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1.
Zhongguo Zhong Yao Za Zhi ; 45(2): 321-330, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237314

RESUMO

Atropa belladonna seedlings were used as experimental materials and cultivated by soil culture method. Different concentrations(0,0.05,0.1,0.2,0.5 mmol·L~(-1))of NO donor sodium nitroprusside(SNP) were sprayed on the leaves. The effects of different concentrations of SNP and different treatment time(4,8,12,16 d) on nitrogen metabolism, secondary metabolite content, precursor content of tropane alkaloid synthesis pathway and expression of key enzyme genes under 100 mmol·L~(-1) NaCl stress were studied. The results showed that with the prolongation of salt stress, the nitrogen metabolism and the accumulation of secondary metabolites of A. belladonna were inhibited to some extent. After treatment with different concentrations of exogenous SNP, the ammonium nitrogen content decreased dramatically, and the contents of nitrate nitrogen, free amino acid, soluble protein and the activities of key enzymes of nitrogen metabolism(NR, GS, GDH) were all greatly improved; the contents of precursor amino acids(ornithine, arginine) and polyamines(Put, Spd, Spm) in the secondary metabolic pathway have increased to varying degrees. The qRT-PCR analysis showed that exogenous SNP treatment can effectively promote the high expression of key enzyme genes PMT, TRⅠ and H6H in the secondary metabolic pathway of A. belladonna, and the production of hyoscyamine and scopolamine were increased notably. In summary, the application of appropriate concentration of SNP can effectively alleviate the inhibition of salt stress on the nitrogen metabolism and secondary metabolism of Atropa belladonna, and enhance its salt tolerance. Overall, 0.1 mmol·L~(-1) and 0.2 mmol·L~(-1) SNP treatment achieved the most remarkable effect.


Assuntos
Atropa belladonna/metabolismo , Hiosciamina/análise , Nitrogênio/metabolismo , Escopolamina/análise , Nitroprussiato , Metabolismo Secundário , Cloreto de Sódio , Estresse Fisiológico
2.
Am J Physiol Heart Circ Physiol ; 318(4): H937-H946, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142360

RESUMO

The arterial baroreflex has dominant control over multiunit muscle sympathetic nerve activity (MSNA) burst occurrence, but whether this extends to all single units or is influenced by resting blood pressure status is unclear. In 22 men (32 ± 8 yr), we assessed 68 MSNA single units during sequential bolus injections of nitroprusside and phenylephrine (modified Oxford). Sympathetic baroreflex sensitivity (sBRS) was quantified as the weighted negative linear regression slope between diastolic blood pressure (DBP) and single-unit spike firing probability and multiple spike firing. Strong negative linear relationships (r ≥ -0.50) between DBP and spike firing probability were observed in 63/68 (93%) single units (-2.27 ± 1.27%·cardiac cycle-1·mmHg-1 [operating range, 18 ± 8 mmHg]). In contrast, only 45/68 (66%) single units had strong DBP-multiple spike firing relationships (-0.13 ± 0.18 spikes·cardiac cycle-1·mmHg-1 [operating range, 14 ± 7 mmHg]). Participants with higher resting DBP (65 ± 3 vs. 77 ± 3 mmHg, P < 0.001) had similar spike firing probability sBRS (low vs. high, -2.08 ± 1.08 vs. -2.46 ± 1.42%·cardiac cycle-1·mmHg-1, P = 0.33), but a smaller sBRS operating range (20 ± 6 vs. 16 ± 9 mmHg, P = 0.01; 86 ± 24 vs. 52 ± 25% of total range, P < 0.001) and a higher proportion of single units without arterial baroreflex control outside this range [6/31 (19%) vs. 21/32 (66%), P < 0.001]. Participants with higher resting DBP also had fewer single units with arterial baroreflex control of multiple spike firing (79 vs. 53%, P = 0.04). The majority of MSNA single units demonstrate strong arterial baroreflex control over spike firing probability during pharmacological manipulation of blood pressure. Changes in single-unit sBRS operating range and control of multiple spike firing may represent altered sympathetic recruitment patterns associated with the early development of hypertension.NEW & NOTEWORTHY Muscle sympathetic single units can be differentially controlled during stress. In contrast, we demonstrate that 93% of single units maintain strong arterial baroreflex control during pharmacological manipulation of blood pressure. Interestingly, the operating range and proportion of single units that lose arterial baroreflex control outside of this range are influenced by resting blood pressure levels. Altered single unit, but not multiunit, arterial baroreflex control may represent changes in sympathetic recruitment patterns in early stage development of hypertension.


Assuntos
Artérias/fisiologia , Barorreflexo , Pressão Sanguínea , Músculo Liso Vascular/fisiologia , Sistema Nervoso Simpático/fisiologia , Adulto , Artérias/efeitos dos fármacos , Humanos , Masculino , Condução Nervosa , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Vasodilatadores/farmacologia
3.
Am J Physiol Heart Circ Physiol ; 318(4): H925-H936, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142378

RESUMO

Using high-fidelity micromanometers and flow velocity sensors at right heart catheterization, we compared pulmonary hemodynamics and wave reflections in age-matched normal adults and those with atrial septal defects, separated into three subgroups based on levels of mean pulmonary artery pressure: low (<17 mmHg), intermediate (17-26 mmHg), high (>26 mmHg). We made baseline measurements in all groups and after intravenous sodium nitroprusside in the subgroups. All of the subgroups had higher than normal baseline pulmonary flows and corresponding power that did not differ among the subgroups. The pulmonary vascular resistance, input resistance, and characteristic impedance in the subgroups did not differ from normal. Aside from the elevated flow and power, the hemodynamics in the low subgroup did not differ from normal. The intermediate subgroup had significantly higher than normal right ventricular and pulmonary artery pressures, wave reflections, and shorter wave reflection time, which all reverted to normal after nitroprusside. The high subgroup had similar changes as the intermediate subgroup. Unlike that subgroup, however, the pressures, wave reflections, and reflection return time did not revert to normal after nitroprusside. Hence, elevated wave reflections, but not resistance or characteristic impedance, are the hallmark of pulmonary hypertension in adults with atrial septal defects. Our results demonstrate that detailed measurements of hemodynamics and assessment of responsiveness to vasodilators provide important information about the pulmonary circulation in atrial septal defect. Coupled with studies after defect closure, those results may be a better foundation than current ones for clinical decisions.


Assuntos
Comunicação Interatrial/fisiopatologia , Hemodinâmica , Circulação Pulmonar , Adulto , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Nitroprussiato/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Vasodilatadores/farmacologia
4.
Life Sci ; 250: 117586, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222464

RESUMO

AIM: The inward rectifier K+ (Kir) channels and prostanoids are important factors in regulating vascular tone, but the relationship between them has not been well studied. We aimed to study the involvement of prostanoids in regulating Kir activity in the rat intrarenal arteries (RIRAs). MAIN METHODS: The vascular tone of isolated RIRAs was recorded with a wire myograph. The intracellular Ca2+ concentrations ([Ca2+]i) and Kir currents were measured with a Ca2+-sensitive fluorescence probe and patch clamp, respectively, in the arterial smooth muscle cell (ASMC) freshly isolated from RIRAs. Kir2.1 expression in RIRAs was assayed by Western blotting. KEY FINDINGS: At 0.03-1.0 mM, BaCl2 (a specific Kir blocker) concentration-dependently contracted RIRAs and elevated [Ca2+]i levels. Mild stimulations with various vasoconstrictors at low concentrations significantly potentiated RIRA contraction induced by Kir closure with BaCl2. In both the quiescent and the stimulated RIRAs, cyclooxygenase inhibition and thromboxane-prostanoid receptor (TPR) antagonism depressed BaCl2-induced RIRA contraction, while nitric oxide (NO) synthetase inhibition and endothelium-denudation enhanced the contraction. Kir2.1 expression was significantly more abundant in smaller RIRAs. Ba2+-sensitive Kir currents were depressed by TPR agonist U46619 while increased by NO donor sodium nitroprusside. SIGNIFICANCE: The present results reveal that vasoconstrictor stimulation augments RIRA contraction induced by Kir closure with Ba+ and indicate that prostanoid synthesis followed by TPR activation is involved in the modulation of the myocyte Kir activity. This study suggests that prostanoid synthesis and TPR may be potential targets for dysfunctions in renal blood circulation.


Assuntos
Miócitos de Músculo Liso/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Prostaglandinas/metabolismo , Artéria Renal/citologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Artérias/metabolismo , Cálcio/metabolismo , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Rim/irrigação sanguínea , Masculino , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores de Prostaglandina/metabolismo , Tromboxanos/metabolismo , Vasoconstritores/farmacologia
5.
BMC Complement Med Ther ; 20(1): 23, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32020892

RESUMO

BACKGROUND: Chondrocyte apoptosis activated by the mitochondrial dependent pathway serves a crucial role in cartilage degeneration of osteoarthritis (OA). In the present study, the protective effects of CMCS against sodium nitroprusside (SNP)-induced chondrocyte apoptosis were evaluated and the underlying molecular mechanisms were elucidated. METHODS: Chondrocytes were isolated from articular cartilage of SD rats and identified by type II collagen immunohistochemistry. The chondrocytes stimulated with or without SNP to induce apoptosis, were treated by CMCS for various concentrations. The cell viability were determined by MTT and LDH assays. Cell apoptotic ratio was determined by Annexin V-FITC/PI staining. Mitochondrial membrane potential (ΔΨm) was detected by using Rhodamine123 (Rho123) staining. To understand the mechanism, the mRNA expression levels of Bcl-2, Bax, cytochrome c (Cyt c) and cleaved caspase-3 were detected by real-time PCR and western blot analysis, respectively. RESULTS: It was shown using the MTT and LDH assays that CMCS protected the viability of chondrocyte against SNP damage. Annexin V-FITC/PI and Rho123 staining showed that CMCS not only inhibited the cell apoptosis but also restored the reduction of the ΔΨm in chondrocytes. In SNP-induced chondrocytes, CMCS down-regulated the expression of Bax, Cyt c and cleaved caspase-3 but upregulated the expression of Bcl-2, as shown by real-time PCR and western blot. CONCLUSIONS: Taken together, these results indicated that CMCS has the protective effect on chondrocytes against SNP-induced apoptosis, at least partly, via inhibiting the mitochondrial dependent apoptotic pathway. Thus, CMCS may be potentially used as a biological agent for prevention and treatment of OA.


Assuntos
Apoptose/efeitos dos fármacos , Quitosana/farmacologia , Condrócitos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Animais , Células Cultivadas , Quitosana/química , Condrócitos/citologia , Óxido Nítrico , Nitroprussiato , Ratos , Ratos Sprague-Dawley
6.
J Plant Physiol ; 246-247: 153133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32065920

RESUMO

Reports on the effect of nitric oxide (NO) or reactive oxygen species (ROS) on photosynthesis and respiration in leaf tissues are intriguing; therefore, the effects of exogenous addition of sodium nitroprusside (SNP, releases NO) or H2O2 on the photosynthetic O2 evolution and respiratory O2 uptake by mesophyll protoplasts in pea (Pisum sativum) were evaluated in the present study. Low concentrations of SNP or H2O2 were used to minimize nonspecific effects. The effects of NO or H2O2 on respiration and photosynthesis were different. The presence of NO decreased the rate of photosynthesis but caused a marginal stimulation of dark respiration. Conversely, externally administered H2O2 drastically decreased the rate of respiration but only slightly decreased photosynthesis. The PS I activity was more sensitive to NO than PS II. On the other hand, 100 µM H2O2 had no effect on the photochemical reactions of either PS I or PS II. The sensitivity of photosynthesis to antimycin A or SHAM (reflecting the interplay between chloroplasts and mitochondria) was not affected by NO. By contrast, H2O2 markedly decreased the sensitivity of photosynthesis to antimycin A and SHAM. It can be concluded that chloroplasts are the primary targets of NO, while mitochondria are the primary targets of ROS in plant cells. We propose that H2O2 can be an important signal to modulate the crosstalk between chloroplasts and mitochondria.


Assuntos
Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Nitroprussiato/metabolismo , Ervilhas/fisiologia , Fotossíntese , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/administração & dosagem , Células do Mesofilo/efeitos dos fármacos , Células do Mesofilo/fisiologia , Óxido Nítrico/administração & dosagem , Nitroprussiato/administração & dosagem , Ervilhas/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Protoplastos/efeitos dos fármacos , Protoplastos/fisiologia , Espécies Reativas de Oxigênio/administração & dosagem
7.
PLoS One ; 15(1): e0227654, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929590

RESUMO

Tuberculoid leprosy (TT) is characterized by cutaneous lesions called plaques. Although microvascular ultrastructure of TT patients' skin is well-documented, little is known about functional aspects of their microcirculation. We aimed, for the first time, to evaluate, in vivo, the microcirculation of TT cutaneous lesions. Seven TT patients, males, under treatment were included in the study. The spectral analysis of frequency components of flowmotion (endothelial, sympathetic, myogenic, cardiac and respiratory) was performed using laser Doppler flowmetry (LDF). Endothelial dependent and independent vasodilatations were assessed by LDF associated to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, respectively. Vessel density (VD), perfused vessel density (PVD), proportion of perfused vessels (PPV%), microvascular flow index (MFI) and flow heterogeneity index (FHI), reflecting tissue perfusion and oxygenation, were evaluated through sidestream dark field (SDF) imaging. All microvascular analysis were performed in TT lesions and in healthy skin in the contralateral limb of the same patient, used as control skin. VD, PVD and PPV% and MFI were significantly lower in the cutaneous lesion compared to contralateral healthy skin. The contribution of different frequency components of flowmotion, endothelial dependent and independent vasodilatations and FHI were not statistically different between control skin and cutaneous lesion. Our results suggest that TT cutaneous lesions have a significant impairment of tissue perfusion, which may aggravate peripheral nerve degeneration caused by Mycobacterium leprae infection.


Assuntos
Hanseníase Tuberculoide/diagnóstico por imagem , Microcirculação , Microvasos/diagnóstico por imagem , Pele/diagnóstico por imagem , Acetilcolina/metabolismo , Adulto , Estudos Transversais , Humanos , Hanseníase Tuberculoide/fisiopatologia , Hanseníase Tuberculoide/terapia , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Nitroprussiato/metabolismo , Pele/irrigação sanguínea , Pele/fisiopatologia , Adulto Jovem
8.
Physiol Plant ; 168(2): 361-373, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31433490

RESUMO

Sodium nitroprusside (SNP) and hydrogen peroxide (H2 O2 ), as priming agents, have the well-recorded property to increase plant tolerance against a range of different abiotic stresses such as salinity. In this regard, the present study was conducted to evaluate the effect of different levels of SNP (100 and 200 µM) and H2 O2 (2.5 and 5 mM) as well as their combinations under salt stress (0 and 50 mM NaCl) on key physiological and biochemical attributes of the economically important aromatic plant basil (Ocimum basilicum L.) grown under hydroponic culture. Results revealed that morphological parameters such as plant height, root length, leaf fresh and dry weights (FW and DW) were significantly decreased by salinity stress, while SNP and H2 O2 treatments, alone or combined, increased FW and DW thus enhancing plant tolerance to salt stress. Furthermore, 200 µM SNP + 2.5 mM H2 O2 appeared to be the most effective treatment by causing significant increase in chlorophyll a and b, anthocyanin content and guaiacol peroxidase and ascorbate peroxidase enzymes activities under saline condition. In addition, analytical measurements showed that essential oil profile (concentration of main components) under salt stress was mostly affected by SNP and H2 O2 treatments. The highest increase was observed for methyl chavicol (43.09-69.91%), linalool (4.8-17.9%), cadinol (1.5-3.2%) and epi-α-cadinol (0.18-10.75%) compounds. In conclusion, current findings demonstrated a positive crosstalk between SNP and H2 O2 toward improved basil plant tolerance to salt stress, linked with regulation of essential oil composition.


Assuntos
Peróxido de Hidrogênio/farmacologia , Nitroprussiato/farmacologia , Ocimum basilicum/fisiologia , Estresse Salino , Ocimum basilicum/efeitos dos fármacos , Óleos Voláteis/química , Óleos Vegetais/química , Salinidade
9.
Environ Pollut ; 257: 113540, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31708278

RESUMO

In plants, excess selenium (Se) causes toxicity, while the beneficial effects of nitric oxide (NO) have verified in plants under various abiotic conditions. In order to ensure safely Se-enriched rice production, the objective of the research was to clarify how exogenous NO alleviated high Se toxicity in rice. Under high Se (25 µM) stress, the effects of exogenous NO (by applying sodium nitroprusside, an exogenous NO donor) on growth parameters, Se content, Se speciation, photosynthesis, antioxidant system, expressions of Se transport and metabolism-related genes (phosphate transporter, OsPT2; S-adenosylmethionine synthase 1, OsSAMS1; cysteine synthase, OsCS; Se-binding protein gene, OsSBP1) in rice seedlings were investigated by a hydroponic experiment. The results showed that exogenous NO alleviated high Se-induced irreversible damage to root morphology, growth, photosynthesis, antioxidant capacity and decreased the contents of MDA, H2O2 and proline significantly in rice seedlings. Compared with high Se treatment, application of exogenous NO reduced root Se content (10%), and the Se(VI) decreased by 100% in root and shoot. Besides, exogenous NO decreased the accumulation of inorganic Se speciation in rice roots and shoots. Also, the qRT-PCR analysis showed that down-regulated gene expressions of OsPT2, OsSAMS1 and OsCS affected significantly via exogenous NO. So, the exogenous NO could effectively decrease the toxicity of high Se treatment in rice.


Assuntos
Óxido Nítrico/metabolismo , Oryza/efeitos dos fármacos , Selênio/toxicidade , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Transporte Biológico/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Hidroponia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Oryza/metabolismo , Oryza/fisiologia , Fotossíntese/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plântula/efeitos dos fármacos , Selênio/metabolismo , Poluentes do Solo/metabolismo
10.
Chemosphere ; 244: 125480, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31821927

RESUMO

The present study was conducted to evaluate the effect of arsenic (As) toxicity and the mitigating role of nitric oxide (NO) donor sodium nitroprusside (SNP) on Vicia faba. Arsenics stress decreased the growth and biomass yield, and photosynthetic pigments, but it enhanced As accumulation. Supplementation of NO enhanced the afore-mentioned parameters except As accumulation which decreased in both shoot and root. Supplementation of NO enhanced the shoot tolerance index (Shoot TI%), root tolerance index (Root TI%) but it declined the As translocation factor (TF). Application of NO alleviated the As-induced decline in net assimilation rate, stomatal conductance, transpiration and leaf relative water content. The levels of proline and glycine betaine (GB) further increased due to NO application, whereas malondialdehyde (MDA), hydrogen peroxide (H2O2), electrolyte leakage (EL) and methylglyoxal (MG) declined considerably. Activities of enzymatic antioxidants such as superoxide dismutase (SOD) and catalase (CAT) increased under As stress. Supplementation of NO up-regulated the enzymes involved in Asc-Glu cycle and glyoxalase cycle under As toxicity. Another experiment was setup to authenticate whether NO was certainly able to alleviate As toxicity. For this purpose, the NO scavenger [2-(4-carboxy-2 phenyl)-4,4,5,5-tertamethylimidazoline-1-oxyl-3-oxide (cPTIO)] was added to As and NO supplemented plants. Addition of cPTIO to NO supplemented As-treated plants showed the same effect when As alone was supplied to plants. In conclusion, addition of NO to the growth medium maintained the plant performance under As toxicity through modulation of physio-biochemical attributes, antioxidant enzymes, and the Asc-Glu and glyoxalase systems.


Assuntos
Antioxidantes/metabolismo , Arsênico/toxicidade , Nitroprussiato/metabolismo , Poluentes do Solo/toxicidade , Vicia faba/fisiologia , Metabolismo dos Carboidratos/efeitos dos fármacos , Catalase/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio , Lactoilglutationa Liase/metabolismo , Malondialdeído , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo , Plântula/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Vicia faba/metabolismo
11.
Physiol Plant ; 168(3): 576-589, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31102278

RESUMO

A variety of cellular responses is needed to ensure the plants survival during drought, but little is known about the signaling mechanisms involved in this process. Soybean cultivars (EMBRAPA 48 and BR 16, tolerant and sensitive to drought, respectively) were exposed to the following treatments: control conditions (plants in field capacity), drought (20% of available water in the soil), sodium nitroprusside (SNP) treatment (plants irrigated and treated with 100-µM SNP [SNP-nitric oxide (NO) donor molecule], and Drought + SNP (plants subjected to drought and SNP treatment). Plants remained in these conditions until the reproductive stage and were evaluated for physiological (photosynthetic pigments, chlorophyll a fluorescence and gas exchange rates), hydraulic (water potential, osmotic potential and leaf hydraulic conductivity) and morpho-anatomical traits (biomass, venation density and stomatal characterization). Exposure to water deficit considerably reduced water potential in both cultivars and resulted in decrease in photosynthesis and biomass accumulation. The addition of the NO donor attenuated these damaging effects of water deficit and increased the tolerance index of both cultivars. The results showed that NO was able to reduce plant's water loss, while maintaining their biomass production through alteration in stomatal characteristics, hydraulic conductivity and the biomass distribution pattern. These hydraulic and morpho-anatomical alterations allowed the plants to obtain, transport and lose less water to the atmosphere, even in water deficit conditions.


Assuntos
Secas , Óxido Nítrico/fisiologia , Soja/fisiologia , Estresse Fisiológico , Água , Clorofila A , Nitroprussiato/farmacologia , Fotossíntese , Folhas de Planta/fisiologia
12.
Am J Physiol Regul Integr Comp Physiol ; 318(1): R148-R155, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577152

RESUMO

Despite remission of clinical symptoms postpartum, women who have had preeclampsia demonstrate microvascular endothelial dysfunction, mediated in part by increased sensitivity to angiotensin II (ANG II). Angiotensin-(1-7) [Ang-(1-7)] is an endogenous inhibitor of the actions of ANG II and plausible druggable target in women who had preeclampsia. We therefore examined the therapeutic potential of Ang-(1-7) in the microvasculature of women with a history of preeclampsia (PrEC; n = 13) and parity-matched healthy control women (HC; n = 13) hypothesizing that administration of Ang-(1-7) would increase endothelium-dependent dilation and nitric oxide (NO)-dependent dilation and decrease ANG II-mediated constriction in PrEC. Using the cutaneous microcirculation, we assessed endothelium-dependent vasodilator function in response to graded infusion of acetylcholine (ACh; 10-7 to 102 mmol/L) in control sites and sites treated with 15 mmol/L NG-nitro-l-arginine methyl ester (l-NAME; NO-synthase inhibitor), 100 µmol/L Ang-(1-7), or 15 mmol/L l-NAME + 100 µmol/L Ang-(1-7). Vasoconstrictor function was measured in response to ANG II (10-20-10-4 mol/L) in control sites and sites treated with 100 µmol/L Ang-(1-7). PrEC had reduced endothelium-dependent dilation (P < 0.001) and NO-dependent dilation (P = 0.04 vs. HC). Ang-(1-7) coinfusion augmented endothelium-dependent dilation (P < 0.01) and NO-dependent dilation (P = 0.03) in PrEC but had no effect in HC. PrEC demonstrated augmented vasoconstrictor responses to ANG II (P < 0.01 vs. HC), which was attenuated by coinfusion of Ang-(1-7) (P < 0.001). Ang-(1-7) increased endothelium-dependent vasodilation via NO synthase-mediated pathways and attenuated ANG II-mediated constriction in women who have had preeclampsia, suggesting that Ang-(1-7) may be a viable therapeutic target for improved microvascular function in women who have had a preeclamptic pregnancy.


Assuntos
Angiotensina I/farmacologia , Endotélio Vascular/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Pré-Eclâmpsia , Acetilcolina/farmacologia , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Nitroprussiato/farmacologia , Gravidez
13.
Chemosphere ; 239: 124523, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31499308

RESUMO

Arsenic (As) is a toxic metalloid that severely hampers plant growth and also poses health risks for humans through the food chain. Although nitric oxide (NO) is known to improve plant resistance to multiple stresses including metal toxicity, little is known about its role in the As tolerance of hyperaccumulator plants. This study investigates the role of the exogenously applied NO donor, sodium nitroprusside (SNP), in improving the As tolerance of Isatis cappadocica, which has been reported to hyperaccumulate As. Exposure to toxic As concentrations significantly increases NO production and damages the cell membrane, as indicated by increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, thereby reducing plant growth. However, the addition of SNP improves growth and alleviates As-induced oxidative stress by enhancing the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione S-transferase (GST), glutathione (GSH), as well as proline and thiol concentrations, thereby confirming the beneficial role played by NO in increasing As stress tolerance. Furthermore, the As-induced decrease in growth and the increase in oxidative stress were more marked in the presence of bovine hemoglobin (Hb; a NO scavenger) and N(G)-nitro-l-arginine methyl ester (l-NAME; a NO synthase inhibitor), thus demonstrating the protective role of NO against As toxicity. The reduction in NO concentrations by l-NAME suggests that NOS-like activity is involved in the generation of NO in response to As in I. cappadocica.


Assuntos
Antioxidantes/metabolismo , Arsênico/toxicidade , Isatis/efeitos dos fármacos , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Animais , Ascorbato Peroxidases/metabolismo , Bovinos , Membrana Celular/patologia , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Peróxido de Hidrogênio/metabolismo , Isatis/metabolismo , Malondialdeído/metabolismo , Doadores de Óxido Nítrico , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
14.
Bioelectrochemistry ; 132: 107441, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31869701

RESUMO

Sodium nitroprusside (SNP) is a nitric oxide (NO)-donor drug used clinically to treat severe hypertension, however, there are limitations associated with its mechanism of action that prevent widespread adoption. In particular, its impact on cerebral hemodynamics is controversial and direct evidence on its effects are lacking. Electrochemical methods provide an attractive option to undertake real time neurochemical measurements in situ using selective microsensors. Herein, we report the novel application of an existing platinum (Pt)-Nafion® sensor to measure the release of NO from SNP under in vitro and in vivo conditions. Initially, the temporal release of NO was measured and the effect of the reducing agent, ascorbic acid (AA), was elucidated in vitro. A combined microdialysis/NO sensor construct was implanted into the striatum of anaesthetised mice and the local perfusion of 10 mM SNP with/without AA resulted in increased NO concentration detected using the Pt-Nafion® sensor. Subsequently, the NO sensor, coupled with carbon paste electrodes (CPEs) for the electrochemical measurement of O2, were applied to investigate SNP effects in freely moving mice. A complex mechanism of action was identified that infers NO inhibition and biphasic O2 dynamics. The preliminary findings within support a strong cerebrovascular effect of systemic SNP administration that warrants careful consideration for clinical use.


Assuntos
Encéfalo/metabolismo , Técnicas Eletroquímicas/métodos , Líquido Extracelular/metabolismo , Nitroprussiato/administração & dosagem , Animais , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Óxido Nítrico/metabolismo , Oxigênio/metabolismo
15.
Int J Mol Sci ; 20(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752185

RESUMO

Cadmium (Cd) is one of the prominent environmental hazards, affecting plant productivity and posing human health risks worldwide. Although salicylic acid (SA) and nitric oxide (NO) are known to have stress mitigating roles, little was explored on how they work together against Cd-toxicity in rice. This study evaluated the individual and combined effects of SA and sodium nitroprusside (SNP), a precursor of NO, on Cd-stress tolerance in rice. Results revealed that Cd at toxic concentrations caused rice biomass reduction, which was linked to enhanced accumulation of Cd in roots and leaves, reduced photosynthetic pigment contents, and decreased leaf water status. Cd also potentiated its phytotoxicity by triggering reactive oxygen species (ROS) generation and depleting several non-enzymatic and enzymatic components in rice leaves. In contrast, SA and/or SNP supplementation with Cd resulted in growth recovery, as evidenced by greater biomass content, improved leaf water content, and protection of photosynthetic pigments. These signaling molecules were particularly effective in restricting Cd uptake and accumulation, with the highest effect being observed in "SA + SNP + Cd" plants. SA and/or SNP alleviated Cd-induced oxidative damage by reducing ROS accumulation and malondialdehyde production through the maintenance of ascorbate and glutathione levels, and redox status, as well as the better activities of antioxidant enzymes superoxide dismutase, catalase, glutathione S-transferase, and monodehydroascorbate reductase. Combined effects of SA and SNP were observed to be more prominent in Cd-stress mitigation than the individual effects of SA followed by that of SNP, suggesting that SA and NO in combination more efficiently boosted physiological and biochemical responses to alleviate Cd-toxicity than either SA or NO alone. This finding signifies a cooperative action of SA and NO in mitigating Cd-induced adverse effects in rice, and perhaps in other crop plants.


Assuntos
Cádmio/toxicidade , Nitroprussiato/farmacologia , Oryza/crescimento & desenvolvimento , Ácido Salicílico/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Sinergismo Farmacológico , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Oryza/efeitos dos fármacos , Oryza/metabolismo , Fotossíntese , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Água/metabolismo
16.
Invest Ophthalmol Vis Sci ; 60(12): 4002-4007, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31560766

RESUMO

Purpose: This study aims to investigate the pharmacologic consequence of genetic deletion of nitric oxide synthase 3 (NOS3) in caveolin 1 (Cav1)-/- mice (double knockout [DKO]) in response to a nitric oxide (NO) donor and two NOS inhibitors. Methods: NO donor sodium nitroprusside (SNP; 10-40 mg/mL), NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME; 10-200 µM), and cavtratin (10-75 µM ) was administered topically to the eye while the contralateral eyes were vehicle controls. Intraocular pressure (IOP) was measured in both eyes by tonometry. Cyclic guanosine monophosphate (cGMP) level in outflow tissue was measured by ELISA assay. Protein expression were analyzed by western blot. Results: Inducible NOS (iNOS) expression significantly increased in the DKO mice compared with the wild type (WT), Cav1 knockout (Cav1 KO), and NOS3 KO mice. In contrast to WT, Cav1 KO and NOS3 KO mice, SNP concentration of up to 30 mg/mL did not significantly affect IOP in DKO mice. However, higher concentration (40 mg/mL) SNP significantly reduced IOP by 14% (n = 8, P < 0.01). Similarly, only 200 µM L-NAME produced a significant increase in IOP (n = 10, P < 0.05). Cavtratin did not significantly change IOP in DKO and NOS3 KO mice. cGMP activity in DKO mice was significantly lower than Cav1 KO mice (n = 4, P < 0.05). Conclusions: In conclusion, our results demonstrated that genetic deletion of NOS3 in Cav1 deficient mice resulted in reduced sensitivity to the NO donor SNP and the two NOS inhibitors possibly due to compromised NOS and cGMP activity.


Assuntos
Caveolina 1/deficiência , Inibidores Enzimáticos/farmacologia , Deleção de Genes , Pressão Intraocular/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo III/genética , Administração Oftálmica , Animais , Western Blotting , Caveolina 1/metabolismo , Caveolina 1/farmacologia , GMP Cíclico/metabolismo , Ensaio de Imunoadsorção Enzimática , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Nitroprussiato/farmacologia , Fragmentos de Peptídeos/farmacologia , Tonometria Ocular
17.
Cell Biochem Funct ; 37(7): 545-552, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429100

RESUMO

Ras-GTPases regulate many central signalling pathways in the cell. Hypoxia induces nitrosative/oxidative stress and dysregulates Ras-dependent downstream processes. H-Ras possesses two cysteine residues (C181 and C184) in the C-termini, which are palmitoylated once or twice. Palmitoylation is sufficient for promoting stable plasma membrane localization. We hypothesized that high concentrations of hypoxia-formed nitric oxide could induce terminal cysteine S-nitrosylation, followed by depalmitoylation and H-Ras mislocalization. We investigated the action of a 100-µM nitric oxide-donor (sodium nitroprusside [SNP]) and a 100-µM palmitoylation inhibitor (2-bromopalmitate) on the distribution of membrane-bound S-nitrosylated and palmitoylated H-Ras under hypoxic/normoxic conditions in undifferentiated/differentiated pheochromocytoma (PC12) cells. We found that under normoxic conditions, SNP increases membrane-bound H-Ras nitrosylation only in differentiated cells, whereas under hypoxic conditions, SNP stimulates H-Ras nitrosylation in both differentiated and undifferentiated cells. SNP greatly decreases the palmitoylation of H-Ras under hypoxic conditions in both undifferentiated and differentiated cells, while under normoxic conditions, the effect of SNP is more negligible. Furthermore, Western blot analyses have shown that SNP decreases ERK phosphorylation under hypoxic conditions, in parallel with an elevation in hypoxia-induced factor activity and intracellular succinate concentration. We propose that high concentrations of hypoxia-formed nitric oxide can nitrosylate H-Ras terminal cysteines, which induce H-Ras activity dysregulation and alter the cellular response to hypoxia. SIGNIFICANCE OF THE STUDY: To our knowledge, these observations may be important for cancer prevention and therapy because cancer is one of the most prevalent disorders caused by the misregulation of Ras activity by a redox agent. Oncogenic activation of the H-Ras gene has been found in a wide variety of neoplastic transformations, and thus, investigation of the redox regulation of H-Ras activity is significant for cancer research as well.


Assuntos
Diferenciação Celular , Hipóxia/tratamento farmacológico , Nitroprussiato/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Animais , Diferenciação Celular/efeitos dos fármacos , Hipóxia/metabolismo , Células PC12 , Proteínas Proto-Oncogênicas p21(ras)/análise , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ratos
18.
PLoS One ; 14(8): e0221642, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31454379

RESUMO

Biological rhythms regulate innumerable physiological processes, yet little is known of factors that regulate many of these rhythms. Disruption in the timing of these rhythms can have devastating impacts on population sustainability. We hypothesized that the timing of the molt infradian rhythm in the crustacean Daphnia magna is regulated by the joint action of the protein E75 and nitric oxide. Further, we hypothesized that disruption of the function of E75 would adversely impact several physiological processes related to growth and reproduction. Analysis of mRNA levels of several genes, involved in regulating the molt cycle in insects, revealed the sequential accumulation of E75, its dimer partner HR3, FTZ-F1, and CYP18a1 during the molt cycle. Exposure to the nitric oxide donor sodium nitroprusside early in the molt cycle had no effect on E75 or HR3 mRNA levels, but delayed the peak accumulation of FTZ-F1 and CYP18a1 mRNA. The subsequent exuviation was also delayed consistent with the delay in peak accumulation of FTZ-F1 and CYP18a1. These results supported our assertion that nitric oxide binds E75 rendering it incapable of binding HR3. Excess HR3 protein then enhanced the accumulation of the downstream products FTZ-F1 and CYP18a1. Similarly, suppression of E75 mRNA levels, using siRNA, had no effect on mRNA levels of HR3 but elevated mRNA levels of FTZ-F1. Consistent with these molecular responses, the suppression of E75 using siRNA increased the duration of the molt cycle and reduced the number of offspring produced. We conclude that the molt cycle of daphnids is regulated in a manner similar to insects and disruption of E75 results in a lengthening of the molt cycle and a reduction the release of viable offspring.


Assuntos
Daphnia/metabolismo , Daphnia/fisiologia , Muda/fisiologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Daphnia/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Modelos Biológicos , Muda/efeitos dos fármacos , Muda/genética , Nitroprussiato/farmacologia , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Int J Neurosci ; 129(12): 1155-1165, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31256739

RESUMO

Aim of the study: The current study was aimed to investigate the neuropathic pain attenuating mechanism of pregabalin using chronic constriction injury (CCI) model in rats. Material and Methods: The sciatic nerve was ligated by placing four loose ligatures around it to induce neuropathic pain. The pain development in terms of cold allodynia, mechanical hyperalgesia, and heat hyperalgesia was assessed on the 7th and 14th day after surgery, using acetone drop, pinprick, and hot plate tests. On the 14th day after the injury, pain parameters were assessed 30 minutes after administration of pregabalin (30 mg/kg) and sodium nitroprusside (5 mg/kg) in CCI-subjected rats. Results: CCI led to induction of neuropathic pain, which was more prominent on 14th day in comparison to 7th day. A single administration of pregabalin and sodium nitroprusside on 14th day, markedly reduced pain parameters and increased serum nitrite levels. Pretreatment with L-NAME abolished neuropathic pain attenuating effects of pregabalin suggesting that pregabalin may increase the levels of nitric oxide to mitigate neuropathic pain. Pretreatment with naloxone significantly abrogated pain attenuating effects of pregabalin and sodium nitroprusside in CCI-subjected rats suggesting that pregabalin and nitric oxide-mediated analgesic action are mediated through release of endogenous opioids. Moreover, naloxone failed to modulate pregabalin-induced increase in nitric oxide levels suggesting that the opioid system does not control the nitric oxide levels, and opioids may be downstream modulators of nitric oxide. Conclusion: Pregabalin may increase the release of nitric oxide, which may increase the release of endogenous opioids to attenuate neuropathic pain in CCI subjected rats.


Assuntos
Analgésicos/administração & dosagem , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Pregabalina/administração & dosagem , Animais , Modelos Animais de Doenças , Hiperalgesia/etiologia , Neuralgia/etiologia , Nitroprussiato/administração & dosagem , Medição da Dor , Ratos Wistar
20.
Planta ; 250(5): 1475-1489, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31327043

RESUMO

MAIN CONCLUSION: Nitric oxide increased lettuce's tolerance to salinity by restoring its hormonal balance, consequently reducing Na + accumulation and activating defense mechanisms that allowed the attenuation of ionic, oxidative, and osmotic stresses. Agricultural crops are continually threatened by soil salinity. The plant's ability to tolerate soil salinity can be increased by treatment with the signaling molecule nitric oxide (NO). Involvement of NO in plant metabolism and its interactions with phytohormones have not been fully described, so knowledge about the role of this radical in signaling pathways remains fragmented. In this work, Lactuca sativa (lettuce) plants were subjected to four treatments: (1) control (nutrient solution); (2) SNP [nutrient solution containing 70 µM sodium nitroprusside (SNP), an NO donor]; (3) NaCl (nutrient solution containing 80 mM NaCl); or (4) SNP + NaCl (nutrient solution containing SNP and NaCl). The plants were exposed to these conditions for 24 h, and then, the roots and leaves were collected and used to evaluate biochemical parameters (reactive oxygen species (ROS) production, cell membrane damage, cell death, antioxidant enzymes activities, and proline concentration), physiological parameters (pigments' concentration and gas-exchange measurements), and phytohormone content. To evaluate growth, tolerance index, and nutrient concentration, the plants were exposed to the treatments for 3 days. L sativa exposure to NaCl triggered ionic, osmotic, and oxidative stress, which resulted in hormone imbalance, cell death, and decreased growth. These deleterious changes were correlated with Na+ content in the vegetative tissues. Adding NO decreased Na+ accumulation and stabilized the mineral nutrient concentration, which maintained the photosynthetic rate and re-established growth. NO-signaling action also re-established the phytohormones balance and resulted in antioxidant system activation and osmotic regulation, with consequent increase in plants tolerance to the salt.


Assuntos
Alface/fisiologia , Óxido Nítrico/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Transdução de Sinais , Cloreto de Sódio/efeitos adversos , Clorofila/metabolismo , Ácidos Indolacéticos/metabolismo , Alface/crescimento & desenvolvimento , Nitroprussiato/metabolismo , Pressão Osmótica , Estresse Oxidativo , Fotossíntese/efeitos dos fármacos , Salinidade , Sódio/metabolismo , Estresse Fisiológico
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