have evaluated the effects of sildenafil, a PDE5 inhibitor that enhances the nitric oxide (NO)/cGMP pathway, calcium dobesilate (DOBE), which potentiates endothelium-derived hyperpolarizing factor (EDHF)-mediated responses and the combination of both on erectile responses elicited by cavernosal nerve electrical stimulation (CNES) in a rat model of ED after 8 weeks of streptozotocin-induced diabetes. Results., After 8 weeks of diabetes, erectile responses to CNES were significantly decreased in diabetic animals compared with nondiabetic time controls. While intravenous administration of sildenafil (0.3 mg/kg) or DOBE (10 mg/kg), individually, enhanced erectile responses in nondiabetic rats (214.7 34.1% and 268.5 30.1% of control response at 1 Hz, respectively), each failed to significantly enhance erectile responses in diabetic rats. Only when administered in combination did DOBE and sildenafil markedly potentiate erectile responses in these animals (380.1 88.6% of control response at 1 Hz), completely restoring erectile function. Conclusions., These findings emphasize the importance of NO/cGMP and EDHF pathways for normal erectile function. They also give support to the in vitro observation that diabetes impairs NO and EDHF-dependent responses, precluding the complete recovery of erectile function with PDE5 inhibitors and explaining the relatively poor clinical response of diabetic men with ED to PDE5 inhibition. Finally, our study suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men. [source]