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Michaela L Sundqvist, Jon O Lundberg, Eddie Weitzberg
The nitrate-nitrite-nitric oxide pathway has emerged as a significant source of nitric oxide (NO) bioactivity. Dietary intake of inorganic nitrate has a number of cardiovascular effects as well as a decrease in oxygen cost during exercise and a reduction in resting metabolic rate (RMR). Oral bacteria have a key role in bioactivation of inorganic nitrate since they catalyse the conversion of salivary nitrate to the more reactive nitrite anion. Recent studies demonstrate that blood pressure increases with the use of an antiseptic mouthwash, indicating that endogenous, NO-synthase derived nitrate is recycled into nitrite and NO, sufficiently to modulate cardiovascular function...
October 18, 2016: Nitric Oxide: Biology and Chemistry
Caifeng Jiao, Pei Wang, Runqiang Yang, Lu Tian, Zhenxin Gu
In this study, in order to investigate the role of inositol 1,4,5-trisphosphate (IP3) in nitric oxide-guanosine 3',5'-cyclic monophosphate (NO-cGMP)-induced isoflavone accumulation in soybean sprouts under UV-B radiation, the sprouts were treated with donors and inhibitors of NO and cGMP as well as IP3 inhibitor. Results show that NO, with cGMP as a second messenger, stimulates IP3 accumulation under UV-B radiation. Consistent with the increase in IP3 content, the up-regulation of gene and protein expression of phosphoinositide-specific phospholipase C (PI-PLC) in response to sodium nitroprusside (SNP) (exogenous NO donor) and 8-Br-cGMP (cGMP analog) was also observed...
October 21, 2016: Journal of Agricultural and Food Chemistry
Caroline Honaiser Lescano, Ivan Pires de Oliveira, Tiago Zaminelli, Débora da Silva Baldivia, Luan Ramos da Silva, Mauro Napolitano, Camila Bitencourt Mendes Silvério, Nilton Lincopan, Eliana Janet Sanjinez-Argandoña
Campomanesia adamantium (Myrtaceae) is a medicinal plant distributed in Brazilian Cerrado. Different parts of this plant are used in popular medicine for treatment of several diseases like fever, diarrhea, hypercholesterolemia and rheumatism. The aim of this work was to evaluate the inhibition of heat-stable enterotoxin type A (STa) by gallic acid present in the peel of C. adamantium fruit and assays to assess the antidiarrheal activity, anti-inflammatory and cytotoxic properties of peel extract using the T84 cell line model...
2016: PloS One
Tong Zhang, Chunqiang Zhang, Xiaomei Fan, Ruilan Li, Jiaxin Zhang
C-type natriuretic peptide (CNP) has been considered as a physiological meiotic inhibitor that stimulates the cGMP production by cumulus cell natriuretic peptide receptor 2 (NPR2), which inhibits oocyte phosphodiesterase type 3 activity and increases cAMP. In this study, we explored the effect of CNP pretreatment on the in vitro maturation (IVM) of bovine oocytes by examining changes in cleavage rate, blastocyst formation, mitochondrial DNA (mtDNA) copy number, reactive oxygen species (ROS) level, glutathione (GSH) content, and redox state...
October 19, 2016: In Vitro Cellular & Developmental Biology. Animal
Francislaine Aparecida Lívero, Jacqueline Vergutz Menetrier, Emerson Luiz Botelho Lourenço, Arquimedes Gasparotto Junior
Heart failure, hypertension, cirrhosis and nephritic syndrome are among conditions that alter volume and composition of body fluids and are modulated by diuretics. Natural products are important source of diuretics and have been considered remarkable alternative with greater effectiveness and fewer side effects. However, many of these plants used in traditional medicine must be scientifically assessed about their efficacy and toxicity. Despite the large number of published articles claiming that plants or plant-derived components may act as diuretic agents, few studies have addressed the mechanism of action of medicinal plants...
October 14, 2016: Current Pharmaceutical Design
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
Riccardo Sarzani
Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are the cardiac natriuretic peptides (NP), true "cardiometabolic" hormones well known for their renal, endocrine and cardiovascular activities leading to reduced sodium reabsorption and arterial blood pressure. These effects are mainly mediated by the second messenger cGMP that also stimulates lipolysis, mitochondriogenesis and a thermogenic program with potency similar to catecholamines. Two distinct NP receptors modulate the final response to cardiac NP: the cGMP-signaling receptor NPRA and the clearance receptor NPRC...
September 2016: Journal of Hypertension
Jian-Jun Wen, Xianxiu Wan, John Thacker, Nisha Jain Garg
BACKGROUND: Chagasic cardiomyopathy (CCM) caused by Trypanosoma cruzi (Tc) infection is prevalent in Latin America and recognized as an emerging infectious heart disease in the US. The NO-cGMP-PKG1α pathway maintains cardiac homeostasis and inotropy and may be disturbed due to phosphodiesterase (PDE5) mediated cGMP catabolism in CCM. METHODS AND RESULTS: C57BL/6 mice were infected with Tc, and at the end of acute parasitemia (i.e. 45 days post-infection), treated with sildenafil (SIL, 1 mg/kg) twice per week for 3 weeks...
June 2016: JACC. Basic to Translational Science
D F Dubeibe, M C Caldas-Bussiere, V L Maciel, W V Sampaio, C R Quirino, P B D Gonçalves, M P De Cesaro, M R Faes, C S Paes de Carvalho
Nitric oxide (NO) is identified as a signaling molecule involved in many cellular or physiological functions, including meiotic maturation of cattle oocytes. This study aimed to evaluate the effect of supplementation of culture medium with the L-arginine (L-arg, NO synthesis precursor) in nuclear maturation of oocytes, concentrations of nitrate/nitrite, progesterone (P4), and 17β-estradiol (E2) in the culture medium; and the cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) intracellular concentrations in the cumulus-oocyte complexes (COCs) during the first hours of maturation in the presence of hemisections (HSs) of the follicular wall (control -ve)...
September 17, 2016: Theriogenology
Gayatri Padhy, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, Niroj Kumar Sethy
Padhy Gayatri, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, and Niroj Kumar Sethy. Plasma proteomics of Ladakhi natives reveal functional regulation between renin-angiotensin system and eNOS-cGMP pathway. High Alt Med Biol. 16:000-000, 2016.-Humans have been living in high altitudes for more than 25,000 years but the molecular pathways promoting survival and performance in these extreme environments are not well elucidated. In an attempt to understand human adaptation to high altitudes, we used two-dimensional gel electrophoresis combined with MALDI-TOF/TOF to identify plasma proteins and associated pathways of ethnic Ladakhi natives residing at 3520 m...
October 14, 2016: High Altitude Medicine & Biology
Hannes Schmidt, Stefanie Peters, Katharina Frank, Lai Wen, Robert Feil, Fritz G Rathjen
A cGMP signaling pathway, comprising C-type natriuretic peptide (CNP), its guanylate cyclase receptor Npr2, and cGMP-dependent protein kinase I (cGKI), is critical for the bifurcation of dorsal root ganglion (DRG) and cranial sensory ganglion axons when entering the mouse spinal cord and the hindbrain, respectively. However, the identity and functional relevance of phosphodiesterases (PDEs) that degrade cGMP in DRG neurons are not completely understood. Here we asked whether regulation of the intracellular cGMP concentration by PDEs modulates the branching of sensory axons...
October 14, 2016: European Journal of Neuroscience
Kristen Kokkonen, David A Kass
Cyclic nucleotide phosphodiesterases (PDEs) form an 11-member superfamily comprising 100 different isoforms that regulate the second messengers cyclic adenosine or guanosine 3',5'-monophosphate (cAMP or cGMP). These PDE isoforms differ with respect to substrate selectivity and their localized control of cAMP and cGMP within nanodomains that target specific cellular pools and synthesis pathways for the cyclic nucleotides. Seven PDE family members are physiologically relevant to regulating cardiac function, disease remodeling of the heart, or both: PDE1 and PDE2, both dual-substrate (cAMP and cGMP) esterases; PDE3, PDE4, and PDE8, which principally hydrolyze cAMP; and PDE5A and PDE9A, which target cGMP...
October 12, 2016: Annual Review of Pharmacology and Toxicology
Kaivan Khavandi, Rachael L Baylie, Sarah A Sugden, Majid Ahmed, Viktoria Csato, Philip Eaton, David C Hill-Eubanks, Adrian D Bonev, Mark T Nelson, Adam S Greenstein
Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues...
October 11, 2016: Science Signaling
Michael A Hill, Andrew P Braun
Local blood flow autoregulation in response to intraluminal pressure requires small artery myogenic vasoconstriction, the extent of which is thought to be governed by a feedback process that depends on Ca(2+) signaling. In this issue of Science Signaling, Khavandi et al suggest a role for cyclic guanosine monophosphate (cGMP)-dependent protein kinase G Iα (PKGIα) activated by oxidants in a cGMP-independent manner.
October 11, 2016: Science Signaling
Salvador Damián-Zamacona, Paola Toledo-Ibelles, Mabel Z Ibarra-Abundis, Laura Uribe-Figueroa, Enrique Hernández-Lemus, Karla Paola Macedo-Alcibia, Blanca Delgado-Coello, Jaime Mas-Oliva, Juan Pablo Reyes-Grajeda
BACKGROUND: Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved. OBJECTIVE: The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli...
2016: PloS One
S A Coavoy-Sánchez, L Rodrigues, S A Teixeira, A G Soares, R Torregrossa, M E Wood, M Whiteman, S K P Costa, M N Muscará
Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved...
October 6, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Anees A Syed, Shibani Lahiri, Divya Mohan, Guru R Valicherla, Anand P Gupta, Mohammed Riyazuddin, Sudhir Kumar, Rakesh Maurya, Kashif Hanif, Jiaur R Gayen
ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus wallichiana Planchon (Himalayan Elm), a traditional medicinal plant, used in fracture healingin folk tradition of Uttarakhand, Himalaya, India. It is also used as diuretic. U. rhynchophylla, native to China, known as Gou Teng in Chinese medicine, is used for hypertension (WHO). U. macrocarpa has antihypertensive and vasorelaxant activity. However, no detailed studies related to hypertension have been reported previously, so we have explored the antihypertensive activity of U...
October 5, 2016: Journal of Ethnopharmacology
Lourdes Dias, Mariana A P Rodrigues, Bruna R Inoue, Renata L Rodrigues, André L Rennó, Valéria B de Souza, Frank D Torres-Huaco, Norma C Sousa, Alessandra Stroka, Anibal R Melgarejo, Stephen Hyslop
In this work, we examined some mechanisms involved in the hypotension caused by Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and gradually returned to baseline over 60 min. Pretreatment of rats with the non-selective nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) did not attenuate the early phase of venom-induced hypotension, but abolished the recovery phase and resulted in rapid death; a similar effect was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ...
October 5, 2016: Toxicon: Official Journal of the International Society on Toxinology
Masashi Tawa, Tomio Okamura
Coronary artery disease is associated with oxidative stress due to the excessive generation of free radicals in the vascular wall. This study investigated the impact of tert-butyl hydroperoxide (t-BuOOH), a peroxyl radical generator, on the redox state of soluble guanylate cyclase (sGC) in isolated monkey coronary arteries. Helically cut strips of endothelium-intact monkey coronary arteries treated with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (10 μmol/L) were exposed for approximately 60 min to either no drug or t-BuOOH (100 μmol/L) in the presence and absence of α-tocopherol (300 μmol/L)...
October 2016: Pharmacology Research & Perspectives
Jennifer L Krill, Ken Dawson-Scully
While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms...
2016: PloS One
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