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Sodium Nitroprusside (sodium + nitroprusside)
Kinds of Sodium Nitroprusside Selected AbstractsVoltammetric Sensor for Sodium Nitroprusside Determination in Biological Fluids Using Films of Poly- L -LysineELECTROANALYSIS, Issue 9 2007Claudece Pereira, Francisco Abstract Sodium nitroprusside (NP), a commercial vasodilator, can be pre-concentrated on vitreous carbon electrode modified by films of 97.5%: 2.5% poly- L -lysine (PLL): glutaraldehyde (GA). This coating gives acceptable anion exchange properties whilst giving the required improvement of adhesion to the glassy carbon electrode surface. Linear response range and detection limit on nitroprusside in B-R buffer pH,4.0, were 1×10,6 to 2×10,5 mol L,1 and 1×10,7 mol L,1, respectively. The repeatability of the proposed sensor, evaluated in term of relative standard deviation, was measured as 4.1% for 10 experiments. The voltammetric sensor was directly applied to determination of nitroprusside in human plasma and urine samples and the average recovery for these samples was around 95,97% without any pre treatment. [source] Nuclear factor-kappaB as a molecular target for migraine therapy.HEADACHE, Issue 4 2003U Reuter Ann Neurol. 2002;51:507-516. Nitric oxide (NO) generated from inducible NO synthase (iNOS) participates in immune and inflammatory responses in many tissues. The NO donor glyceryl trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs and also causes iNOS expression and delayed inflammation within rodent dura mater. Sodium nitroprusside, an NO donor as well, also increases iNOS expression. Because inflammation and iNOS are potential therapeutic targets, we examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater. We show that intravenous GTN increases NO production within macrophages. L-N(6)-(1-iminoethyl)lysine, a selective iNOS inhibitor, attenuates the NO signal, emphasizing the importance of enzymatic activity to delayed NO production. iNOS expression is preceded by significant nuclear factor kappa B (NF-kappaB) activity, as reflected by a reduction in the inhibitory protein-kappa-Balpha (IkappaBalpha) and activation of NF-kappaB after GTN infusion. IkappaBalpha degradation, NF-kappaB activation, and iNOS expression were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an anti-inflammatory drug used for migraine treatment. These findings suggest that GTN promotes NF-kappaB activity and inflammation with a time course consistent with migraine attacks in susceptible individuals. We conclude, based on results with this animal model, that blockade of NF-kappaB activity provides a novel transcriptional target for the development of anti-migraine drugs. Comment: This paper suggesting the localization of NO production in dural macrophages as part of delayed inflammation may indicate proliferation and or recruitment of these cells in migraine. Could this also be a target for drug treatment? Specifically, is the genetic transcription that leads to nitric oxide generation such a target? To amend slightly the old advertising slogan, "when Michael Moskowitz talks, we all listen." DSM and SJT [source] Exogenously Applied Nitric Oxide Enhances the Drought Tolerance in Fine Grain Aromatic Rice (Oryza sativa L.)JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 4 2009M. Farooq Abstract Drought stress is a severe threat to the sustainable rice production, which causes oxidative damage and disturbs plant water relations, while exogenously applied nitric oxide (NO) may have the potential to alleviate these effects in rice plants. In this study, the role of NO to improve drought tolerance in fine grain aromatic rice (Oryza sativa L. cv. Basmati 2000) was evaluated. Sodium nitroprusside, a NO donor, was used at 50, 100 and 150 ,mol l,1 both as seed priming and foliar spray. To prime, the seeds were soaked in aerated NO solution of respective solution for 48 h and dried back to original weight. Primed and non-primed seeds were sown in plastic pots with normal irrigation in a greenhouse. At four leaf stage, plants were subjected to drought stress except the controls, which were kept at full field capacity. Drought was maintained at 50 % of field capacity by watering when needed. Two controls were maintained; both receiving no NO treatments as foliar application or seed treatment, one under drought conditions and the other under well-watered conditions. Drought stress seriously reduced the rice growth, but both methods of NO application alleviated the stress effects. Drought tolerance in rice was strongly related to the maintenance of tissue water potential and enhanced capacity of antioxidants, improved stability of cellular membranes and enhanced photosynthetic capacity, plausibly by signalling action of NO. Foliar treatments proved more effective than the seed treatments. Among NO treatment, 100 ,mol l,1 foliar spray was more effective. [source] Methylene blue inhibits angiogenesis in chick chorioallontic membrane through a nitric oxide-independent mechanismJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2006N. Zacharakis Abstract Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study was to evaluate the effect of methylene blue in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, methylene blue inhibited angiogenesis in a concentration-dependent manner. In addition, when methylene blue was combined with sodium nitroprusside, a spontaneous generator of nitric oxide, an inhibition of angiogenesis was evident which was comparable with that observed by the application of methylene blue alone. Sodium nitroprusside, alone, caused a significant inhibition in basal angiogenesis. These results provide evidence that methylene blue inhibits angiogenesis independently of nitric oxide pathway and suggest that methylene blue may be useful for treating angiogenesis-dependent human diseases. [source] Real-Time Contrast Imaging: A New Method to Monitor Capillary Recruitment in Human Forearm Skeletal MuscleMICROCIRCULATION, Issue 3 2008Alexandra H. Mulder ABSTRACT Objective: Muscle capillary perfusion can be measured by contrast-enhanced ultrasound. We examined whether a less time-consuming ultrasound technique, called "real-time imaging," could be used to measure capillary recruitment in human forearm skeletal muscle. Methods: We measured microvascular blood volume and microvascular flow velocity using bolus injections of contrast microbubbles after forearm muscle exercise and a two-hour infusion of insulin into the brachial artery (both associated with capillary recruitment) and after sodium nitroprusside infusion (no changes in flow distribution). Results: After an intravenous bolus injection of the contrast agent, the steady-state concentration of contrast agent in forearm muscle lasted long enough (approximately 190 seconds) for the duration of the measurements (which take 70,80 seconds), rendering the continuous infusion of microbubbles unnecessary. Microvascular blood-volume measurements showed a good short-time reproducibility and a good reproducibility after repositioning of the forearm. Reproducibility of microvascular flow velocity was too low. Exercise and insulin infusion both increased microvascular blood volume, consistent with capillary recruitment. Sodium nitroprusside had no effect. Conclusion: Real-time contrast imaging, after bolus injections of an ultrasound contrast agent, provides reliable information about capillary recruitment in human forearm skeletal muscle, and may offer a valuable tool in studying human (patho)physiology. [source] The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteriesAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2003A. Tasatargil Summary 1 The aim of the present study was to investigate the role of several possible neurotransmitters in mediating non-adrenergic, non-cholinergic (NANC) relaxation, and the effects of phosphodiesterase (PDE) III and V inhibitors on adrenergic and NANC relaxation in branch pulmonary artery (PA) of guinea-pig. 2 Under the NANC conditions, electrical field stimulation (EFS, 60 V, 0.2 ms, 20 Hz) induced a tetrodotoxin-sensitive relaxation of the histamine-precontracted PA rings. The nitric oxide (NO) synthase inhibitor NG -nitro- l -arginine methyl ester (l -NAME, 10,4 m) and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10,5 m) partially inhibited the EFS-induced relaxation. The inhibitory effect of l -NAME was reversed completely by l -arginine (10,3 m), but not d -arginine (10,3 m). 3 This NANC relaxation was attenuated by 8-phenyltheophylline (10,5 m), a P1 -purinoceptor antagonist. 4 The NANC response was potentiated by 10,6 m zaprinast, a type V PDE inhibitor, but was unaffected by 3 × 10,6 m milrinone, a type III PDE inhibitor. 5 Sodium nitroprusside (SNP) caused a concentration-dependent vasodilator effect which was potentiated by zaprinast, but unaffected by milrinone. Moreover, the effect of combination of zaprinast with milrinone was not significantly different from that observed with zaprinast alone. 6 Isoprenaline produced a concentration-dependent vasodilatation in branch PA of guinea-pig which was potentiated by both zaprinast and milrinone, the efficacy of milrinone being greater than zaprinast. 7 These results suggest that both nitrergic and purinergic pathways are involved in mediating the NANC relaxation in branch PA of guinea-pig. The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension. [source] Effect of nitric oxide on catharanthine production and growth of Catharanthus roseus suspension cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2005Maojun Xu Abstract Sodium nitroprusside (SNP) was used as the donor of nitric oxide (NO) to investigate its effect on catharanthine synthesis and the growth of Catharanthus roseus suspension cells. The results showed that SNP at high concentrations (10.0 and 20.0 mmol/L) stimulated catharanthine formation of C. roseus cells, but inhibited growth of the cells. Low concentrations of SNP (0.1 and 0.5 mmol/L) enhanced the growth of C. roseus cells, but had no effect on catharanthine synthesis. The maximum total catharanthine production was achieved by the addition of 0.5 and 10.0 mmol/L SNP to the cultures at day 0 and day 10, respectively, being about threefold of the control. NO-induced catharanthine production of C. roseus cells was strongly suppressed by jasmonic acid (JA) biosynthesis inhibitor ibuprofen (IBU) and nordihydroguaiaretic (NDGA). The result suggests that the stimulatory role of NO on catharanthine production is partially JA-dependent. © 2004 Wiley Periodicals, Inc. [source] Reciprocal regulation of human soluble and particulate guanylate cyclases in vivoBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006M Madhani Background & purpose: We demonstrated previously that reciprocal regulation of soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we investigated whether such an interaction contributes to vascular homeostasis in mice and humans in vivo. Experimental approach: Mean arterial blood pressure (MABP) changes in anaesthetized mice were monitored in response to i.v. administration of cGMP- and cAMP-dependent vasodilators in wild-type (WT), endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25, 50, 100, 200 pmol min -1) in the absence and presence of the NOS inhibitor NG -methyl-L-arginine (L-NMA; 4 ,mol min -1) and the control constrictor noradrenaline (240 pmol min -1) was assessed in healthy volunteers. Key results: Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP) produced dose-dependent reductions in MABP in WT animals that were significantly enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent reduction in MABP that was significantly greater than that in WT mice. Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT, eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance vasculature that was significantly greater in individuals lacking endothelium-derived NO (i.e. L-NMA treated). Conclusions & implications: These data demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These findings have implications for understanding the link between natriuretic peptide activity and cardiovascular risk. British Journal of Pharmacology (2006) 149, 797,801. doi:10.1038/sj.bjp.0706920 [source] Comparisons of cutaneous blood flow reactivity to norepinephrine and sodium nitroprusside between patients with heart transplantation and healthy subjectsCLINICAL TRANSPLANTATION, Issue 1 2001Ying-Tai Wu Heart transplant patients are reported to have impaired regulation of the microvasculature. The purpose of this study was to investigate the cutaneous blood flow and its reactivity to sodium nitroprusside (vasodilator, Nipride 0.1%) and norepinephrine (vasoconstrictor, Levophed 0.1%) in patients after heart transplantation in comparison to normal healthy individuals. Eighteen patients after heart transplantation and 16 healthy, nonsmoking individuals served as subjects of the study. Sodium nitroprusside and norepinephrine were introduced by iontophoresis to the skin of the right and left forearms, respectively. After measuring cutaneous blood flow reactivity in the pre-exercise state by laser Doppler flowmetry, subjects were then asked to close and open their fists for 2 min. The same measurements were repeated after exercise. Comparisons between the groups were carried out by the Wilcoxan signed rank test. The Mann,Whitney U -test was used for comparison between pre-exercise and post-exercise states. The results demonstrated that sodium nitroprusside significantly increased forearm cutaneous perfusion at rest but produced only a mild increase after exercise. This reactivity was significantly lower after exercise with no significant differences between groups. Norepinephrine decreased cutaneous blood flow at rest. The transplant patients were significantly less sensitive to norepinephrine before but not after exercise. The changes in norepinephrine reactivity with exercise were significantly different between groups (p<0.05). [source] Nitric oxide bioavailability modulates the dynamics of microvascular oxygen exchange during recovery from contractionsACTA PHYSIOLOGICA, Issue 2 2010D. M. Hirai Abstract Aim:, Lowered microvascular PO2 (PO2mv) during the exercise off-transient likely impairs muscle metabolic recovery and limits the capacity to perform repetitive tasks. The current investigation explored the impact of altered nitric oxide (NO) bioavailability on PO2mv during recovery from contractions in healthy skeletal muscle. We hypothesized that increased NO bioavailability (sodium nitroprusside: SNP) would enhance PO2mv and speed its recovery kinetics while decreased NO bioavailability (l -nitro arginine methyl ester: l -NAME) would reduce PO2mv and slow its recovery kinetics. Methods:,PO2mv was measured by phosphorescence quenching during transitions (rest,1 Hz twitch-contractions for 3 min,recovery) in the spinotrapezius muscle of Sprague,Dawley rats under SNP (300 ,m), Krebs-Henseleit (Control) and l -NAME (1.5 mm) superfusion conditions. Results:, Relative to recovery in Control, SNP resulted in greater overall microvascular oxygenation as assessed by the area under the PO2mv curve (PO2 AREA; Control: 3471 ± 292 mmHg s; SNP: 4307 ± 282 mmHg s; P < 0.05) and faster off-kinetics as evidenced by the mean response time (MRToff; Control: 60.2 ± 6.9 s; SNP: 34.8 ± 5.7 s; P < 0.05), whereas l -NAME produced lower PO2 AREA (2339 ± 444 mmHg s; P < 0.05) and slower MRToff (86.6 ± 14.5 s; P < 0.05). Conclusion:, NO bioavailability plays a key role in determining the matching of O2 delivery-to-O2 uptake and thus the upstream O2 pressure driving capillary-myocyte O2 flux (i.e. PO2mv) following cessation of contractions in healthy skeletal muscle. Additionally, these data support a mechanistic link between reduced NO bioavailability and prolonged muscle metabolic recovery commonly observed in ageing and diseased populations. [source] Systemic nitric oxide clamping in normal humans guided by total peripheral resistanceACTA PHYSIOLOGICA, Issue 2 2010J. A. Simonsen Abstract Aim:, We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. Methods:, Normal volunteers (23,28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor NG -nitro- l -arginine methyl ester (l -NAME) at 0.5 mg kg,1 h,1. One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l -NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. Results:,l -NAME increased MABP and total peripheral resistance (TPR, 1.02 ± 0.05 to 1.36 ± 0.07 mmHg s mL,1, mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL,1, P < 0.05). CO decreased with l -NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min,1, P < 0.01) and returned to control when SNP was added (6.0 ± 0.3 L min,1). A decrease in plasma noradrenaline (42%, P < 0.01) during l -NAME administration was completely reversed by SNP. Plasma renin activity decreased during l -NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l -NAME and remained elevated. Conclusions:, Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation. [source] Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated heartsACTA PHYSIOLOGICA, Issue 4 2002P. Tähepõld ABSTRACT Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia,reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose,response to phenylephrine (PHE), prostaglandin F2, (PGF2,) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 ± 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 ± 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application. [source] Does aerobic fitness influence microvascular function in healthy adults at risk of developing Type 2 diabetes?DIABETIC MEDICINE, Issue 4 2005A. R. Middlebrooke Abstract Aim To investigate whether aerobic fitness is associated with skin microvascular function in healthy adults with an increased risk of developing Type 2 diabetes. Methods Twenty-seven healthy normal glucose-tolerant humans with either a previous diagnosis of gestational diabetes or having two parents with Type 2 diabetes and 27 healthy adults who had no history of diabetes were recruited. Maximal oxygen uptake was assessed using an incremental exercise test to exhaustion. Skin microvascular function was assessed using laser Doppler techniques as the maximum skin hyperaemic response to a thermal stimulus (maximum hyperaemia) and the forearm skin blood flow response to the iontophoretic application of acetylcholine (ACh) and sodium nitroprusside. Results Maximal oxygen uptake was not significantly different in the ,at-risk' group compared with healthy controls. Maximum hyperaemia was reduced in those ,at risk' (1.29 ± 0.30 vs. 1.46 ± 0.33 V, P = 0.047); however, the peak response to acetylcholine or sodium nitroprusside did not differ in the two groups. A significant positive correlation was demonstrated between maximal oxygen uptake and maximum hyperaemia (r = 0.52, P = 0.006 l/min and r = 0.60, P = 0.001 ml/kg/min) and peak ACh response (r = 0.40, P = 0.04 l/min and r = 0.47, P = 0.013 ml/kg/min) in the ,at-risk' group when expressed in absolute (l/min) or body mass-related (ml/kg/min) terms. No significant correlations were found in the control group. Conclusions In this ,at-risk' group with skin microvascular dysfunction maximal oxygen uptake was not reduced compared with healthy controls. However, in the ,at-risk' group alone, individuals with higher levels of aerobic fitness also had better microvascular and endothelial responsiveness. [source] Individuals at increased coronary heart disease risk are characterized by an impaired microvascular function in skinEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2003R. G. IJzerman Abstract Background To investigate whether microvascular function in skin is a valid model to study the relationships between cardiovascular risk factors and microvascular function, we investigated skin microvascular function in individuals with increased coronary heart disease (CHD) risk. Materials and methods Forty-six healthy White individuals aged 30,70 years were studied. Coronary heart disease risk was assessed with the use of the CHD risk score according to the Framingham Heart Study, which is based on the risk factors age, blood pressure, cigarette smoking, total cholesterol, HDL cholesterol and diabetes. Endothelium-dependent and -independent vasodilation in skin were evaluated with laser Doppler after iontophoresis of acetylcholine and sodium nitroprusside. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. Results Coronary heart disease risk score (i.e. the 10-year probability of CHD) varied from 1,37%. Microvascular function decreased with increasing quartiles of CHD risk (for acetylcholine-mediated vasodilation: 687, 585, 420 and 326%, P = 0·002; for nitroprusside-mediated vasodilation: 776, 582, 513 and 366%, P = 0·02; for capillary recruitment: 49·9, 44·6, 27·2 and 26·7%, P = 0·001). These trends were similar in men and women (P for interaction > 0·2) and independent of body mass index. Conclusions Increased CHD risk is associated with an impaired endothelium-dependent vasodilatation and capillary recruitment in skin, suggesting that microvascular function in skin is a valid model to study the relationships between cardiovascular risk factors and microvascular function. [source] Effect of nitric oxide and NO synthase inhibition on nonquantal acetylcholine release in the rat diaphragmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000M. R. Mukhtarov Abstract After anticholinesterase treatment, the postsynaptic muscle membrane is depolarized by about 5 mV due to nonquantal release of acetylcholine (ACh) from the motor nerve terminal. This can be demonstrated by the hyperpolarization produced by the addition of curare (H-effect). The magnitude of the H-effect was decreased significantly to 3 mV when the nitric oxide (NO) donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) were applied to the muscle, or when NO production was elevated by adding l -arginine, but not d -arginine, as a substrate. The H-effect was increased to 8,9 mV by inhibition of NO synthase by l -nitroarginine methylester ( l -NAME), or by guanylyl cyclase inhibition by methylene blue and 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ). ODQ increased the H-effect to 7.3 ± 0.2 mV and diminished the SNP-induced decrease of the H-effect when applied together with SNP. The effects of NO donors and l -arginine were eliminated by adding reduced haemoglobin, an extracellular NO scavenger. The present results, together with earlier evidence for the presence of NO synthase in muscle fibres, indicate that nonquantal release of ACh is modulated by NO production in the postsynaptic cell. [source] Aerobic exercise acutely improves insulin- and insulin-like growth factor-1-mediated vasorelaxation in hypertensive ratsEXPERIMENTAL PHYSIOLOGY, Issue 5 2010Ai-Lun Yang Limited information is available concerning the effects of aerobic exercise on vasorelaxation in hypertension. The aim of this study was to investigate the effects of a single bout of aerobic exercise on insulin- and insulin-like growth factor-1 (IGF-1)-induced vasorelaxation in hypertensive rats. Four-month-old spontaneously hypertensive rats were randomly divided into a sedentary group (SHR) and an exercise group (SHR+Ex) subjected to a single bout of aerobic exercise conducted by treadmill running at 21 m min,1 for 1 h. Age-matched Wistar,Kyoto rats were used as a normotensive control group (WKY). Insulin- and IGF-1-induced vasorelaxant responses in the three groups were evaluated by using isolated aortic rings, with or without endothelial denudation, in organ baths. Possible roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) involved in the NO-dependent vasorelaxation were examined by adding selective inhibitors. The role of superoxide was also clarified by adding superoxide dismutase (SOD). In addition, the endothelium-independent vascular responses to sodium nitroprusside (SNP), a NO donor, were examined. The insulin- and IGF-1-induced vasorelaxation was significantly (P < 0.05) decreased in the SHR group compared with the WKY group. This decreased response in SHR was improved by exercise. These vasorelaxant responses among the three groups became similar after endothelial denudation and pretreatment with the PI3K inhibitor, NOS inhibitor or SOD. Also, no difference among groups was found in the SNP-induced vasorelaxation. We concluded that a single bout of aerobic exercise acutely improves insulin- and IGF-1-mediated vasorelaxation in an endothelium-dependent manner in hypertensive rats. [source] Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytesEXPERIMENTAL PHYSIOLOGY, Issue 4 2005Seung-Soo Chung The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current (Icat) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 ,m) completely inhibited Icat oscillations evoked by 1 ,m CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 ,m) almost completely prevented the inhibitory effect of SNP on Icat oscillations. 8-Bromo-guanosine 3,,5,-cyclic monophosphate (8-Br-cGMP; 30 ,m) in the pipette solution completely abolished Icat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 ,m) almost completely abolished the inhibitory effect of SNP on Icat oscillations. When the intracellular calcium concentration ([Ca2+]i) was held at a resting level using BAPTA (10 mm) and Ca2+ (4.6 ,m) in the pipette solution, CCh (1 ,m) evoked only the sustained component of Icat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP3; 30 ,m) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 ,m) on Icat oscillations. SNP significantly inhibited the Ca2+ release evoked by either CCh or IP3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on Icat oscillations are mediated, in part, by functional modulation of the IP3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner. [source] Iron regulatory protein-independent regulation of ferritin synthesis by nitrogen monoxideFEBS JOURNAL, Issue 16 2006Marc Mikhael The discovery of iron-responsive elements (IREs), along with the identification of iron regulatory proteins (IRP1, IRP2), has provided a molecular basis for our current understanding of the remarkable post-transcriptional regulation of intracellular iron homeostasis. In iron-depleted conditions, IRPs bind to IREs present in the 5,-UTR of ferritin mRNA and the 3,-UTR of transferrin receptor (TfR) mRNA. Such binding blocks the translation of ferritin, the iron storage protein, and stabilizes TfR mRNA, whereas the opposite scenario develops when iron in the intracellular transit pool is plentiful. Nitrogen monoxide (commonly designated nitric oxide; NO), a gaseous molecule involved in numerous functions, is known to affect cellular iron metabolism via the IRP/IRE system. We previously demonstrated that the oxidized form of NO, NO+, causes IRP2 degradation that is associated with an increase in ferritin synthesis [Kim, S & Ponka, P (2002) Proc Natl Acad Sci USA99, 12214,12219]. Here we report that sodium nitroprusside (SNP), an NO+ donor, causes a dramatic and rapid increase in ferritin synthesis that initially occurs without changes in the RNA-binding activities of IRPs. Moreover, we demonstrate that the translational efficiency of ferritin mRNA is significantly higher in cells treated with SNP compared with those incubated with ferric ammonium citrate, an iron donor. Importantly, we also provide definitive evidence that the iron moiety of SNP is not responsible for such changes. These results indicate that SNP-mediated increase in ferritin synthesis is, in part, due to an IRP-independent and NO+ -dependent post-transcriptional, regulatory mechanism. [source] Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin, KCl and acetylcholine following chronic alcohol consumption in vitroFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2001Tijen Utkan Ethanol has been reported to cause hypertension, the mechanism of which is unknown. Therefore, the effect of chronic ethanol consumption on vascular responsiveness and blood pressure was investigated. Systolic blood pressure was recorded weekly by tail-cuff method. Aortic rings from rats fed chow ad libitum or pair-fed liquid diets containing either ethanol (7.2% v/v) or isocaloric carbohydrate for 4 weeks were placed in organ chambers for isometric tension measurement. There was a mild but significant elevation of the systolic blood pressure in the alcohol-fed rats by week 1 compared to baseline measurements and this remained higher. No significant changes in reactivity of rat isolated aortas to phenylephrine, serotonin, endothelin-1 (ET-1) and KCl were seen in chronic ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol-fed aortic rings to the vasoconstrictors was also unchanged compared to controls. Chronic ethanol consumption, however, increased relaxation to acetylcholine with increased pD2 values, but did not alter relaxation to sodium nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent direct smooth muscle dilator. The results indicate that chronic ethanol consumption significantly potentiates endothelium-dependent relaxations in aortic rings, probably through interference with the production and/or the release of nitric oxide (NO) or adaptive alterations in muscarinic receptors on the endothelial cells, and that increased vascular responsiveness to several vasoconstrictors is not a mechanism responsible for the blood pressure elevation in the chronic alcohol consumption in rats. [source] Nitric oxide reduces astrocytic lactate production and induces neuronal vulnerability in stroke-prone spontaneously hypertensive ratsGLIA, Issue 4 2008Kazuo Yamagata Abstract Nitric oxide (NO) leads to neuronal death in ischemia/reperfusion (I/R), including stroke. Here, we examined the NO-induced vulnerability of neurons and lactate production by astrocytes in stroke-prone spontaneously hypertensive rats (SHRSP) in vitro. Neuronal cell death induced by the NO donor sodium nitroprusside (SNP) was significantly increased in SHRSP compared with Wistar kyoto rats (WKY). Furthermore, levels of lactate production by astrocytes were significantly reduced in SHRSP compared with WKY. At the same time, expressions of the lactate dehydrogenase (LDH) and monocarboxylate transporter 1 (MCT1) genes were significantly decreased by SNP in SHRSP compared with WKY. Moreover, in astrocytes isolated from SHRSP, the gene expression of isoforms of 6-phosphofracto-2-kinase (PFK2), a master regulator of glycolysis, namely PFK2.1, PFK2.2, PFK2.3, and PFK2.4, had deteriorated significantly. Notably, the SNP-evoked gene expression of PFK2.4 was lower in astrocytes of SHRSP than those of WKY. These results indicated that the neurons and astrocytes of SHRSP differed in responsiveness to SNP from those of WKY. This difference might explain the deficiency of energy and vulnerability to SNP of the neurons of SHRSP. © 2008 Wiley-Liss, Inc. [source] Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbitsINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2006BULENT SARAC Background:, The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25,35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. Methods:, In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls. Results:, Carbachol-induced relaxation responses and electrical field stimulation (EFS)-induced frequency-dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS-induced frequency-dependent contractions were significantly decreased in the hypothyroid group. Conclusions:, We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density. [source] DROUGHT STRESS: Comparative Time Course Action of the Foliar Applied Glycinebetaine, Salicylic Acid, Nitrous Oxide, Brassinosteroids and Spermine in Improving Drought Resistance of RiceJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 5 2010M. Farooq Abstract Worldwide rice productivity is being threatened by increased endeavours of drought stress. Among the visible symptoms of drought stress, hampered water relations and disrupted cellular membrane functions are the most important. Exogenous use of polyamines (PAs), salicylic acid (SA), brassinosteroids (BRs), glycinebetaine (GB) and nitrous oxide (NO) can induce abiotic stresses tolerance in many crops. In this time course study, we appraised the comparative role of all these substances to improve the drought tolerance in rice (Oryza sativa L.) cultivar Super-Basmati. Plants were subjected to drought stress at four leaf stage (4 weeks after emergence) by maintaining soil moisture at 50 % of field capacity. Pre-optimized concentrations of GB (150 mg l,1), SA (100 mg l,1), NO (100 ,mol l,1 sodium nitroprusside as NO donor), BR (0.01 ,m 24-epibrassinolide) and spermine (Spm; 10 ,m) were foliar sprayed at five-leaf stage (5 weeks after emergence). There were two controls both receiving no foliar spray, viz. well watered (CK1) and drought stressed (CK2). There was substantial reduction in allometric response of rice, gas exchange and water relation attributes by drought stress. While drought stress enhanced the H2O2, malondialdehyde (MDA) and relative membrane permeability, foliar spray of all the chemicals improved growth possibly because of the improved carbon assimilation, enhanced synthesis of metabolites and maintenance of tissue water status. Simultaneous reduction in H2O2 and MDA production was also noted in the plants treated with these substances. Drought tolerance was sturdily associated with the greater tissue water potential, increased synthesis of metabolites and enhanced capacity of antioxidant system. Of all the chemicals, foliar spray with Spm was the most effective followed by BR. [source] Nitrosative stress induced cytotoxicity in Giardia intestinalisJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2003D. Lloyd Abstract Aims: To investigate the antigiardial properties of the nitrosating agents: sodium nitrite, sodium nitroprusside and Roussin's black salt. Methods and Results: Use of confocal laser scanning microscopy and flow cytometry indicated permeabilization of the plasma membrane to the anionic fluorophore, DiBAC4(3) [bis(1,3-dibutylbarbituric acid) trimethine oxonol]. Loss of plasma membrane electrochemical potential was accompanied by loss of regulated cellular volume control. Changes in ultrastructure revealed by electron microscopy and capacity for oxygen consumption, were also consequences of nitrosative stress. Roussin's black salt (RBS), active at micromolar concentrations was the most potent of the three agents tested. Conclusions: These multitargeted cytotoxic agents affected plasma membrane functions, inhibited cellular functions in Giardia intestinalis and led to loss of viability. Significance and Impact of the Study: Nitrosative damage, as an antigiardial strategy, may have implications for development of chemotherapy along with suggesting natural host defence mechanisms. [source] Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channelJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5a 2008Yaohui Zhu Abstract Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from ,80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at ,25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability. [source] Methylene blue inhibits angiogenesis in chick chorioallontic membrane through a nitric oxide-independent mechanismJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2006N. Zacharakis Abstract Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study was to evaluate the effect of methylene blue in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, methylene blue inhibited angiogenesis in a concentration-dependent manner. In addition, when methylene blue was combined with sodium nitroprusside, a spontaneous generator of nitric oxide, an inhibition of angiogenesis was evident which was comparable with that observed by the application of methylene blue alone. Sodium nitroprusside, alone, caused a significant inhibition in basal angiogenesis. These results provide evidence that methylene blue inhibits angiogenesis independently of nitric oxide pathway and suggest that methylene blue may be useful for treating angiogenesis-dependent human diseases. [source] Nitric Oxide-Sensitive Guanylyl Cyclase Activity Inhibition Through Cyclic GMP-Dependent DephosphorylationJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Rut Ferrero Abstract: The soluble form of guanylyl cyclase (sGC) plays a pivotal role in the transduction of inter- and intracellular signals conveyed by nitric oxide. Here, a feedback inhibitory mechanism triggered by cyclic guanosine-3,,5,-monophosphate (cGMP)-dependent protein kinase (PKG) activation is described. Preincubation of chromaffin cells with C-type natriuretic peptide, which increased cGMP levels and activated PKG, or with cGMP-permeant analogue (which also activates PKG), in the presence of a broad-spectrum phosphodiesterase inhibitor, resulted in a decrease in subsequent sodium nitroprusside (SNP)-dependent cGMP elevations. This inhibitory effect was mimicked by activating a protein phosphatase and counteracted by the selective PKG inhibitor KT-5823 and by different protein phosphatase inhibitors. Immunoprecipitation of sGC from cells submitted to different treatments followed by immunodetection with antiphosphoserine antibodies (clone 4A9) showed changes in phosphorylation levels of the , subunit of sGC, and these changes correlated well with differences in SNP-elicited cGMP accumulations. Pretreatment of cells with several PKG inhibitors or protein phosphatase inhibitors produced an enhancement of SNP-stimulated cGMP rises without changing the SNP concentration required to produce half-maximal or maximal responses. Taken together, these results indicate that the catalytic activity of sGC is closely coupled to the phosphorylation state of its , subunit and that the tonic activity of PKG or its stimulation regulates sGC activity through dephosphorylation of the , subunit. [source] Regulation of Soluble Guanylyl Cyclase Activity by Oestradiol and Progesterone in the Hypothalamus But Not Hippocampus of Female RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2007A. Reyna-Neyra Oestradiol and progesterone act in the hypothalamus to coordinate the timing of lordosis and ovulation in female rats in part through regulation of nitric oxide (NO) and cyclic guanosine monophosphate (cyclic GMP) signalling pathways. Soluble guanylyl cyclase is an enzyme that produces cyclic GMP when stimulated by NO and plays a crucial role in the display of lordosis behaviour. We examined the effects of oestradiol and progesterone on the stimulation of cyclic GMP synthesis by NO-dependent and independent activators of soluble guanylyl cyclase in preoptic-hypothalamic and hippocampal slices. Ovariectomised Sprague-Dawley rats were injected with oestradiol (2 µg oestradiol benzoate, s.c.) or vehicle for 2 days. Progesterone (500 µg, s.c.) or vehicle was injected 44 h after the first dose of oestradiol. Rats were killed 48 h after the first oestradiol or vehicle injection, and hypothalamus and hippocampus were obtained. NO-dependent activation of soluble guanylyl cyclase was induced by NO donors, sodium nitroprusside or diethylamine NONOate; NO-independent activation of soluble guanylyl cyclase was induced with 3-(5,-hydroxymethyl-2,-furyl)-1-benzyl indazole and 5,-cyclopropyl-2-[1,2fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyridine-4-ylamine. The NO-dependent activators of soluble guanylyl cyclase produced a concentration-dependent increase in cyclic GMP accumulation and induced significantly greater cyclic GMP accumulation in preoptic-hypothalamic slices from animals treated with oestradiol and progesterone than in slices from rats injected with vehicle, oestradiol or progesterone alone. Hormones did not modify soluble guanylyl cyclase activation by NO-independent stimulators or influence NO content in preoptic-hypothalamic slices. Oestradiol and progesterone did not affect activation of soluble guanylyl cyclase in hippocampal slices by any pharmacological agent, indicating a strong regional selectivity for the hormone effect. Thus, oestradiol and progesterone, administered in vivo, enhance the ability of NO to activate soluble guanylyl cyclase in brain areas modulating female reproductive function without an effect on production of NO itself. [source] Nitric Oxide Mediates Inhibitory Effect of Interleukin-1, on Estrogen Production in Human Granulosa-Luteal CellsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2001Hisako Tobai Abstract Objective: To investigate the effect of IL-1, on NO production and steroidogenesis in human granulosa-luteal cells obtained from women undergoing in vitro fertilization procedures. Subjects and Methods:To investigate the effect of IL-1,, granulosa-luteal cells were cultured with various doses of IL-1, (0, 0.05, 0.5, 5, 50, 100 ng/ml), IL-1, (5 ng/ml) with NG -nitro-L-arginine-methyl ester (l-NAME), selective inhibitors of NOS, sodium nitroprusside (SNP), NO donors and Genistain, a tyrosine kinase inhibitor. Results:IL-1, induced a dose-dependent stimulation of NO production and inhibited the production of estradiol in a significant way in a dose-dependent manner. l-NAME significantly decreased NO production and increased the production of estradiol and progesterone. SNP significantly increased NO production and caused decreases in the production of both estradiol and progesterone. Genistain decreased NO production and significantly increased the production of estradiol and progesterone. Inducible NOS (iNOS) messenger RNA was present in granulosa-luteal cells before treatment with IL-1,. Conclusions:IL-1, stimulated NO production, and NO inhibited the production of estradiol. [source] N -acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2010Shuji Nakagawa Abstract We investigated whether N -acetylcysteine (NAC), a precursor of glutathione, could protect rabbit articular chondrocytes against nitric oxide (NO)-induced apoptosis and could prevent cartilage destruction in an experimental model of osteoarthritis (OA) in rats. Isolated chondrocytes were treated with various concentrations of NAC (0,2 mM). Apoptosis was induced by 0.75 mM sodium nitroprusside (SNP) dehydrate, which produces NO. Cell viability was assessed by MTT assay, while apoptosis was evaluated by Hoechst 33342 and TUNEL staining. Intracellular reactive oxygen species (ROS) and glutathione levels were measured, and expression of p53 and caspase-3 were determined by Western blotting. To determine whether intraarticular injection of NAC prevents cartilage destruction in vivo, cartilage samples of an OA model were subjected to H&E, Safranin O, and TUNEL staining. NAC prevented NO-induced apoptosis, ROS overproduction, p53 up-regulation, and caspase-3 activation. The protective effects of NAC were significantly blocked by buthionine sulfoximine, a glutathione synthetase inhibitor, indicating that the apoptosis-preventing activity of NAC was mediated by glutathione. Using a rat model of experimentally induced OA, we found that NAC also significantly prevented cartilage destruction and chondrocyte apoptosis in vivo. These results indicate that NAC inhibits NO-induced apoptosis of chondrocytes through glutathione in vitro, and inhibits chondrocyte apoptosis and articular cartilage degeneration in vivo. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:156,163, 2010 [source] Nitric oxide protects osteoblasts from oxidative stress-induced apoptotic insults via a mitochondria-dependent mechanism,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2006Chia-Chen Chang Abstract Nitric oxide (NO) contributes to the regulation of osteoblast activities. In this study, we evaluated the protective effects of NO pretreatment on oxidative stress-induced osteoblast apoptosis and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside (SNP) at a low concentration of 0.3 mM significantly increased cellular NO levels without affecting cell viability. However, when the concentration reached a high concentration of 2 mM, SNP increased the levels of intracellular reactive oxygen species and induced osteoblast injuries. Thus, administration of 0.3 and 2 mM SNP in osteoblasts were respectively used as sources of NO and oxidative stress. Pretreatment with NO for 24 h significantly ameliorated the oxidative stress-caused morphological alterations and decreases in alkaline phosphatase activity, and reduced cell death. Oxidative stress induced osteoblast death via an apoptotic mechanism, but NO pretreatment protected osteoblasts against the toxic effects. The mitochondrial membrane potential was significantly reduced following exposure to the oxidative stress. However, pretreatment with NO significantly lowered the suppressive effects. Oxidative stress increased cellular Bax protein production and cytochrome c release from mitochondria. Pretreatment with NO significantly decreased oxidative stress-caused augmentation of Bax and cytochrome c protein levels. In parallel with cytochrome c release, oxidative stress induced caspase-3 activation and DNA fragmentation. Pretreatment with NO significantly reduced the oxidative stress-enhanced caspase-3 activation and DNA damage. Results of this study show that NO pretreatment can protect osteoblasts from oxidative stress-induced apoptotic insults. The protective action involves a mitochondria-dependent mechanism. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1917,1925, 2006 [source] | ||||||||||||||||||||||||||||||||||||||||