scholarly journals Icariin Inhibits Pulmonary Hypertension Induced by Monocrotaline through Enhancement of NO/cGMP Signaling Pathway in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Li-sheng Li ◽  
Yun-mei Luo ◽  
Juan Liu ◽  
Yu Zhang ◽  
Xiao-xia Fu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Signaling Pathway ◽  
Guanosine Monophosphate ◽  
Tissue Homogenate ◽  
Intragastric Administration ◽  
Enos Gene ◽  
Protective Effects ◽  
Cgmp Pathway ◽  
Cgmp Signaling

It has been reported that icariin (ICA) increased contents of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by improving expression of endothelial nitric oxide synthase (eNOS) and inhibition of phosphodiesterase type 5 (PDE5). In addition, dysfunction of the NO/cGMP pathway may play a crucial role in the pathogenesis of pulmonary hypertension (PH). In this study, the potential protective effects of ICA on PH induced by monocrotaline (MCT, 50 mg/kg) singly subcutaneous injection were investigated and the possible mechanisms involved in NO/cGMP pathway were explored in male Sprague Dawley rats. The results showed that ICA (20, 40, and 80 mg/kg/d) treatment by intragastric administration could significantly ameliorate PH and upregulate the expression of eNOS gene and downregulate the expression of PDE5 gene in MCT-treated rats. Both ICA (40 mg/kg/d) and L-arginine (200 mg/kg/d), a precursor of NO as positive control, notably increased the contents of NO and cGMP in lung tissue homogenate, which were inversed by treatment withGN-nitro-L-arginine-methyl ester (L-NAME), a NOS inhibitor, and L-NAME-treatment could also inhibit the protective effects of ICA (40 mg/kg/d) on mean pulmonary artery pressure and artery remodeling and tends to inhibit right ventricle hypertrophy index. In summary, ICA is effective in protecting against MCT-induced PH in rats through enhancement of NO/cGMP signaling pathway in rats.

scholarly journals Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway

2021 ◽  
Vol 22 (8) ◽  
pp. 4225
Author(s):  
Zaidatul Akmal Othman ◽  
Zaida Zakaria ◽  
Joseph Bagi Suleiman ◽  
Victor Udo Nna ◽  
Aminah Che Romli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Profile ◽  
Signaling Pathway ◽  
Structural Damage ◽  
Vascular Inflammation ◽  
Vascular Damage ◽  
Guanosine Monophosphate ◽  
Bee Bread ◽  
Obese Rats ◽  
Cgmp Signaling

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.

Modulation of Voltage-Gated Ca2+ Current in Vestibular Hair Cells by Nitric Oxide

2007 ◽  
Vol 97 (2) ◽  
pp. 1188-1195 ◽  
Author(s):  
Angélica Almanza ◽  
Francisco Navarrete ◽  
Rosario Vega ◽  
Enrique Soto
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Hair Cells ◽  
Specific Inhibitor ◽  
Guanosine Monophosphate ◽  
Soluble Form ◽  
Patch Clamp Technique ◽  
Independent Manner ◽  
Vestibular Hair Cells ◽  
Cgmp Signaling

The structural elements of the nitric oxide–cyclic guanosine monophosphate (NO–cGMP) signaling pathway have been described in the vestibular peripheral system. However, the functions of NO in the vestibular endorgans are still not clear. We evaluated the action of NO on the Ca2+ currents in hair cells isolated from the semicircular canal crista ampullaris of the rat (P14–P18) by using the whole cell and perforated-cell patch-clamp technique. The NO donors 3-morpholinosydnonimine (SIN-1), sodium nitroprusside (SNP), and (±)-(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl-nicotinamide (NOR-4) inhibited the Ca2+ current in hair cells in a voltage-independent manner. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) prevented the inhibitory effect of SNP on the Ca2+ current. The selective inhibitor of the soluble form of the enzyme guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), also decreased the SNP-induced inhibition of the Ca2+ current. The membrane-permeant cGMP analogue 8-Br-cGMP mimicked the SNP effect. KT-5823, a specific inhibitor of cGMP-dependent protein kinase (PGK), prevented the inhibition of the Ca2+ current by SNP and 8-Br-cGMP. In the presence of N-ethylmaleimide (NEM), a sulfhydryl alkylating agent that prevents the S-nitrosylation reaction, the SNP effect on the Ca2+ current was significantly diminished. These results demonstrated that NO inhibits in a voltage-independent manner the voltage-activated Ca2+ current in rat vestibular hair cells by the activation of a cGMP-signaling pathway and through a direct action on the channel protein by a S-nitrosylation reaction. The inhibition of the Ca2+ current by NO may contribute to the regulation of the intracellular Ca2+ concentration and hair-cell synaptic transmission.

Functional localization of the nitric oxide/cGMP pathway in the salamander retina

2009 ◽  
Vol 26 (3) ◽  
pp. 275-286 ◽  
Author(s):  
JAN J. BLOM ◽  
TODD A. BLUTE ◽  
WILLIAM D. ELDRED
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Visual Information ◽  
Amacrine Cells ◽  
Cell Types ◽  
Guanosine Monophosphate ◽  
Specific Cell ◽  
No Production ◽  
Outer Retina ◽  
Cgmp Pathway

AbstractNitric oxide (NO) is a gaseous neuromodulator that has physiological functions in every cell type in the retina. Evidence indicates that NO often plays a role in the processing of visual information in the retina through the second messenger cyclic guanosine monophosphate (cGMP). Despite numerous structural and functional studies of this signaling pathway in the retina, none have examined many of the elements of this pathway within a single study in a single species. In this study, the NO/cGMP pathway was localized to specific regions and cell types within the inner and outer retina. We have immunocytochemically localized nitric oxide synthase, the enzyme that produces NO, in photoreceptor ellipsoids, four distinct classes of amacrine cells, Müller and bipolar cells, somata in the ganglion cell layer, as well as in processes within both plexiform layers. Additionally, we localized NO production in specific cell types using the NO-sensitive dye diaminofluorescein. cGMP immunocytochemistry was used to functionally localize soluble guanylate cyclase that was activated by an NO donor in select amacrine and bipolar cell classes. Analysis of cGMP and its downstream target, cGMP-dependent protein kinase II (PKGII), showed colocalization within processes in the outer retina as well as in somata in the inner retina. The results of this study showed that the NO/cGMP signaling pathway was functional and its components were widely distributed throughout specific cell types in the outer and inner salamander retina.

scholarly journals Gycine and GABA interact to regulate the nitric oxide/cGMP signaling pathway in the turtle retina

2005 ◽  
Vol 22 (6) ◽  
pp. 825-838 ◽  
Author(s):  
DOU YU ◽  
WILLIAM D. ELDRED
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Signaling Pathway ◽  
Amacrine Cells ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Double Labeling ◽  
Selective Antagonist ◽  
Cgmp Production ◽  
Cgmp Signaling

Nitric oxide (NO) is a free radical that is important in retinal signal transduction and cyclic guanosine monophosphate (cGMP) is a critical downstream messenger of NO. The NO/cGMP signaling pathway has been shown to modulate neurotransmitter release and gap junction coupling in horizontal cells and amacrine cells, and increase the gain of the light response in photoreceptors. However, many of the mechanisms controlling the production of NO and cGMP remain unclear. Previous studies have shown activation of NO/cGMP production in response to stimulation with N-methyl-d-aspartate (NMDA) or nicotine, and the differential modulation of cGMP production by GABAA and GABAC receptors (GABAARs and GABACRs). This study used cGMP immunocytochemistry and NO imaging to investigate how the inhibitory GABAergic and glycinergic systems modulate the production of NO and cGMP. Our data show that blocking glycine receptors (GLYR) with strychnine (STRY) produced moderate increases in cGMP-like immunoreactivity (cGMP-LI) in select types of amacrine and bipolar cells, and strong increases in NO-induced fluorescence (NO-IF). TPMPA, a selective GABACR antagonist, greatly reduced the increases in cGMP-LI stimulated by STRY, but did not influence the increase in NO-IF stimulated by STRY. Bicuculline (BIC), a GABAAR antagonist, however, enhanced the increases in both the cGMP-LI and NO-IF stimulated by STRY. CNQX, a selective antagonist for α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid hydrobromide/kainic acid (AMPA/KA) receptors, eliminated both the increases in cGMP-LI and NO-IF stimulated by STRY, while MK801, a selective antagonist for NMDA receptors, slightly increased the cGMP-LI and slightly decreased the NO-IF stimulated by STRY. Finally, double labeling of NO-stimulated cGMP and either GLY or GABA indicated that cGMP predominantly colocalized with GLY. Taken together, these findings support the hypothesis that GLY and GABA interact in the regulation of the NO/cGMP signaling pathway, where GLY primarily inhibits NO production and GABA has a greater effect on cGMP production. Such interacting inhibitory pathways could shape the course of signal transduction of the NO/cGMP pathway under different physiological situations.

The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine

2011 ◽  
Vol 89 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Ercan Ozdemir ◽  
Ihsan Bagcivan ◽  
Nedim Durmus ◽  
Ahmet Altun ◽  
Sinan Gursoy
Keyword(s):  
Nitric Oxide ◽  
Analgesic Effect ◽  
Soluble Guanylate Cyclase ◽  
Morphine Tolerance ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Albino Rats ◽  
Tail Flick ◽  
Analgesic Effects ◽  
Cgmp Signaling

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

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