Search Results (196)

Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate analyzer (Roche), which is based on multiple electrode impedance aggregometry. Platelet aggregation was induced using adenosine diphosphate (ADP), and the area under the curve (AUC) served as the primary endpoint. In addition, platelet counts and C-reactive protein (CRP) levels were measured. To further evaluate nitric oxide (NO)-mediated inhibition of platelet aggregation, blood samples were incubated with the NO donor, sodium nitroprusside (SNP), and the phosphodiesterase 5A (PDE5A) inhibitor, sildenafil. Results: A total of 60 patients undergoing HD and 67 healthy controls were included in the analysis. Patients receiving HD treatment had significantly lower platelet counts compared to healthy controls (226.9 ± 53.47 vs. 246.7 ± 47.21 G/L, p = 0.029). Platelet aggregation was markedly reduced in patients undergoing HD compared to controls (462.0 ± 266.54 vs. 644.5 ± 254.44 AU × min, p < 0.001) with a significant correlation for platelet count (r = 0.42, p = 0.001) and systemic inflammation as indicated by CRP levels (r = 0.28, p = 0.035). Following SNP and sildenafil administration, inhibition of platelet aggregation remained more pronounced in patients undergoing HD. However, the change in platelet aggregation after SNP/sildenafil treatment did not differ significantly between the groups. Conclusions: Patients undergoing HD exhibit altered platelet function, indicated by reduced aggregation and platelet counts, as well as an association with systemic inflammation. Multiple electrode impedance aggregometry appears to be a feasible method for detecting platelet function alterations in patients receiving HD treatment. Responsiveness to NO donors was preserved in patients undergoing HD. Further studies are needed to identify the underlying mechanisms, particularly the role of NO signaling in platelet dysfunction in patients undergoing HD. Full article

Cold storage is widely used for the postharvest preservation of fruits and vegetables; however, okra, as a tropical vegetable, is susceptible to chilling injury under low-temperature storage conditions, leading to quality deterioration, reduced nutritional value, and significant economic losses. Nitric oxide (NO), as an important signaling molecule, plays a crucial role in the postharvest preservation of fruits and vegetables. To investigate the effects of different concentrations of nitric oxide on the postharvest quality of okra under cold storage, fresh okra pods were treated with sodium nitroprusside (SNP), a commonly used NO donor, at concentrations of 0 (control), 0.5 (T1), 1.0 (T2), 1.5 (T3), and 2.0 mmol·L⁻¹ (T4). The results showed that low-concentration NO treatment (T1) significantly reduced weight loss, improved texture attributes including hardness, springiness, chewiness, resilience, and cohesiveness, and suppressed the increase in adhesiveness. T1 treatment also effectively inhibited excessive accumulation of cellulose and lignin, thereby maintaining tissue palatability and structural integrity. Additionally, T1 significantly delayed chlorophyll degradation, preserved higher levels of soluble sugars and proteins, and enhanced the activities of key antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), contributing to improved oxidative stress resistance and membrane stability. In contrast, high-concentration NO treatments (T3 and T4) led to pronounced quality deterioration, characterized by accelerated membrane lipid peroxidation as evidenced by increased malondialdehyde (MDA) content and relative conductivity, and impaired antioxidant defense, resulting in rapid texture degradation, chlorophyll loss, nutrient depletion, and oxidative damage. These findings provide theoretical insights and practical guidance for the precise application of NO in extending shelf life and maintaining the postharvest quality of okra fruits. Full article

Germination ability and seedling development of grape (Vitis vinifera L.) seeds show significant differences depending on cultivar characteristics and germination conditions, and this situation is known to create significant difficulties in grape breeding programs and vegetative propagation. In this study, we explored the effects of different concentrations of sodium nitroprusside (SNP; 500–3000 ppm) and gibberellic acid (GA₃) on seed germination and seedling growth in several grape cultivars. Our findings show that cultivar, treatment type, and their interaction had significant effects on both germination and growth. The 5 BB rootstock stood out with consistently high germination rates, reaching up to 95% with 1500 ppm SNP. Overall, SNP treatments outperformed both the control and GA₃ applications, although the most effective concentration differed by cultivar. The most beneficial SNP doses ranged between 1000 and 3000 ppm, with 1500 ppm yielding the highest improvement, up to a 21.6% increase compared to the control. Notably, the ‘Çeliksu’ cultivar responded strongly to SNP, while ‘Rizpem’ showed weak germination, regardless of treatment. Seedling growth, as measured by plant height and node number, was also influenced by both treatment and cultivar, with 5 BB again showing the most robust development. Multivariate analyses revealed strong correlations across germination dates and growth traits. Higher SNP concentrations (1500–3000 ppm) consistently promoted better germination and seedling vigor than GA₃ and untreated controls. These results highlight the importance of considering cultivar-specific responses and suggest that well-calibrated SNP applications could be a valuable tool for improving seed-based propagation in grape breeding programs. Full article

The enzyme transglutaminase 2 (TG2) has an open conformation with transamidase activity which crosslinks matrix proteins contributing to fibrosis development. LDN-27219 promotes the closed conformation of TG2, which can enhance vasodilation, but its effects in renal tissue are unknown. We investigated whether LDN-27219 treatment affects albuminuria and markers of renal fibrosis as well as ex vivo vasodilatation. Male C57BL/6 mice (n = 48) underwent unilateral nephrectomy plus insertion of a deoxycorticosterone acetate pellet (DOCA group) or nephrectomy only (sham group). Both groups were randomized to intraperitoneal treatment with either LDN-27219 (8 mg/kg twice daily) or vehicle for 2 weeks. Urine albumin excretion was evaluated by metabolic cages. Kidney tissue fibrosis markers were assessed by qPCR and Western blotting, while the TG2 conformational state was evaluated using native gel electrophoresis. Collagen staining was performed using Picrosirius red and quantified under circularly polarized light. Mesenteric arteries were mounted in wire myographs for evaluation of vasorelaxation. DOCA mouse developed significant albuminuria (p < 0.001 vs. sham), but neither TG2 mRNA nor protein expression was upregulated in the kidney. However, the relative amount of TG2 in the closed conformation was higher in DOCA mice. LDN-27219 did not affect albuminuria, but LDN-27219-treated DOCA mice showed less urine production and less collagen staining than vehicle-treated DOCA mice. LDN-27219 did not affect TG2 mRNA or TG2 protein expression or mRNA of fibrosis markers. LDN-27219-treated mice had enhanced vasorelaxation to the nitric oxide donor sodium nitroprusside. In conclusion, LDN-27219 treatment in the one-kidney DOCA–salt model did not affect renal TG2 mRNA and protein expression or albuminuria but still exerted beneficial effects in terms of reduced kidney fibrosis and urine production in addition to enhanced vasodilatation. Full article

The present research was designed to assess the potential effect of SNP to alleviate salinity stress injury in fig transplants cv. Conadria. One-year-old transplants irrigated with saline water (6.25 ds/m) were treated with sodium nitroprusside (SNP) at four concentrations (0, 50, 100 and 200 µM); untreated transplants exposed to salt stress represent the positive control, while the non-stressed transplants represent the negative control. Salt stress showed a considerable increase in lipid peroxidation, proline, sodium, chloride content and antioxidant enzyme activity and reduced vegetative growth parameters, photosynthetic pigments, phenolic content and K/Na ratio. SNP reduced salt stress injury in fig transplants through maintaining higher values of growth parameters and photosynthetic pigment content, reducing sodium accumulation and maintaining the integrity of cell membrane lipids. SNP-treated transplants accumulated higher amounts of potassium ions and a higher K/Na ratio. SNP at 100 µM was the most efficient treatment in enhancing the response to salt stress. Overall, the results show that SNP application is a promising practice for alleviating salt stress on fig transplants. Full article

Triterpenoids are the bioactive components in Inonotus obliquus with extensive medicinal prospects, but their low content in fermentation production is the main limiting factor for their application. This study focuses on nitric oxide (NO), an important signaling molecule within organisms, aiming to explore its inducing effect on the synthesis of triterpenes in I. obliquus and the potential signaling transduction mechanisms involved. Compared with the control group, the content of representative triterpenoid betulin increased by 70.59% after adding the NO donor sodium nitroprusside. Gene expression level detection revealed that NO mainly promotes its biosynthesis by activating the transcription of key enzyme genes in the downstream pathway of betulin biosynthesis, thereby increasing its abundance. Tracing upstream, the NO signal was found to induce the upregulation of genes related to cellular antioxidant and calcium ion signaling pathways. Notably, IoCAMP responded strongly to the NO signal, participating in the regulation of cytoplasmic Ca²⁺ concentration by altering the Ca²⁺ concentration of mitochondria together with IoCATP and IoCALM. Additionally, the signaling of changes in Ca²⁺ concentrations is likely to crosstalk with the reactive oxygen species (ROS) signaling pathway. The increase in enzyme activity of IoNOX after NO induction confirmed the activation of the ROS signaling pathway. It works in synergy with IoSOD and IoCAT to reduce oxidative damage and promote downstream triterpenoid biosynthesis. This study not only contributes to clarify the signaling pathways regulating NO-mediated triterpenoid biosynthesis but also provides a theoretical basis for the efficient production of triterpenoid active components in I. obliquus. Full article

Bisphenol A (BPA) is the most used widely synthetic compound for the manufacture of polycarbonate plastics and epoxy resins produced worldwide. Given its androgenic and estrogenic activities, BPA is an endocrine disruptor that is linked to neurological and vascular outcomes, including strokes. Therefore, this study aims to investigate the mechanisms by which a 24 h exposure to BPA (0.002–20 μM) modifies the contractile function of rat middle cerebral artery (MCA) smooth muscle cells (SMCs). Thus, MCA explants were isolated from Wistar rats, and the SMC-MCA vasoactive response was assessed using planar cell surface area, while the gene expression of proteins and ion channel subunits involved in the MCA vasoactive response was evaluated by real-time quantitative PCR. The exposure to BPA (0.02 and 2 μM) decreased the noradrenaline (NA) vasocontractile response and sodium nitroprusside (SNP) vasorelaxant response. Moreover, exposure to BPA (0.02 and 2 μM) increased the gene expression of the soluble guanyl cyclase protein and the large conductance Ca²⁺-activated K⁺ channels (1.1 α-subunit). These results suggest an impairment of the SMC-MCA vasoactive response induced by intermediate BPA concentrations, an effect not attained for the lowest or highest exposure concentrations (non-monotonic inverted U-shaped response). In summary, these findings suggest that BPA exposure modifies MCA vascular homeostasis by interfering with the nitric oxide (NO) pathway and may, thus, be involved in ischemic stroke development. Full article

Drug-eluting stents, which release antiproliferative agents such as sirolimus and everolimus, were developed to reduce the risk of restenosis associated with bare-metal stents. However, despite their proven clinical efficacy, concerns remain regarding in-stent restenosis due to delayed endothelial healing and the risk of late thrombotic events. In this study, we aimed to determine the vascular effects of sirolimus and everolimus on isolated human saphenous vein (SV) samples obtained from patients undergoing coronary artery bypass surgery. SV rings were subjected to sirolimus and everolimus in acute and pretreatment conditions in vitro. Increasing concentrations of sirolimus (10⁻⁸–10⁻⁵ M), everolimus (10⁻⁸–10⁻⁵ M), and their vehicle were administered to SV rings precontracted with phenylephrine (Phe,10⁻⁶–5 × 10⁻⁶ M) to evaluate their direct vascular effects. Additionally, SV rings were incubated (16 h) either with sirolimus (10⁻⁵ M), everolimus (10⁻⁶ M), or the vehicle. Thereafter, the contractile responses to Phe (10⁻⁸–10⁻⁴ M), and the endothelium-dependent and endothelium-independent relaxant responses to acetylcholine (ACh, 10⁻⁸–10⁻⁴ M) and sodium nitroprusside (SNP,10⁻⁸–10⁻⁴ M) were determined, respectively. Our findings demonstrated that sirolimus and everolimus did not exert direct relaxant and modulatory effects on vascular function in isolated human SVs. Hence, the preservation of contractile and relaxant responses with sirolimus and everolimus may have clinical implications in the context of DES implantation. Full article

Arterial and venous graft spasm can occur during harvesting or immediately after coronary artery bypass grafting (CABG), leading to increased perioperative morbidity and affecting graft patency rates. Bypass grafts harvested from diabetic patients are particularly prone to spasm. This study aimed to elucidate the functional characteristics of human bypass grafts for the internal mammary artery (IMA) and saphenous vein (SV), from both diabetic and non-diabetic patients, and to determine how diabetes affected their responses to spasmogenic and relaxant agents. SV and IMA graft rings isolated from diabetic and non-diabetic patients during CABG were placed in an isolated organ bath system. Contractions to potassium chloride (10–100 mM) and phenylephrine (10⁻⁸–10⁻⁴ M) were evaluated, and relaxation responses to acetylcholine (10⁻⁹–10⁻⁴ M) and sodium nitroprusside (10⁻⁸–10⁻⁴ M) were assessed to evaluate endothelial and smooth muscle function, respectively. We observed increased responses to phenylephrine, an alpha-1 adrenoceptor agonist, in both IMAs and SVs, as well as an increased responses to potassium chloride, a non-receptor agonist, in SVs in diabetic patients compared to non-diabetic patients. We did not observe any deterioration in endothelium-dependent relaxations in either SV or IMA grafts under diabetic conditions. This study is the first to demonstrate that diabetes exacerbates potassium chloride-induced contractions in human SV grafts. Understanding the differences in potassium chloride-induced contraction profiles between arterial and venous grafts is essential in optimizing graft spasm management and improving the patency rates of bypass grafts. Full article

Background/Objectives: Sepsis has been shown to depress arterial baroreceptor function, and this effect is counterbalanced by the cholinergic anti-inflammatory pathway. Considering the importance of central adenosine receptors in baroreceptor function, this study tested whether central adenosine A3 receptors (A3ARs) modulate the cholinergic-baroreflex interaction in sepsis and whether this interaction is modulated by mitogen-activated protein kinases (MAPKs) and related proinflammatory cytokines. Methods: Sepsis was induced by cecal ligation and puncture (CLP) and rats were instrumented with femoral and intracisternal (i.c.) catheters. Baroreflex sensitivity (BRS) was measured 24 h later in conscious animals using the vasoactive method, which correlates changes in blood pressure caused by i.v. phenylephrine (PE) and sodium nitroprusside (SNP) to concomitant reciprocal changes in heart rate. Results: The reduction in reflex bradycardic (BRS-PE), but not tachycardic (BRS-SNP), responses elicited by CLP was reversed by i.v. nicotine in a dose-related manner. The BRS-PE effect of nicotine was blunted following intracisternal administration of IB-MECA (A3AR agonist, 4 µg/rat). The depressant action of IB-MECA on the BRS facilitatory action of nicotine was abrogated following central inhibition of MAPK-JNK (SP 600125), PI3K (wortmannin), and TNFα (infliximab), but not MAPK-ERK (PD 98059). Additionally, the nicotine suppression of sepsis-induced upregulation of NFκB and NOX2 expression in the nucleus tractus solitarius (NTS) was negated by A3AR activation. The molecular effect of IB-MECA on NFκB expression disappeared in the presence of SP 600125, wortmannin, or infliximab. Conclusions: The central PI3K/MAPK-JNK/TNFα pathway contributes to the restraining action of A3ARs on cholinergic amelioration of sepsis-induced central neuroinflammatory responses and impairment of the baroreceptor-mediated negative chronotropism. Full article

Background/Objectives: Patients with psoriasis exhibit endothelial dysfunction (EDy), which increases their cardiovascular risk. Excessive salt intake impairs endothelium-dependent vascular reactivity. However, research on EDy in psoriasis has focused primarily on larger vessels, leaving skin microcirculation unexplored. This study aimed to investigate the effects of a low-salt diet (LS diet, ~3.75 g/day) on microvascular reactivity in patients with chronic plaque psoriasis. Methods: Laser Doppler flowmetry was used to assess skin microcirculation blood flow in response to vascular occlusion (postocclusive reactive hyperemia, PORH), acetylcholine (acetylcholine-induced dilation, AChID), sodium nitroprusside (SNP-induced dilation, SNPID), and local heating (local thermal hyperemia, LTH). Blood and 24 h urine samples were collected for biochemical and inflammatory parameters and dietary adherence monitoring. Results: The results showed significant reductions in systolic (p = 0.021) and mean arterial blood pressure (p = 0.007) after the LS diet. AChID increased by 16% (p = 0.029) regardless of blood pressure changes, especially in normolipemic, normotensive patients without excess visceral fat. Importantly, significant sex differences were observed, with significant improvement in endothelial function observed only in women (p = 0.031 vs. p = 0.477). PORH did not change significantly; however, a Fourier transformation analysis revealed that the endothelial component of the PORH was significantly improved following the LS diet protocol. The duration of psoriasis negatively correlated with changes in AChID (R = −0.46, p = 0.036) and LTH (R = −0.45, p = 0.041) after the LS diet, indicating that prolonged low-grade inflammation reduced endothelial function reversibility. Additionally, lower triglyceride, uric acid, and BMI levels were significant predictors of better endothelial function improvement following the LS diet. Conclusions: This study supports the beneficial effect of the early introduction of an LS diet in the treatment protocols for patients with psoriasis. Full article

Drought stress severely damages wheat growth and photosynthesis, and plants at the grain-filling stage are the most sensitive to drought throughout the entire period of development. Exogenous spraying of sodium nitroprusside (SNP) can alleviate the damage to wheat caused by drought stress, but the mechanism regulating the proline pathway remains unknown. Two wheat cultivars, drought-sensitive Zhoumai 18 and drought-tolerant Zhengmai 1860, were used as materials when the plants were cultivated to the grain-filling stage. The results show that under drought stress, SNP pretreatment effectively improved the physiological basis of photosynthesis and water use efficiency of the two cultivars, increased their tolerance to photosystem II (PSII) damage, and maintained a normal photosynthetic rate and yield. Drought stress induced an increase in pyrroline-5-carboxylate synthase (TaP5CS) gene transcription, and a comparatively greater increase was detected in Zhengmai 1860. When SNP treatment was applied before drought exposure, TaP5CS transcription was further enhanced. Induction of TaP5CS transcription promoted proline accumulation in response to drought stress, increased osmotic ability, and maintained the net photosynthetic rate, thereby increasing the accumulation of dry matter and yield traits. In this study, exogenous SNP regulates the transcription of genes related to the proline metabolism pathway and provides a theoretical basis for the establishment of wheat cultivation technology using SNP to resist drought stress. Full article

Myocardial ischemia-reperfusion injury increases myocardial microvascular permeability, leading to enhanced microvascular filtration and interstitial fluid accumulation that is associated with greater microvascular obstruction and inadequate myocardial perfusion. A burst of reactive oxygen species and inflammatory mediators during reperfusion causes myosin light chain kinase (MLCK)-dependent endothelial hyperpermeability, which is considered a preventable cause of reperfusion injury. In the present study, a single intravenous injection of MLCK peptide inhibitor PIK7 (2.5 mg/kg or 40 mg/kg) was found to suppress the vascular hyperpermeability caused by ischemia/reperfusion injury in an in vivo rat model. The antiedemic effect of PIK7 is transient and ceases within 90 min of reperfusion. The early no-reflow detected for the first time after 30 min ischemia in this model of myocardial infarction reduces the area accessible for PIK7. Electron microscopy has shown membrane-bound blebs of endotheliocytes, which partially or completely obturate the capillary lumen, and few capillaries with signs of intercellular gap formation in samples obtained from the center of the early no-reflow zone in control and PIK7-injected rats. Co-injection of PIK7 with NO donor sodium nitroprusside (SNP) increases blood flow in the zone of early no-reflow, while reducing the increased vascular permeability caused by SNP. Full article

The lily is a globally popular cut flower, and managing dormancy in lily bulblets is essential for continuous, year-round production. While nitric oxide (NO) has been shown to influence seed dormancy and germination, its role in dormancy release in lilies was previously unconfirmed. In this study, we investigated the effects of NO on dormancy release in lily bulblets using SNP and c-PTIO. Results showed that SNP treatment promoted dormancy release, while c-PTIO inhibited it. Measurement of endogenous NO levels in the bulbs, along with enzyme activities of NOS-like and NR and gene expression levels of LoNOS-IP and LoNR, confirmed that NO plays a role in promoting dormancy release in lilies. To further elucidate the physiological mechanisms involved, we analyzed H₂O₂ levels, antioxidant enzyme activities, endogenous hormone levels, and carbohydrate metabolism in the bulbs. Findings demonstrated that NO facilitated dormancy release by increasing H₂O₂, gibberellins (GAs), indole-3-acetic acid (IAA), zeatin riboside (ZR), reducing sugars, and by accelerating the metabolism of abscisic acid (ABA) and starch. This study provides a foundation for deeper investigation into the mechanisms underlying dormancy release in lily bulbs. Full article

Sodium nitroprusside (SNP) is a powerful vasodilator approved for treating acute hypertensive crises, acute heart failure, aortic dissection, and both controlled perioperative hypotension and perioperative hypertension. Its unique ability to cause both venous and arterial dilation makes it an invaluable option in critical care settings. Despite concerns regarding its manageability due to potential toxicity, it is a safe choice if properly used, as highlighted by its short half-life and minimal side effects. This review aims to summarize its pharmacological properties, toxicology, and various clinical applications, particularly focusing on acute heart failure and hypertensive emergencies. Full article