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https://www.readbyqxmd.com/read/29778746/betulinic-acid-a-natural-pde-inhibitor-restores-hippocampal-camp-cgmp-and-bdnf-improve-cerebral-blood-flow-and-recover-memory-deficits-in-permanent-bccao-induced-vascular-dementia-in-rats
#1
Madhu Kaundal, Saima Zameer, Abul Kalam Najmi, Suhel Parvez, Mohd Akhtar
Vascular dementia (VaD) is the second most common form of senile dementia, embraces memory deficits, neuroinflammation, executive function damage, mood and behavioral changes and abnormal cerebral blood flow. The purpose of the study was to explore the therapeutic potential of betulinic acid in bilateral common carotid artery occlusion (BCCAO) induced VaDin experimental rats.VaD was induced by BCCAO in rats and betulinic acid (10 and 15mg/kg/day po) was administered 1 week after surgery. The cerebral blood pressure of the animal was recorded before and after the treatment using Laser Doppler flow meter...
May 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29777732/antinociceptive-effect-of-tadalafil-in-various-pain-models-involvement-of-opioid-receptors-and-nitric-oxide-cyclic-gmp-pathways
#2
Mohammad M Mehanna, Souraya Domiati, Hania Nakkash Chmaisse, Ahmed El Mallah
Nitric oxide has been proven to play an important role in nociception, accordingly, its promoters, phosphodiesterase inhibitors have been investigated as pain response modulators. Aiming to evaluate the central effect of tadalafil, a phosphodiesterase 5 inhibitor, and to determine its EC50, tail flick and hot plate tests were utilized. On the other hand, its nociceptive peripheral analgesic effect was assessed through acetic-acid induced writhing model. Formalin test was used to appraise both non-inflammatory and inflammatory pain responses...
May 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29775416/downregulation-of-the-%C3%AE-1-and-%C3%AE-1-subunit-of-sgc-in-arterial-smooth-muscle-cells-of-opscc-is-hpv-independent
#3
Y Korkmaz, H C Roggendorf, O G Siefer, J Seehawer, T Imhof, M Plomann, W Bloch, A Friebe, C U Huebbers
The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an α and β subunit. NO binds to heme of the β1 -subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required...
May 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29773995/hypoxia-reoxygenation-of-rat-renal-arteries-impairs-vasorelaxation-via-modulation-of-endothelium-independent-sgc-cgmp-pkg-signaling
#4
Diana Braun, Christa Zollbrecht, Stefanie Dietze, Rudolf Schubert, Stefan Golz, Holger Summer, Pontus B Persson, Mattias Carlström, Marion Ludwig, Andreas Patzak
Ischemia/reperfusion injury holds a key position in many pathological conditions such as acute kidney injury and in the transition to chronic stages of renal damage. We hypothesized that besides a reported disproportional activation of vasoconstrictor response, hypoxia/reoxygenation (H/R) adversely affects endothelial dilatory systems and impairs relaxation in renal arteries. Rat renal interlobar arteries were studied under isometric conditions. Hypoxia was induced by application of 95% N2 , 5% CO2 for 60 min to the bath solution, followed by a 10 min period of reoxygenation (95% O2 , 5% CO2 )...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29773582/activation-of-large-conductance-calcium-activated-k-channels-by-nitric-oxide-mediates-apelin-induced-relaxation-of-coronary-arteries
#5
Amreen Mughal, Chengwen Sun, Stephen T O'Rourke
Apelin increases coronary blood flow, cardiac contractility and cardiac output. Based on these favorable hemodynamic effects, apelin and apelin-like analogs are being developed for treating heart failure and related disorders; however, the molecular mechanisms underlying apelin-induced coronary vasodilation are unknown. This study aimed to elucidate the signaling pathways by which apelin causes smooth muscle relaxation in coronary arteries. Receptors for apelin (APJ receptors) were expressed in coronary arteries, as determined by Western blot and PCR analyses...
May 17, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29766323/cgmp-at-the-centre-of-attention-emerging-strategies-for-activating-the-cardioprotective-pkg-pathway
#6
REVIEW
Min Park, Peter Sandner, Thomas Krieg
The nitric oxide (NO)-protein kinase G (PKG) pathway has been known for some time to be an important target for cardioprotection against ischaemia/reperfusion injury and heart failure. While many approaches for reducing infarct size in patients have failed in the past, the advent of novel drugs that modulate cGMP and its downstream targets shows very promising results in recent preclinical and clinical studies. Here, we review main aspects of the NO-PKG pathway in light of recent drug development and summarise potential cardioprotective strategies in which cGMP is the main player...
May 15, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29760016/diabetes-induced-cardiomyocyte-passive-stiffening-is-caused-by-impaired-insulin-dependent-titin-modification-and-can-be-modulated-by-neuregulin-1
#7
Anna-Eliane Hopf, Christian Andresen, Sebastian Kötter, Malgorzata Isic, Kamila Ulrich, Senem Sahin, Sabine Bongardt, Wilhelm Roell, Felicitas Drove, Nina Scheerer, Leni Vandekerckhove, Gilles W De Keulenaer, Nazha Hamdani, Wolfgang A Linke, Martina Krüger
<u>Rationale:</u> Increased titin-dependent cardiomyocyte tension is a hallmark of heart failure with preserved ejection fraction (HFpEF) associated with type-2 diabetes mellitus (T2DM). However, the insulin-related signaling pathways that modify titin-based cardiomyocyte tension, thereby contributing to modulation of diastolic function, are largely unknown. <u>Objective:</u> We aimed to determine how impaired insulin signaling affects titin expression and phosphorylation and thus increases passive cardiomyocyte tension, and whether metformin or neuregulin-1 can correct disturbed titin modifications and increased titin-based stiffness...
May 14, 2018: Circulation Research
https://www.readbyqxmd.com/read/29756024/preparation-and-preclinical-evaluation-of-a-68-ga-labelled-c-rgdfk-conjugate-comprising-the-bifunctional-chelator-nodia-me
#8
Tilman Läppchen, Jason P Holland, Yvonne Kiefer, Mark D Bartholomä
Background: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of 68 Ga- and 64 Cu-based radiopharmaceuticals. Here, a 68 Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the αv ß3 -targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of 68 Ga-labelled radiotracers...
2018: EJNMMI Radiopharmacy and Chemistry
https://www.readbyqxmd.com/read/29755973/identification-of-loop-d-domain-amino-acids-in-the-human-aquaporin-1-channel-involved-in-activation-of-the-ionic-conductance-and-inhibition-by-aqb011
#9
Mohamad Kourghi, Michael L De Ieso, Saeed Nourmohammadi, Jinxin V Pei, Andrea J Yool
Aquaporins are integral proteins that facilitate the transmembrane transport of water and small solutes. In addition to enabling water flux, mammalian Aquaporin-1 (AQP1) channels activated by cyclic GMP can carry non-selective monovalent cation currents, selectively blocked by arylsulfonamide compounds AqB007 (IC50 170 μM) and AqB011 (IC50 14 μM). In silico models suggested that ligand docking might involve the cytoplasmic loop D (between AQP1 transmembrane domains 4 and 5), but the predicted site of interaction remained to be tested...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29753142/heme-oxygenase-1-inhibits-spring-viremia-of-carp-virus-replication-through-carbon-monoxide-mediated-cyclic-gmp-protein-kinase-g-signaling-pathway
#10
Cong Li, Lijuan Li, Ling Jin, Junfa Yuan
Spring viremia of carp virus (SVCV) is the etiological agent of spring viremia of carp (SVC) and causes mass mortality in common carp (Cyprinus carpio). Currently, no effective treatments or commercial vaccines against SVCV are available. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme to produce carbon monoxide (CO), biliverdin and ferrous iron (Fe2+), exerts anti-oxidant, antiinflammatory and anti-apoptotic properties. Previous studies demonstrated that nuclear factor-erythroid 2 related factor 2 (Nrf2) functions as an important upstream regulator of HO-1 and exhibits robust activity against SVCV infection...
May 9, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29752430/pigment-epithelium-derived-factor-hinders-photoreceptor-cell-death-by-reducing-intracellular-calcium-in-the-degenerating-retina
#11
Antonella Comitato, Preeti Subramanian, Giandomenico Turchiano, Monica Montanari, S Patricia Becerra, Valeria Marigo
Calcium ions play a critical role in neuronal cell death. Pigment epithelium-derived factor (PEDF) is a promising neuroprotective protein for photoreceptor cells but the mechanisms mediating its effects against retinal degeneration are still not well characterized. We addressed this question in the rd1 degenerating mouse retina that bears a mutation in the Pde6b gene encoding one subunit of the phosphodiesterase enzyme. Loss of phosphodiesterase activity in rod photoreceptor cells increases cyclic guanosine monophosphate (cGMP) levels leading to a rise in intracellular calcium...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29752414/ligand-binding-and-activation-properties-of-the-purified-bacterial-cyclic-nucleotide-gated-channel-sthk
#12
Philipp A M Schmidpeter, Xiaolong Gao, Vikrant Uphadyay, Jan Rheinberger, Crina M Nimigean
Cyclic nucleotide-modulated ion channels play several essential physiological roles. They are involved in signal transduction in photoreceptors and olfactory sensory neurons as well as pacemaking activity in the heart and brain. Investigations of the molecular mechanism of their actions, including structural and electrophysiological characterization, are restricted by the availability of stable, purified protein obtained from accessible systems. Here, we establish that SthK, a cyclic nucleotide-gated (CNG) channel from Spirochaeta thermophila , is an excellent model for investigating the gating of eukaryotic CNG channels at the molecular level...
May 11, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29747754/mechanism-of-resveratrol-induced-relaxation-of-the-guinea-pig-fundus
#13
Ching-Chung Tsai, Shu-Leei Tey, Ming-Che Lee, Ching-Wen Liu, Yu-Tsun Su, Shih-Che Huang
BACKGROUND: Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. PURPOSE: Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29747747/tiger-nut-and-walnut-extracts-modulate-extracellular-metabolism-of-atp-and-adenosine-through-the-nos-cgmp-pkg-signalling-pathway-in-kidney-slices
#14
Ayodeji A Olabiyi, Fabiano B Carvalho, Nathieli B Bottari, Vera M Morsch, Ademir F Morel, Ganiyu Oboh, Maria Rosa Schetinger
BACKGROUND: Tiger nut (Cyperus esculentus L.) and walnut (Tetracarpidium conophorum Müll. Arg.) have been reportedly used in the treatment of inflammatory diseases such as atherosclerosis, prevent heart attack and improve blood circulation, reduce serum cholesterol level as well as inhibit oxidation reactions. PURPOSE: This study investigated the effect of tiger nut and walnut hydro-alcoholic extracts on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in kidney slices...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29742029/nitric-oxide-augments-single-persistent-na-channel-currents-via-the-cgmp-pkg-signaling-pathway-in-kenyon-cells-isolated-from-the-cricket-mushroom-bodies
#15
Mariko Ikeda, Masami Yoshino
The nitric oxide (NO)/cyclic GMP signaling pathway has been suggested to be important in the formation of olfactory memory in insects. However, the molecular targets of the NO signaling cascade in the central neurons associated with olfactory learning and memory have not been fully analyzed. In this study, we investigated the effects of NO donors on single voltage-dependent Na+ channels in intrinsic neurons, called Kenyon cells, in the mushroom bodies in the brain of the cricket. Step depolarization on cell-attached patch membranes induces single-channel currents with fast-activating and -inactivating brief openings at the beginning of the voltage steps followed by more persistently recurring brief openings all along the 150-ms pulses...
May 9, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29738821/discovery-and-development-of-sgc-stimulators-for-the-treatment-of-pulmonary-hypertension-and-rare-diseases
#16
REVIEW
Peter Sandner, Eva-Maria Becker-Pelster, Johannes Peter Stasch
The NO/sGC/cGMP signaling cascade plays a pivotal role in regulation of cardiovascular, cardiopulmonary and cardiorenal diseases and impairment of this cascade results in severe pathologies. Therefore, pharmacological interventions, targeting this pathway are promising strategies for treating a variety of diseases. Nitrates, supplementing NO and, PDE5 inhibitors preventing cGMP degradation, are used for angina pectoris treatment and the treatment of pulmonary arterial hypertension (PAH), respectively. More recently, a new class of drugs which directly stimulate the sGC enzyme and trigger NO-independent cGMP production was introduced and termed sGC stimulators...
May 5, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29736011/s-nitrosylation-of-nos-pathway-mediators-in-the-penis-contributes-to-cavernous-nerve-injury-induced-erectile-dysfunction
#17
Biljana Musicki, Anil K Bhunia, Serkan Karakus, Arthur L Burnett
cGMP-independent nitric oxide (NO) signaling occurs via S-nitrosylation. We evaluated whether aberrant S-nitrosylation operates in the penis under conditions of cavernous nerve injury and targets proteins involved in regulating erectile function. Adult male Sprague-Dawley rats underwent bilateral cavernous nerve crush injury (BCNI) or sham surgery. Rats were given a denitrosylation agent N-acetylcysteine (NAC, 300 mg/kg/day) or vehicle in drinking water starting 2 days before BCNI and continuing for 2 weeks following surgery...
May 8, 2018: International Journal of Impotence Research
https://www.readbyqxmd.com/read/29734386/renal-papillary-tip-extract-stimulates-bnp-production-and-excretion-from-cardiomyocytes
#18
Itaru Goto, Ryuji Okamoto, Ryotaro Hashizume, Noboru Suzuki, Rie Ito, Keiichi Yamanaka, Hiromitsu Saito, Hiroshi Kiyonari, Isao Tawara, Yuki Kageyama, Yoshito Ogihara, Yusuf Ali, Norikazu Yamada, Naoyuki Katayama, Masaaki Ito
BACKGROUND: Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear. METHODS AND RESULTS: We developed a BNP reporter mouse and occasionally found that this promoter was activated specifically in the papillary tip of the kidneys, and its activation was not accompanied by BNP mRNA expression...
2018: PloS One
https://www.readbyqxmd.com/read/29732286/safety-and-efficacy-of-daily-revactin-%C3%A2-in-men-with-erectile-dysfunction-a-3-month-pilot-study
#19
Sabine Nguyen, Jacob Rajfer, Magda Shaheen
Background: The earliest sign of an ongoing change in a man's erectile function (EF) is the increase in his refractory period. This is due to the onset of an aging related apoptosis of the corporal smooth muscle cells (CSMC) as a result of oxidative stress (ROS) within the CSMC itself. In response, the CSMC begin to upregulate the inducible nitric oxide synthase (iNOS) enzyme presumably to achieve high levels of nitric oxide (NO) used to combat ROS. Treatment of aged rats for 2 months with the nutraceutical Revactin® , known to stimulate the iNOS-NO-cGMP pathway in CSMC, resulted in (I) an increase in CSMC content with a decrease in corporal fibrosis, (II) decrease in systemic ROS, and (III) improvement in EF...
April 2018: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29727215/acute-stimulation-of-the-soluble-guanylate-cyclase-does-not-impact-on-left-ventricular-capacitance-in-normal-and-hypertrophied-porcine-hearts-in-vivo
#20
Alessio Alogna, Michael Schwarzl, Martin Manninger, Nazha Hamdani, Birgit Zirngast, Benjamin Kloth, Paul Steendijk, Jochen Verderber, David Zweiker, Dirk Westermann, Stefan Blankenberg, Heinrich Maechler, Carsten Tschöpe, Wolfgang A Linke, Gunther Marsche, Burkert M Pieske, Heiner Post
Experimental data indicate that stimulation of the nitric oxide (NO) - soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy, landrace pigs and seven pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume-relationships (EDPVR) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 μg/kg/min for 30 min, respectively)...
May 4, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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