scholarly journals Effect ofAurantii Fructus Immaturus Flavonoidon the Contraction of Isolated Gastric Smooth Muscle Strips in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Zhenyu Wu ◽  
Shengsheng Zhang ◽  
Peicai Li ◽  
Xiaofang Lu ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cyclic Guanosine Monophosphate ◽  
Inhibitory Effect ◽  
Guanosine Monophosphate ◽  
Muscle Strip ◽  
Circular Smooth Muscle ◽  
Gastric Smooth Muscle ◽  
Underlying Mechanisms ◽  
Oxide Synthase ◽  
Dose Dependent

This study was designed to investigate the effect ofAurantii fructus immaturus flavonoid(AFIF) on the contraction of isolated gastric smooth muscle in rats and explore its underlying mechanisms. Isolated antral longitudinal smooth muscle strip (ALSMS) and pyloric circular smooth muscle strip (PCSMS) of rats were suspended in tissue chambers. The responses of ALSMS and PCSMS to administration of AFIF were observed. Cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) levels of PCSMS were measured by ELISA kits. In this study, AFIF showed no significant effect on ALSMS contraction, but it dose-dependently reduced the mean contraction amplitude of PCSMS. When the concentration of AFIF reached 3000 μg/mL, 6000 μg/mL, and 10000 μg/mL, its inhibitory effect on PCSMS contraction was significant. This effect of AFIF was weakened in Ca2+-rich environment. And Nω-nitro-L-arginine methyl (L-NAME), the inhibitor of nitric oxide synthase (NOS), significantly inhibited AFIF’s action in comparison with control (P<0.05). After incubation with AFIF for 30 min, levels of cGMP and PKG in PCSMS were significantly increased compared with control (P<0.05). Our results suggest that AFIF has a dose-dependent diastolic effect on PCSMS in rats, which may be related to the regulatory pathway of NO/cGMP/PKG/Ca2+.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

scholarly journals Changes in Gastric Smooth Muscle Cell Contraction during Pregnancy: Effect of Estrogen

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Othman A. Al-Shboul ◽  
Hanan J. Al-Rshoud ◽  
Ahmed N. Al-Dwairi ◽  
Mohammad A. Alqudah ◽  
Mahmoud A. Alfaqih ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Late Pregnancy ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Gastric Smooth Muscle ◽  
Sprague Dawley Rats ◽  
Polymerase Chain ◽  
Synthase Inhibitor

It is well known that pregnancy is associated with frequent gastrointestinal (GI) disorders and symptoms. Moreover, previous reports have shown that estrogen, which changes in levels during pregnancy, participates in the regulation of GI motility and is involved in the pathogenesis of various functional disorders in the stomach. The aim of the current study was to explore the changes in the expression of estrogen receptors (ERs) and examine the effect of estrogen on nitric oxide- (NO-) cyclic guanosine monophosphate (cGMP) pathway and thus relaxation in gastric smooth muscle cells (GSMC) during pregnancy. Single GSMC from early-pregnant and late-pregnant Sprague-Dawley rats were used. Protein and mRNA expression levels of ERs were measured via specifically designed enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), respectively. NO and cGMP levels were measured via specifically designed ELISA kits. Effect of estrogen on acetylcholine- (ACh-) induced contraction of single GSMC was measured via scanning micrometry in the presence or absence of the NO synthase inhibitor,N-nitro-L-arginine (L-NNA), or guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Estrogen increased both NO and cGMP levels and their levels were greater in early compared to late pregnancy. Expression of ERs was greater in early compared to late pregnancy. ACh induced greater contraction of GSMC in late pregnancy compared to early pregnancy. Estrogen inhibited ACh-induced contraction in both periods of pregnancy. Importantly, pretreatment of GSMC with either L-NNA or ODQ abolished estrogen inhibitory action on muscle contraction. In conclusion, GSMC contractile behavior undergoes drastic changes in response to estrogen during pregnancy and this might explain some of the pregnancy-associated gastric disorders.

scholarly journals CNP-pGC-cGMP-PDE3-cAMP Signal Pathway Upregulated in Gastric Smooth Muscle of Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-Lan Cai ◽  
Mo-Han Zhang ◽  
Xu Huang ◽  
Jing-Zhi Jiang ◽  
Li-Hua Piao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Tissue ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Signal Pathway ◽  
Diabetic Rat ◽  
Rt Pcr ◽  
Smooth Muscle Tissue ◽  
Circular Smooth Muscle ◽  
Gastric Smooth Muscle

Our previous studies have shown that CNP-NPR-B/pGC-cGMP is upregulated in the diabetic rats. The present study was designed to determine whether the upregulation of CNP-NPR-B/pGC-cGMP signal pathway affects cGMP-PDE3-cAMP signal pathway in diabetic gastric smooth muscle. The gastric smooth muscle motility was observed by using isometric measurement. PDEs expressions in diabetic gastric smooth muscle tissue were observed by using immunohistochemistry, Western blotting, and RT-PCR methods. The results demonstrated that the inhibitory effect of CNP on the spontaneous contraction of gastric antral circular smooth muscle was potentiated in STZ-induced diabetic rat. CNP-induced increase of cGMP and cAMP was much higher in diabetic gastric smooth muscle tissue than in controls. The expression of PDE3 is downregulated while the levels of gene expression of PDE1, PDE2, PDE4, and PDE5 were not altered in the diabetic gastric smooth muscle tissue. The results suggest that the sensitivity of gastric smooth muscle to CNP is potentiated via activation of CNP-pGC-cGMP-PDE3-cAMP signal pathway in STZ-induced diabetic rats, which may be associated with diabetes-induced gastric motility disorder.

Halothane but Not Isoflurane Attenuates Interleukin 1β– induced Nitric Oxide Synthase in Vascular Smooth Muscle

2001 ◽  
Vol 95 (2) ◽  
pp. 492-499 ◽  
Author(s):  
Hiroshi Maeda ◽  
Hiroshi Iranami ◽  
Manabu Yamamoto ◽  
Koji Ogawa ◽  
Yoshihiro Morikawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Rat Aorta ◽  
Guanosine Monophosphate ◽  
Inos Mrna ◽  
Oxide Synthase

Background Inducible nitric oxide synthase (iNOS) is induced by endotoxin or cytokines, such as interleukin (IL)-1, through a protein synthesis pathway. Halothane reportedly inhibits protein synthesis in various tissues. The aim of the current study was to examine the effect of halothane on the IL-1beta-evoked induction of NOS in vascular smooth muscle. Methods After removal of the endothelium, arterial rings of rat aorta were mounted in an isometric force recording system. The effects of halothane (1.0-3.0%) or isoflurane (3.0%) on IL-1beta (20 ng/ml)-induced inhibition of the contractile responses to KCl (30 mM) and phenylephrine (10(-9)-10(-5) M) were studied. The cyclic guanosine monophosphate and cyclic adenosine monophosphate contents were determined by radioimmunoassay. Expression of iNOS and iNOS mRNA were measured by Western or Northern blot analysis, respectively. Results Halothane (1.0-3.0%) but not isoflurane (3%) significantly reduced the ML-1beta-induced inhibition of contraction in a concentration-dependent manner. The cyclic guanosine monophosphate content of the vascular smooth muscle increased significantly after a 5-h exposure to IL-1beta. Halothane at 3.0% significantly inhibited the increase in cyclic guanosine monophosphate content induced by IL-1beta. Halothane had no effect on cyclic adenosine monophosphate content. IL-1beta-induced expression of iNOS and iNOS mRNA in the rat aorta were inhibited significantly by halothane. Conclusion The current study demonstrated that halothane but not isoflurane inhibits IL-1beta-stimulated hyporesponsiveness to vasoconstrictive agents in vascular smooth muscle and that this inhibitory effect of halothane involves the inhibition of iNOS mRNA expression. Thus, these findings suggest that halothane may have some sites to affect nitric oxide-signaling pathway.

scholarly journals Quantitative Analysis of Factors Regulating Angiogenesis for Stem Cell Therapy

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1212
Author(s):  
Takahiro Shimazaki ◽  
Nobuhiro Noro ◽  
Kazuhiro Hagikura ◽  
Taro Matsumoto ◽  
Chikako Yoshida-Noro
Keyword(s):  
Molecular Mechanisms ◽  
Culture Supernatant ◽  
Inhibitory Effect ◽  
Cell Culture Supernatant ◽  
Promoting Effect ◽  
Disease Treatment ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Dose Dependent ◽  
Oxidative Stress Related Gene

(1) Background: The control of angiogenesis is essential in disease treatment. We investigated angiogenesis-promoting or -suppressing factors and their molecular mechanisms. (2) Methods: Angiogenesis from HUVECs was quantitatively analyzed using the Angiogenesis Analysis Kit (Kurabo, Osaka, Japan). Human rAng-1-producing 107-35 CHO cells or mouse DFAT-D1 cells were co-cultured with HUVEC. Antioxidant polyphenols were added to the culture. Gene expression was analyzed by RT-PCR. (3) Results: The addition of rAng-1-producing cells, their culture supernatant, or commercially available rAng-1 showed a promoting effect on angiogenesis. The co-culture of DFAT-D1 cells promoted angiogenesis. Polyphenols showed a dose-dependent inhibitory effect on angiogenesis. Luteolin and quercetin showed remarkable anti-angiogenic effects. The expression of vWF, Flk1, and PECAM-1 was increased by adding rAng-1-producing cell culture supernatant. Polyphenols suppressed these genes. Apigenin and luteolin markedly suppressed α-SMA and Flk1. Resveratrol and quercetin enhanced the expression of PPARγ, and luteolin suppressed the expression of COX-1. The expression of endothelial nitric oxide synthase (eNOS), an oxidative stress-related gene, was slightly increased by luteolin. These results suggest that polyphenols induce ROS reduction. (4) Conclusions: We showed the promoting effect of Ang-1 or DFAT and the suppressing effect of polyphenols on angiogenesis and studied their molecular mechanisms. These results help control angiogenesis in regenerative therapy.

Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations

1998 ◽  
Vol 7 (2) ◽  
pp. 131-140 ◽  
Author(s):  
J McHugh ◽  
DJ Cheek
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular System ◽  
Biological Activities ◽  
Vascular Diseases ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Physical Stimuli ◽  
Artery Disease

The endothelial cells of the vascular system are responsible for many biological activities that maintain vascular homeostasis. Responding to a variety of chemical and physical stimuli, the endothelium elaborates a host of vasoactive agents. One of these agents, endothelium-derived relaxing factor, now accepted as nitric oxide, influences both cellular constituents of the blood and vascular smooth muscle. A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G. Acting by this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation. Derangements in endothelial production of nitric oxide are implicated as both cause and consequence of vascular diseases, including hypertension, atherosclerosis, and coronary artery disease.

scholarly journals The Use of Vasoactive Drugs in the Treatment of Male Erectile Dysfunction: Current Concepts

2020 ◽  
Vol 9 (9) ◽  
pp. 2987
Author(s):  
George T. Kedia ◽  
Stefan Ückert ◽  
Dimitrios Tsikas ◽  
Armin J. Becker ◽  
Markus A. Kuczyk ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Erectile Dysfunction ◽  
Cyclic Gmp ◽  
Muscle Relaxation ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Smooth Muscle Relaxation ◽  
Vasoactive Drugs ◽  
Erectile Tissue ◽  
Orally Active

It is widely accepted that disorders of the male (uro)genital tract, such as erectile dysfunction (ED) and benign diseases of the prostate (lower urinary tract symptomatology or benign prostatic hyperplasia), can be approached therapeutically by influencing the function of both the vascular and non-vascular smooth muscle of the penile erectile tissue or the transition zone/periurethral region of the prostate, respectively. As a result of the discovery of nitric oxide (NO) and cyclic guanosine monophosphate (GMP) as central mediators of penile smooth muscle relaxation, the use of drugs known to increase the local production of NO and/or elevate the intracellular level of the second messenger cyclic GMP have attracted broad attention in the treatment of ED of various etiologies. Specifically, the introduction of vasoactive drugs, including orally active inhibitors of the cyclic GMP-specific phosphodiesterase (PDE) 5, has offered great advantage in the pharmacotherapy of ED and other diseases of the genitourinary tract. These drugs have been proven efficacious with a fast on-set of action and an improved profile of side-effects. This review summarizes current strategies for the treatment of ED utilizing the application of vasoactive drugs via the oral, transurethral, topical, or self-injection route.

scholarly journals Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 121
Author(s):  
Swami Prabhuling ◽  
Yasinalli Tamboli ◽  
Prafulla B. Choudhari ◽  
Manish S. Bhatia ◽  
Tapan Kumar Mohanta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Corpus Cavernosum ◽  
Active Role ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Muscle Relaxant Activity

Nitric oxide (NO) is considered to be one of the most important intracellular messengers that play an active role as neurotransmitter in regulation of various cardiovascular physiological and pathological processes. Nitric oxide (NO) is a major factor in penile erectile function. NO exerts a relaxing action on corpus cavernosum and penile arteries by activating smooth muscle soluble guanylate cyclase and increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP). Phophodiesterase (PDE) inhibitors have potential therapeutic applications. NO hybridization has been found to improve and extend the pharmacological properties of the parental compound. The present study describes the synthesis of novel furoxan coupled spiro-isoquinolino-piperidine derivatives and their smooth muscle relaxant activity. The study reveals that, particularly 10d (1.50 ± 0.6) and 10g (1.65 ± 0.7) are moderate PDE 5 inhibitors as compared to Sidenafil (1.43 ± 0.5). The observed effect was explained by molecular modelling studies on phosphodiesterase.

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