Concept: Nitric oxide
- Journal of the International Society of Sports Nutrition
- Published almost 3 years ago
Dark chocolate (DC) is abundant in flavanols which have been reported to increase the bioavailability and bioactivity of nitric oxide (NO). Increasing NO bioavailability has often demonstrated reduced oxygen cost and performance enhancement during submaximal exercise.
Inflammation and oxidative stress play a crucial role in angiotensin (Ang) II-mediated vascular injury. Angiotensin-converting enzyme 2 (ACE2) has recently been identified as a specific Ang II-degrading enzyme but its role in vascular biology remains elusive. We hypothesized that loss of ACE2 would facilitate Ang II-mediated vascular inflammation and peroxynitrite production. 10-week wildtype (WT, Ace2(+/y)) and ACE2 knockout (ACE2KO, Ace2(-/y)) mice received with mini-osmotic pumps with Ang II (1.5 mg.kg⁻¹.d⁻¹) or saline for 2 weeks. Aortic ACE2 protein was obviously reduced in WT mice in response to Ang II related to increases in profilin-1 protein and plasma levels of Ang II and Ang-(1-7). Loss of ACE2 resulted in greater increases in Ang II-induced mRNA expressions of inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, and IL-6 without affecting tumor necrosis factor-α in aortas of ACE2KO mice. Furthermore, ACE2 deficiency led to greater increases in Ang II-mediated profilin-1 expression, NADPH oxidase activity, and superoxide and peroxynitrite production in the aortas of ACE2KO mice associated with enhanced phosphorylated levels of Akt, p70S6 kinase, extracellular signal-regulated kinases (ERK1/2) and endothelial nitric oxide synthase (eNOS). Interestingly, daily treatment with AT1 receptor blocker irbesartan (50 mg/kg) significantly prevented Ang II-mediated aortic profilin-1 expression, inflammation, and peroxynitrite production in WT mice with enhanced ACE2 levels and the suppression of the Akt-ERK-eNOS signaling pathways. Our findings reveal that ACE2 deficiency worsens Ang II-mediated aortic inflammation and peroxynitrite production associated with the augmentation of profilin-1 expression and the activation of the Akt-ERK-eNOS signaling, suggesting potential therapeutic approaches by enhancing ACE2 action for patients with vascular diseases.
The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signal-transduction pathway is impaired in many cardiovascular diseases, including pulmonary arterial hypertension (PAH). Riociguat (BAY 63-2521) is a stimulator of sGC that works both in synergy with and independently of NO to increase levels of cGMP. The aims of this study were to investigate the role of NO-sGC-cGMP signaling in a model of severe PAH and to evaluate the effects of sGC stimulation by riociguat and PDE5 inhibition by sildenafil on pulmonary hemodynamics and vascular remodeling in severe experimental PAH.
Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) play key roles in physiological and pathological responses in cardiac myocytes. The mechanisms whereby H(2)O(2)-modulated phosphorylation pathways regulate the endothelial isoform of nitric oxide synthase (eNOS) in these cells are incompletely understood. We show here that H(2)O(2) treatment of adult mouse cardiac myocytes leads to increases in intracellular Ca(2+) ([Ca(2+)](i)), and document that activity of the L-type Ca(2+) channel is necessary for the H(2)O(2)-promoted increase in sarcomere shortening and of [Ca(2+)](i). Using the chemical NO sensor Cu(2)(FL2E), we discovered that the H(2)O(2)-promoted increase in cardiac myocyte NO synthesis requires activation of the L-type Ca(2+) channel, as well as phosphorylation of the AMP-activated protein kinase (AMPK), and mitogen-activated protein kinase kinase ½ (MEK1/2). Moreover, H(2)O(2)-stimulated phosphorylations of eNOS, AMPK, MEK1/2, and ERK1/2 all depend on both an increase in [Ca(2+)](i) as well as the activation of protein kinase C (PKC). We also found that H(2)O(2)-promoted cardiac myocyte eNOS translocation from peripheral membranes to internal sites is abrogated by the L-type Ca(2+) channel blocker nifedipine. We have previously shown that kinase Akt is also involved in H(2)O(2)-promoted eNOS phosphorylation. Here we present evidence documenting that H(2)O(2)-promoted Akt phosphorylation is dependent on activation of the L-type Ca(2+) channel, but is independent of PKC. These studies establish key roles for Ca(2+)- and PKC-dependent signaling pathways in the modulation of cardiac myocyte eNOS activation by H(2)O(2).
Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either “direct” or “indirect,” referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 2 years ago
Rapid development of agriculture and fossil fuel combustion greatly increased US reactive nitrogen emissions to the atmosphere in the second half of the 20th century, resulting in excess nitrogen deposition to natural ecosystems. Recent efforts to lower nitrogen oxides emissions have substantially decreased nitrate wet deposition. Levels of wet ammonium deposition, by contrast, have increased in many regions. Together these changes have altered the balance between oxidized and reduced nitrogen deposition. Across most of the United States, wet deposition has transitioned from being nitrate-dominated in the 1980s to ammonium-dominated in recent years. Ammonia has historically not been routinely measured because there are no specific regulatory requirements for its measurement. Recent expansion in ammonia observations, however, along with ongoing measurements of nitric acid and fine particle ammonium and nitrate, permit new insight into the balance of oxidized and reduced nitrogen in the total (wet + dry) US nitrogen deposition budget. Observations from 37 sites reveal that reduced nitrogen contributes, on average, ∼65% of the total inorganic nitrogen deposition budget. Dry deposition of ammonia plays an especially key role in nitrogen deposition, contributing from 19% to 65% in different regions. Future progress toward reducing US nitrogen deposition will be increasingly difficult without a reduction in ammonia emissions.
Oxidative stress is one of the most critical factors implicated in disease conditions. Buchanania lanzan Spr. (Anacardiaceae) bark powder preparation has been reported for treating an inflammatory condition in the Ayurvedic Pharmacopoeia of India.
Nitric oxide (NO) is a gaseous molecule having key roles in many physiological processes such as germination, growth, development and senescence. It has been also shown the important role of NO as a signaling molecule in the response to a wide variety of stress situations, including both biotic and abiotic stress conditions. In the last few years, a growing number of studies have focused on NO-cell targets by several approaches such as transcriptomic and proteomic analyses. This review is centered on offering an update about the principal medium- and large-scale transcriptomic analyses performed with several NO donors including microarray, cDNA-amplification fragment length polymorphism (AFLP) and high throughput sequencing (RNA-seq technology) approaches mainly focused on the role of this reactive nitrogen species in relation to plant disease resistance. Different putative NO-responsive genes have been identified in different plant tissues and plant species by application of several NO donors suggesting the implication of NO-responsive genes with plant adaptive responses to biotic stress processes. Finally, it is also provided an overview about common transcription factor-binding sites of NO-responsive genes and the need to further analyze the different NO-targets by other omics studies.
Considering the indigenous utilization of Quercus incana Roxb., the present study deals with the investigation of antioxidant, free radical scavenging activity, total phenolic content, and antimicrobial activity of Q. incana Roxb. In vitro antioxidant activity of the plant fractions were determined by 1,1-diphenyl-2-picrylhydrazyl and nitric oxide scavenging method. Total phenolic contents were determined by gallic acid equivalent and antimicrobial activities were determined by agar well diffusion method. It was observed that Q. incana Roxb. showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. n-Butanol fraction showed maximum activity against Micrococcus leuteus with 19 mm zone of inhibition. n-Butanol fraction of Q. incana Roxb. showed immense antifungal activity against Aspergillus niger (32 mm ± 0.55) and A. flavus (28 mm ± 0.45). Similarly n-butanol fraction showed relatively good antioxidant activity with IC50 value of 55.4 ± 0.21 μg/mL. The NO scavenging activity of ethyl acetate fraction (IC50 = 23.21 ± 0.31 μg/mL) was fairly good compared to other fractions. The current study of Q. incana Roxb. suggests the presences of synergetic action of some biological active compounds that may be present in the leaves of medicinal plant. Further studies are needed to better characterize the important active constituents responsible for the antimicrobial, antioxidant and free radical scavenging activity.