Effects Of Sodium Nitroprusside Research Articles

Characteristics of reversible absorption-enhancing effect of sodium nitroprusside in rat small intestine

Nitric oxide (NO) donors increase the permeability of water-soluble compounds with neither loss of cell viability nor lactate dehydrogenase release. In addition, the rectal absorption of insulin has been reported to be remarkably enhanced in the presence of NO donors such as 1-Hydroxy-3-(3-aminopropyl)-3-isopropyltriazene 2-oxide (NOC5) and N-Ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC12). In this study, we examined the effect of sodium nitroprusside (SNP), which is used in clinical situations as a vasodilator, as a model NO donor on the ileal mucosa of rats. We used an in situ closed loop method in rat ileum to study changes in the permeability of fluorescein isothiocyanate dextran 4000 (FD-4) as a paracellular marker. The effect of SNP (1 and 10mg/kg) on the protein expression level of the claudin family was examined by Western blotting. The membrane permeation of FD-4 was increased but no mucosal lesion was observed upon the administration of SNP. Moreover, the protein expression level of the claudin family was not changed by the administration of SNP. When SNP was removed 2h after its administration, no significant change in the membrane permeation of FD-4 was observed. Moreover, no decrease of ileal membrane resistance or disruption of membrane structure was observed. The absorption-enhancing effect of SNP was associated with low injury and low toxicity. The reversibility of the effect of SNP was observed. Consequently, it was shown that SNP can be a useful absorption enhancer.

Nitric oxide suppresses L-type calcium currents in basilar artery smooth muscle cells in rabbits

Objectives: Nitric oxide (NO) is well known to be a vasodilator, and NO donor compounds are currently used for treating vasospasm following subarachnoid hemorrhage. However, the action mechanism of cerebral vascular relaxation is not yet clear. L-type calcium channels have been determined to play an essential role in smooth muscle contraction. To investigate the role of L-type calcium channels in NO-induced relaxation of basilar smooth muscle cells, we examined the effect of the NO donor, sodium nitroprusside (SNP) on calcium (Ca2+) currents using smooth muscle cells isolated from a rabbit basilar artery.Method: The smooth muscle cells were isolated from rabbit basilar artery by enzyme treatment. To identify L-type Ca2+ currents, we used cesium chloride, a potassium channel blocker and Bay K8644, an activator of L-type Ca2+ channel.Results: The L-type calcium currents (91±13·0 pA; n = 11) were significantly reduced by SNP (32±5 pA; n = 11; P<0·05). 1H-[1,2,4] Oxadiazolo [4,3-a] quinoxalin-1-one, a 3',5'-cyclic guanosine monophosphate inhibitor, blocked the effect of SNP on L-type Ca2+ currents, and similar results were obtained after the application of 7-nitroindazole, a specific NO synthase inhibitor. Furthermore, inward currents were enhanced by Bay K8644 (170±22 pA; n = 5) and were suppressed by SNP (54±13 pA; n = 5; P<0·05).Discussion: These results demonstrate that NO suppresses the L-type Ca2+ currents in rabbit basilar smooth muscle cells, and suggest that L-type Ca2+ channels may play a pivotal role in NO-induced vascular relaxation.

In Vitro Assessment of Clevidipine Using the Profilin1 Hypertensive Mouse Model

Hypertension represents a major risk factor for cardiovascular events, associating with vascular hypertrophy and dysfunction in resistance vessels. Clevidipine is a novel antihypertensive drug working as a selective calcium channel antagonist with an ultra-short half-life that lowers arterial blood pressure by reducing systemic arterial resistance. The aim was to assess the effect of clevidipine on the hypertrophic vessels of profilin1 hypertensive transgenic mice compared to sodium nitroprusside (SNP) and labetalol using wire myograph techniques. The effects of clevidipine, SNP and labetalol on the hypertrophic vessels were studied on mesenteric arterial function from 8 profilin1 hypertrophic mice and eight non-transgenic controls. Our results showed a significant difference between the effects of the three drugs on the hypertrophic mesenteric arteries of transgenic profilin1 mice compared to the non-transgenic controls. The half maximal effective concentration (EC50) of clevidipine, SNP and labetalol in profilin1 mice (1.90 ± 0.05, 0.97 ± 0.07, 2.80 ± 0.05 nM, respectively) were significantly higher than the EC50 in non-transgenic controls (0.91 ± 0.06, 0.32 ± 0.06, 0.80 ± 0.09 nM, respectively). Moreover, the increase in the EC50 for clevidipine (2-fold) to produce the same effect on both normal and hypertrophic arteries was less than that of SNP (3-fold) and labetalol (3.5-fold). Therefore, we concluded clevidipine exhibited the lowest dose shift to relax the hypertrophic vessels compared to SNP and labetalol in the profilin1 hypertrophic animal mouse model.

Changes in absorption and excretion of rhodamine 123 by sodium nitroprusside

Nitric oxide (NO) donors increase the permeability of water-soluble compounds with neither loss of cell viability nor lactate dehydrogenase release, but the involved mechanism is not fully understood. In this study, we focused on permeation via the transcellular route and P-glycoprotein, which is a typical ABC transporter. We examined the effect of sodium nitroprusside (SNP), which is an NO donor, on the membrane permeation of rhodamine 123 (Rho123), a representative P-gp substrate, and the change in expression level of ileal P-gp. We used an in situ closed loop method in rat ileum to study changes in the permeation of Rho123. The effects of SNP (1 and 10mg/kg) on the mdr-1a mRNA and P-gp protein expression levels were examined by real-time RT-PCR and Western blotting, respectively. The absorption and excretion of Rho123 were significantly increased in an SNP dose-dependent manner when compared with those with no addition, but no changes in protein expression level of P-gp in ileal BBM were observed by SNP administration. The relative activity of P-gp was not changed by SNP administration. On the other hand, the expression level of mdr-1a mRNA was induced by SNP administration. We indicated that SNP could increase the mucosal permeation of Rho123 via the transcellular route without an influence on P-gp, and we showed that this effect is temporary. SNP has no influence on P-gp function and protein expression level in the short term, but they may change in the long term.

Deciphering the possible mechanism of exogenous NO alleviating alkali stress on cucumber leaves by transcriptomic analysis

Alkali stress is a major factor that limits crop yield, and nitric oxide (NO) is involved in the regulation of plants tolerant to abiotic stress. In the present study, sodium nitroprusside (SNP), a NO donor, reversed the chlorosis of cucumber leaves caused by alkali stress. Physiological analysis indicated that application of SNP protected mesophyll cell ultrastructure from damage by alkali stress. SNP increased nutrient element utilization, pigment content, photosynthetic capacity and accumulation of organic acids. In this study, Solexa sequencing was used to investigate the effect of SNP on expression of genes involved in cucumber response to alkali stress. About 5.9 million (M) and 5.8M 21-nt cDNA tags were sequenced from the cDNA library of the alkali treatment and SNP treatment, respectively. When annotated, a total of 10,271 genes for the alkali stress treatment from the Solexa sequencing tags and 10,288 genes for SNP treatment were identified. We detected 901 differentially expressed genes in two samples, of which 437 and 464 of them were up- or down-regulated by SNP under alkali stress, respectively. The expression levels of 11 differentially expressed genes were confirmed by real-time RT-PCR. The trends observed agreed well with the Solexa expression profiles, although the degree of change was diverse in amplitude. Gene ontology analysis revealed that differentially expressed genes were mainly involved in response to abiotic stress, cellular metabolic process, photosynthesis, transmembrane transportation and organelle development, which were in accordance with physiological results.

Jasmonates modulate the promotion effects induced by SNP on root development of wheat under osmotic stress through lipoxygenase activation

We investigated promotion effects of exogenous sodium nitroprusside (SNP) on wheat seedling (Triticum aestivum L.) lateral root (LR) and root hair development, and the relationship between endogenous jasmonate (JA) production and activity changes of lipoxygenase (LOX) isoenzymes under osmotic stress generated by 15 % PEG-6000. Our results showed that 25 or 50 μM SNP could significantly increase LR length and number whether or not the seedlings were under PEG stress. When 50 μM cPTIO, 50 μM SHAM or 50 μM NDGA was supplemented, the promotion effects of SNP were blocked. SNP could also induce the production of endogenous JAs in roots, and 25 μM SNP induced the maximum JA content. The effect of SNP on JA production could also be blocked by adding cPTIO, SHAM or NDGA. Furthermore, the activity of lipoxygenase (LOX) in roots was affected by SNP; the maximal activity of LOX also occurred in the roots treated by 25 μM SNP under PEG stress, or 50 μM SNP without PEG stress. LOX isoenzymes in roots were detected by electrophoresis; the results showed that 25 μM SNP could noticeably increase the activities of LOXII and LOXIII under PEG stress. Our results suggest that, under osmotic stress generated by PEG, the promotion effects of exogenous SNP on wheat LR and root hair development could be mediated by endogenous JAs through LOX activation.

Is there a nitrergic modulation of the rat external anal sphincter?

Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter (EAS) is unknown. The aim of this study was to investigate whether there is a nitrergic nerve plexus that modulates the EAS, similar to that found in oesophageal striated muscle. An in vitro ring preparation of rat anal canal was used to evaluate the effects of the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine (L-NNA) and the NO donor sodium nitroprusside (SNP) on the EAS in conditions of neuromuscular blockade and the effect of SNP on nerve-evoked contractions. Immunohistological experiments were conducted to determine whether the neuronal isoform of nitric oxide synthase (nNOS) is present in the EAS. During direct muscle stimulation neither L-NNA (P = 0.32) nor SNP (P = 0.19) significantly changed the EF(50), which is the frequency at which 50% of maximal contraction is reached, compared with a time-dependent control. Nerve-evoked contractions were also not altered by addition of SNP to the tissue bath. Immunohistohistological experiments clearly showed co-localization of nNOS-positive nerve fibres at motor endplates of the oesophagus but not in the EAS. The internal anal sphincter was richly innervated by nitrergic fibres, but these did not extend into the EAS. In conclusion, there are no nitrergic motor fibres innervating the EAS, neurotransmission at the motor endplates is not affected by NO, and NO does not affect muscle force directly in conditions of neuromuscular blockade. There is, therefore, no evidence that EAS contraction is directly modulated by NO or by pudendal nitrergic fibres or diffusion from neighbouring nitrergic plexuses of the anal canal.

Vasodilatory effects of antivascular endothelium growth factor (VEGF) antibody, corticosteroid, and nitric oxide on the posterior ciliary arteries

The purpose of this study was to determine whether an antivascular endothelium growth factor (VEGF) antibody, a corticosteroid, and sodium nitroprusside (SNP) [a nitric oxide (NO) donor] are possible treatment agents for nonarteritic ischemic optic neuropathy (NAION) by clarifying their effects on high-K (potassium) solution-induced contraction in isolated rabbit and human posterior ciliary arteries (PCA). Vascular ring segments were cut from the distal section of the PCA and mounted in a double-myograph system. After obtaining the maximal contraction following the administration of high-K solution, bevacizumab as an anti-VEGF antibody, methylprednisolone as a corticosteroid, and SNP were administered separately. When a vasodilatory effect was observed, carboxy-PTIO (a NO scavenger) or L-NAME (a NO synthase inhibitor) was administered. Bevacizumab did not relax either the rabbit or the human PCA, whereas methylprednisolone relaxed both. Neither carboxy-PTIO nor L-NAME inhibited methylprednisolone-induced relaxation. SNP relaxed the rabbit PCA. Carboxy-PTIO inhibited SNP-induced relaxation, but L-NAME did not. In the human PCA, the vasodilatory effect of SNP was present, but weaker than in the rabbit PCA. A corticosteroid has NO-independent vasodilatory effects. Exogenous NO has a weak dilating effect in the human PCA. Therefore, corticosteroid could be effective for the treatment of NAION.

Sildenafil vs. Nitroprussiato de Sódio durante Teste de Reatividade Pulmonar pré-transplante cardíaco

Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 µg/kg/min) or SIL (100 mg, single dose). Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 ± 2.08 vs. 8.11 ± 1.81 cm/s, p = 0.002; SNP: 6.64 ± 1.51 vs. 7.72 ± 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation.

Effects of fenofibrate, a PPAR-α ligand, on the haemodynamics of glycerol-induced renal failure in rats

The modulating effect of peroxisome proliferator-activated receptor α ligand on haemodynamic effects of phenylepherine (PE), angiotensin II (AII), endothelin 1 (ET1), acetylcholine (Ach), sodium nitroprusside (SNP) and isoproterenol (ISO) were evaluated in glycerol-induced acute kidney injury in rats. The effect of PE on fenofibrate-treated animals was a dose-dependent increase in mean arterial blood pressure (MAP). For AII and ET1, MAP was also increased for the fenofibrate group but not in a dose-dependent fashion. On the medullary blood flow (MBF), while the lower doses of PE and AII increased the perfusion unit on the fenofibrate-treated group, the higher doses decreased the perfusion unit. The ET1 increased the perfusion unit on this group but not in dose-dependent fashion. The effects of PE and AII on the cortical blood flow (CBF) of fenofibrate-treated group is similar to that of MBF for the same group but not for ET1. The effect of Ach, SNP and ISO in all the groups was the decrease in MAP. ISO caused dose-dependent increase in MBF of fenofibrate-treated group. The effect of Ach, SNP and ISO on the CBF perfusion unit was that of the increase for the fenofibrate-treated group. The study showed that fenofibrate did not attenuate increased blood pressure induced by PE, AII and ET1 but caused enhanced vasodilation by Ach, SNP and ISO.

Interactive role of nitric oxide and calcium chloride in enhancing tolerance to salt stress

Nitric oxide (NO), a small diffusible, ubiquitous bioactive molecule, acts as prooxidant as well as antioxidant, and also regulates remarkable spectrum of plant cellular mechanisms. The present work was undertaken to investigate the role of nitric oxide donor sodium nitroprusside (SNP) and/or calcium chloride (CaCl2) in the tolerance of excised mustard leaves to salt stress. After 24h, salt stressed leaves treated with SNP and/or CaCl2, showed an improvement in the activities of carbonic anhydrase (CA) and nitrate reductase (NR), and leaf chlorophyll (Chl) content, leaf relative water content (LRWC) and leaf ion concentration as compared with the leaves treated with NaCl only. Salinity stress caused a significant increase in H2O2 content and membrane damage which is witnessed by enhanced levels of thiobarbituric acid reactive substances (TBARS) and electrolyte leakage. By contrast, such increases were blocked by the application of 0.2mM SNP and 10mM CaCl2 to salt stressed leaves. Application of SNP and/or CaCl2 alleviated NaCl stress by enhancing the activities of antioxidative enzymes viz. superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX) and glutathione reductase (GR) and by enhancing proline (Pro) and glycinebetaine (GB) accumulation with a concomitant decrease in H2O2 content, TBARS and electrolyte leakage, which is manifested in the tolerance of plants to salinity stress. Moreover, application of SNP with CaCl2 was more effective to reduce the detrimental effects of NaCl stress on excised mustard leaves. In addition to this, ameliorating effect of SNP was not effective in presence of NO scavenger cPTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide]. To put all these in a nut shell, the results advocate that SNP in association with CaCl2 plays a role in enhancing the tolerance of plants to salt stress by improving antioxidative defence system, osmolyte accumulation and ionic homeostasis.

Effect of nitric oxide on epithelial ion transports in noncystic fibrosis and cystic fibrosis human proximal and distal airways

The airways of patients with cystic fibrosis (CF) exhibit decreased nitric oxide (NO) concentrations, which might affect airway function. The aim of this study was to determine the effects of NO on ion transport in human airway epithelia. Primary cultures of non-CF and CF bronchial and bronchiolar epithelial cells were exposed to the NO donor sodium nitroprusside (SNP), and bioelectric variables were measured in Ussing chambers. Amiloride was added to inhibit the Na(+) channel ENaC, and forskolin and ATP were added successively to stimulate cAMP- and Ca(2+)-dependent Cl(-) secretions, respectively. The involvement of cGMP was assessed by measuring the intracellular cGMP concentration in bronchial cells exposed to SNP and the ion transports in cultures exposed to 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, an inhibitor of the soluble guanylate cyclase (ODQ), or to 8Z, a cocktail of 8-bromo-cGMP and zaprinast (phosphodiesterase 5 inhibitor). SNP decreased the baseline short-circuit current (I(sc)) and the changes in I(sc) induced by amiloride, forskolin, and ATP in non-CF bronchial and bronchiolar cultures. The mechanism of this inhibition was studied in bronchial cells. SNP increased the intracellular cGMP concentration ([cGMP](i)). The inhibitory effect of SNP was abolished by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO scavenger (PTIO) and ODQ and was partly mimicked by increasing [cGMP](i). In CF cultures, SNP did not significantly modify ion transport; in CF bronchial cells, 8Z had no effect; however, SNP increased the [cGMP](i). In conclusion, exogenous NO may reduce transepithelial Na(+) absorption and Cl(-) secretion in human non-CF airway epithelia through a cGMP-dependent pathway. In CF airways, the NO/cGMP pathway appears to exert no effect on transepithelial ion transport.

Exogenous nitric oxide (NO) increased antioxidant capacity of cucumber hypocotyl and radicle under salt stress

Excessive accumulation of reactive oxygen species (ROS) under salt stress can cause oxidative damage, nitric oxide (NO) is considered as a functional molecule in alleviating salt stress to plants through modulating antioxidant metabolism. In the present experiment, effects of sodium nitroprusside (SNP), a NO donor, on the growth, and antioxidant capacity of cucumber hypocotyls and radicles as well as root tip ultrastructure were studied under 100mM NaCl stress. NaCl treatment significantly induced accumulation of H2O2 and thiobarbituric acid-reactive substances (TBARS) in cucumber hypocotyls and radicles, and application of 100μM SNP stimulated ROS-scavenging enzymes and increased α,α-diphenyl-β-picryllhydrazyl (DPPH) scavenging activity, chelating activity of ferrous ions and hydroxyl radical (OH) scavenging activity, resulting in lower lipid peroxidation induced by NaCl stress. The ultrastructure of the root tip cells was investigated, NaCl stress induced disturbance of mitochondria and the cell wall, and SNP treatment alleviated the ultrastructure disturbance induced by NaCl stress. The above effects of SNP were reversed by addition of hemoglobin (a NO scavenger), which indicated that the function of SNP alleviating lipid perioxidation in NaCl-treated cucumber hypocotyls and radicles depended on NO. Therefore, it can be concluded that the increasing antioxidant capacity by NO might be greatly responsible for its function in alleviating the inhibition of cucumber hypocotyls and radicles growth and cell ultrastructure damage by salt stress.

The nitric oxide donor sodium nitroprusside requires the 18 kDa Translocator Protein to induce cell death

Various studies have shown that several lethal agents induce cell death via the mitochondrial 18 kDa Translocator Protein (TSPO). In this study we tested the possibility that nitric oxide (NO) is the signaling component inducing the TSPO to initiate cell death process. Cell viability assays included Trypan blue uptake, propidium iodide uptake, lactate dehydrogenase release, and DNA fragmentation. These assays showed that application of the specific TSPO ligand PK 11195 reduced these parameters for the lethal effects of the NO donor sodium nitroprusside (SNP) by 41, 27, 40, and 42 %, respectively. TSPO silencing by siRNA also reduced the measured lethal effects of SNP by 50 % for all of these four assays. With 2,3-bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxyanilide (XTT) changes in metabolic activity were detected. PK 11195 and TSPO knockdown fully prevented the reductions in XTT signal otherwise induced by SNP. Collapse of the mitochondrial membrane potential was studied with the aid of JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine chloride). PK 11195 and TSPO knockdown reduced, respectively by 36 and 100 %, the incidence of collapse of the mitochondrial membrane potential otherwise induced by SNP. 10-N-Nonyl-Acridine Orange (NAO) was used to detect mitochondrial reactive oxygen species generation due to SNP. PK 11195 and TSPO knockdown reduced this effect of SNP by 65 and 100 %, respectively. SNP did not affect TSPO protein expression and binding characteristics, and also did not cause TSPO S-nitrosylation. However, β-actin and various other proteins (not further defined) were S-nitrosylated. In conclusion, TSPO is required for the lethal and metabolic effects of the NO donor SNP, but TSPO itself is not S-nitrosylated.

Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro: implications for anthracycline-induced cardiotoxicity

Sodium nitroprusside (SNP) is used clinically as a rapid-acting vasodilator and in experimental models as donor of nitric oxide (NO). High concentrations of NO have been reported to induce cardiotoxic effects including apoptosis by the formation of reactive oxygen species. We have therefore investigated effects of SNP on the myofibrillar cytoskeleton, contractility and cell death in long-term cultured adult rat cardiomyocytes at different time points after treatment. Our results show, that SNP treatment at first results in a gradual increase of cytoskeleton degradation marked by the loss of actin labeling and fragmentation of sarcomeric structure, followed by the appearance of TUNEL-positive nuclei. Already lower doses of SNP decreased contractility of cardiomyocytes paced at 2 Hz without changes of intracellular calcium concentration. Ultrastructural analysis of the cultured cells demonstrated mitochondrial changes and disintegration of sarcomeric alignment. These adverse effects of SNP in cardiomyocytes were reminiscent of anthracycline-induced cardiotoxicity, which also involves a dysregulation of NO with the consequence of myofibrillar degradation and ultimately cell death. An inhibition of the pathways leading to the generation of reactive NO products, or their neutralization, may be of significant therapeutic benefit for both SNP and anthracycline-induced cardiotoxicity.

Nitric oxide inhibits the expression of AT1 receptors in neurons

We have previously observed an increased of angiotensin II (ANG II) type 1 receptor (AT(1)R) with enhanced AT(1)R-mediated sympathetic outflow and concomitant downregulation of neuronal nitric oxide (NO) synthase (nNOS) with reduced NO-mediated inhibition from the paraventricular nucleus (PVN) in rats with heart failure. To test the hypothesis that NO exerts an inhibitory effect on AT(1)R expression in the PVN, we used primary cultured hypothalamic cells of neonatal rats and neuronal cell line NG108-15 as in vitro models. In hypothalamic primary culture, NO donor sodium nitroprusside (SNP) induced dose-dependent decreases in mRNA and protein of AT(1)R (10(-5) M SNP, AT(1)R protein was 10 ± 2% of control level) while NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) induced dose-dependent increases in mRNA and protein levels of AT(1)R (10(-5) M l-NMMA, AT(1)R protein was 148 ± 8% of control level). Similar effects of SNP and l-NMMA on AT(1)R expression were also observed in NG108-15 cell line (10(-6) M SNP, AT(1)R protein was 30 ± 4% of control level while at the dose of 10(-6) M l-NMMA, AT(1)R protein was 171 ± 15% of the control level). Specific inhibition of nNOS, using antisense, caused an increase in AT(1)R expression while overexpression of nNOS, using adenoviral gene transfer (Ad.nNOS), caused an inhibition of AT(1)R expression in NG108 cells. Antisense nNOS transfection augmented the increase while Ad.nNOS infection blunted the increase in intracellular calcium concentration in response to ANG II treatment in NG108 cells. In addition, downregulation of AT(1)R mRNA as well as protein level in neuronal cell line in response to S-nitroso-N-acetyl pencillamine (SNAP) treatment was blocked by protein kinase G (PKG) inhibitor, while the peroxynitrite scavenger deforxamine had no effect. These results suggest that NO acts as an inhibitory regulator of AT(1)R expression and the activation of PKG is the required step in the regulation of AT(1)R gene expression via cGMP-dependent signaling pathway.

Sodium nitroprusside (SNP) alleviates the oxidative stress induced by NaHCO3 and protects chloroplast from damage in cucumber

Oxidative damage is often induced by abiotic stress, nitric oxide (NO) is considered as a functional molecule in modulating antioxidant metabolism of plants. In the present study, effects of sodium nitroprusside (SNP), a NO donor, on the phenotype, antioxidant capacity and chloroplast ultrastructure of cucumber leaves were studied under NaHCO 3 stress. 30 mM NaHCO 3 treatment significantly induced accumulation of H 2O2 and thiobarbituric acid-reactive substances (TBARS) in cucumber leaves, and led to serious electrolyte leakage. Application of 100 µM SNP stimulated reactive oxygen species (ROS)scavenging enzymes and increased antioxidant capacity, resulting in lower lipid peroxidation and membrane damage induced by NaHCO 3 stress. As a main organelle of ROS formation, chloroplast ultrastructure was seriously damaged by NaHCO 3 stress and SNP treatment obviously reversed the damage. On the contrary, the above effects of SNP were not observed by application of potassium ferrocyanide which is an analog of SNP that does not release NO. Therefore, it could be concluded that the NO from SNP might account for the alleviating effect of NaHCO 3 stress on cucumber plants.

Oxidative stress and NADPH oxidase participation on the hypotensive responses of [Ru(terpy)(bdq)NO+]3+ (TERPY) in spontaneously hypertensive rats (SHR)

The hypotensive effect of the new NO donor TERPY was evaluated in Wistar (WST) and SHR after pre‐infusion with an in bolus injection of Tempol (superoxide dismutase mimetic; 30 mg/Kg) and Apocynin (NADPH oxidase inhibitor; 30mg/Kg) and the effects were compared to sodium nitroprusside (SNP) effects (35 μg/Kg). The hypotensive effect of both NO donors was increased in SHR, but only SNP increased the HR (heart rate). The Tempol infusion decreased the mean arterial pressure (MAP) in WST and SHR, but did not alter the HR and reduced the TERPY effect. In the presence of Tempol, the hypotension evoked by TERPY is not different between WST and SHR, and the SNP effect was increased in SHR. Apocynin induced hypotension was more significant in SHR, but it decreased the HR in both groups. In apocynin infused rats, the hypotension induced by TERPY was higher in SHR, but there was no difference in the effect of SNP. These results indicates that superoxide anions is involved in the difference of the hypotensive effect between Wistar and SHR and that NADPH oxidase participates in the hypotensive response of SNP but not to TERPY.

Small Bolus of Esmolol Effectively Prevents Sodium Nitroprusside-Induced Reflex Tachycardia Without Adversely Affecting Blood Pressure

Hypotensive anesthesia with sodium nitroprusside (SNP) often is associated with reflex tachycardia. The purpose of this study was to investigate whether a small bolus of esmolol could counteract SNP-induced reflex tachycardia and sympathetic activation without affecting blood pressure. Using a time-series study design, 27 healthy young patients scheduled for mandibular osteotomy were enrolled in this study. General anesthesia was maintained with 2% sevoflurane and 67% nitrous oxide in oxygen. SNP was administered to decrease the mean arterial pressure to 55 to 65 mm Hg. When heart rate (HR) increased reflexively to higher than 95 beats/min from SNP-induced hypotension, esmolol 0.5 mg/kg was given. Blood pressure and HR were measured, and the low-frequency component (0.04 to 0.15 Hz) of systolic blood pressure variability and high-frequency component (0.15 to 0.4 Hz) of HR variability were calculated to evaluate the autonomic condition. Data were analyzed using 1-way analysis of variance after multiple comparisons or t test. P < .05 was considered statistically significant. Of the 27 patients analyzed, 19 patients (70%) required esmolol. In these patients, SNP caused an increase in the low-frequency component of systolic blood pressure variability and a decrease in the high-frequency component of HR variability, leading to tachycardia (HR range, 95.9 ± 7.3 to 106.7 ± 7.4 beats/min; P < .001). Esmolol suppressed the effects of SNP on the low-frequency component of systolic blood pressure variability and high-frequency component of HR variability, resulting in an immediate decrease in HR to 86.9 ± 6.2 beats/min (P < .001), whereas mean arterial pressure remained unchanged. A small bolus of esmolol can suppress reflex tachycardia without significantly changing mean arterial pressure. Thus, esmolol restores the autonomic imbalance induced by SNP during hypotensive anesthesia.

Nitric oxide exacerbates Al-induced inhibition of root elongation in rice bean by affecting cell wall and plasma membrane properties

Aluminum (Al) toxicity is one of the most widespread problems for crop production on acid soils, and nitric oxide (NO) is a key signaling molecule involved in the mediation of various biotic and abiotic stresses in plants. Here we found that exogenous application of the NO donor sodium nitroprusside (SNP) exacerbated the inhibition of Al-induced root growth in rice bean [Vigna umbellata (Thunb.) Ohwi & Ohashi ‘Jiangnan’, Fabaceae]. This was accompanied by an increased accumulation of Al in the root apex. However, Al treatments had no effect on endogenous NO concentrations in root apices. These results indicate that a change in NO concentration is not the cause of Al-induced root growth inhibition and the adverse effect of SNP on Al-induced root growth inhibition should result from increased Al accumulation. Al could significantly induce citrate efflux but SNP had no effects on citrate efflux either in the absence or presence of Al. On the other hand, SNP pretreatment significantly increased Al-induced malondialdehyde accumulation and Evans Blue staining, indicating an intensification of the disruption of plasma membrane integrity. Furthermore, SNP pretreatment also caused greater induction of pectin methylesterase activity by Al, which could be the cause of the increased Al accumulation. Taken together, it is concluded that NO exacerbates Al-induced root growth inhibition by affecting cell wall and plasma membrane properties.