The role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV and Rho-kinase in H 2 S-induced relaxation in the mouse corpus cavernosum

Aydinoglu, Fatma; Ogulener, Nuran

doi:10.1016/j.pharep.2017.02.018

Cited by 9 publications

(7 citation statements)

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“…An imbalance in AA metabolism can lead to the formation of vascular disorders. It is known that AA metabolites have an important role in different vascular beds (Spector, ; Aydinoglu & Ogulener, ). The effects of AA on the genitourinary system, in which CYP metabolites are involved, have drawn attention, but they have not been completely understood.…”

Section: Discussionmentioning

confidence: 99%

Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

et al. 2019

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We aimed to investigate the effects of epoxygenases on electrical field stimulation (EFS)-mediated nitric oxide (NO)-dependent and NO-independent nonadrenergic noncholinergic (NANC) relaxations in isolated rabbit corpus cavernosum. The tissues of 20 male adult albino rabbits (2.5-3 kg) were suspended in organ baths containing aerated Krebs solution, and isometric contractions were recorded. EFS-mediated NANC relaxations were obtained on phenylephrin (3 × 10 −5 M)-contracted tissues in the presence of guanethidine (10 −6 M) and atropine (10 −6 M). Miconazole (10 −9 -10 −4 M), 17-octadecynoic acid (ODYA) (10 −10 -10 −5 M), 14,15-epoxyeicosatrienoic acid (EET) (10 −11 -10 −8 M), 11,12-EET (10 −12 -3 × 10 −8 M) and 20-hydroxyeicosatetraenoic acid (HETE) (10 −11 -3 × 10 −8 M) were added cumulatively (n = 5-7 for each set of experiments). For NO-independent relaxations, N ω -nitro-l-arginine methyl ester (l-NAME) (10 −4 M) was added before a group of experiments. Depending on the concentration, miconazole, 17-ODYA, 14,15-EET, 11,12-EET, and 20-HETE significantly enhanced both NO-dependent and NO-independent EFS-mediated relaxations (p < 0.05). Epoxygenases showed similar effect on NO-dependent and NO-independent relaxant responses except 20-HETE which caused significantly more enhanced relaxation on NO-dependent responses (p < 0.05). No drug caused a significant relaxation response on tissues contracted with phenylephrine. Epoxygenases contribute to EFS-mediated NO-dependent and NO-independent NANC relaxations by presynaptic mechanisms, offering a new treatment alternative for erectile dysfunction which needs to be explored in further in vivo, molecular and clinical studies. K E Y W O R D S corpus cavernosum, electrical field stimulation, epoxygenase, isolated organ bath, nonadrenergic noncholinergic system 1 | INTRODUC TI ON Penile erection is a neurovascular event controlled by physiological factors and hormones (Martínez-Salamanca et al., 2010). Arousal of the pelvic plexus and the cavernosal nerves causes erection, and sympathetic nerves enable the penis to return to the flaccid state (Andersson, 2011). Erectile dysfunction (ED) is defined as the inability to achieve and continue to maintain penile erection. Nitric oxide (NO)-cyclic GMP

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Section: Discussionmentioning

confidence: 99%

Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

et al. 2019

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Section: Introductionmentioning

confidence: 99%

“…There is some experimental evidence in animal models to support a causal link between alcohol and ED (Aydinoglu et al, 2008; Leite et al, 2017; Lizarte et al, 2009; Tiraboschi et al, 2021; Yazir et al, 2012). Corpora cavernosa (CC) isolated from mice, rats or rabbits chronically exposed to alcohol show an impaired relaxation to acetylcholine or other muscarinic receptor agonists which stimulate the endothelium to release nitric oxide (NO) (Aydinoglu et al, 2008; Lizarte et al, 2009; Yazir et al, 2012). The relaxant response of CC to electrical field stimulation (EFS), which induces the release of NO from nitrergic nerves, that is, an in vitro correlate of penile erection, also has been observed to be impaired in some models of chronic exposure to alcohol (Yazir et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…The relaxant response of CC to electrical field stimulation (EFS), which induces the release of NO from nitrergic nerves, that is, an in vitro correlate of penile erection, also has been observed to be impaired in some models of chronic exposure to alcohol (Yazir et al, 2012). The effect develops after 1 week (Aydinoglu et al, 2008) to 4 weeks (Yazir et al, 2012) of treatment and is dose‐dependent (Yazir et al, 2012). These models have used chronic continuous alcohol in drinking water (Lizarte et al, 2009; Tiraboschi et al, 2021; Yazir et al, 2012) or alcohol inhalation (Aydinoglu et al, 2008), but they do not induce alcohol‐dependence.…”

Section: Introductionmentioning

confidence: 99%

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Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice

Olivencia

Biedma-Elduayen

Giménez-Gómez

et al. 2023

British J Pharmacology

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Background and purposeAlcohol abuse has been associated with erectile dysfunction (ED), but the implicated molecular mechanisms are unresolved. This study analyses the role of alterations in soluble guanylyl cyclase (sGC) in ED.Experimental approachED was analysed in adult male C57BL/6J mice subjected to the Chronic Intermittent Ethanol (CIE) paradigm. Erectile function was assessed in anaesthetised mice in vivo by evaluating intracavernosal pressure (ICP) and in vitro in isolated mice corpora cavernosa (CC) mounted in a myograph. Protein expression and reactive oxygen species were analysed by western blot and dihydroethidium staining, respectively.Key resultsIn CIE mice, we observed a significant decrease in the relaxant response of the CC to stimulation of NO release from nitrergic nerves by electrical field stimulation, to NO release from endothelial cells by acetylcholine, to the PDE5 inhibitor sildenafil, and to the sGC stimulator riociguat. Conversely, the response to the sGC activator cinaciguat, whose action is independent of the oxidation state of sGC, was significantly enhanced in these CC. The responses to adenylyl cyclase stimulation with forskolin were unchanged. We found an increase in reactive oxygen species in the CC from CIE mice as well as an increase in CYP2E1 and NOX2 protein expression. In vivo pre‐treatment with tempol prevented alcohol‐induced erectile dysfunction.Conclusions and implicationsOur results demonstrate that alcoholic mice show ED in vitro and in vivo due to an alteration in the redox state of sGC and suggest that sGC activators may be effective in ED associated with alcoholism.

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“…Bu nedenle çalışmamızda, L-sistein/H2S yolağının mide fundus dokusunda KCl kasılma yanıtları üzerindeki etkisinde NO 'nun rolü araştırıldı. Ayrıca, fare korpus kavernozum 19 ve kobay mesane 20…”

Section: Introductionunclassified

Fare mide fundus dokusunda L-sistein/H2S yolağının KCl kasılma yanıtları üzerindeki etkisine nitrik oksid ve siklooksijenaz yolağının olası katkısı

Aydınoğlu¹

2018

Cukurova Medical Journal

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ÖzPurpose: The aim of present study, was to investigate the effect of L-cysteine/ hydrogen sulfide (H2S) pathway on contractile response to potassium chloride in mouse gastric fundus and possible contributions of nitric oxide (NO) and cyclooxygenase (COX) pathways in this effect Material and Methods: The contractile responses to cumulative KCl was produced in isolated mouse fundus strips and the effect of L-cysteine (10 mM) on this responses was examined. In addition, the effect of Lcysteine on the contractile responses to KCI were investigated in the presence cystathionine beta-synthase (CBS) enzyme inhibitor aminoxyacetic acid (AOAA; 1 mM) and cystathionine gamma-lyase (CSE) enzyme inhibitor propargyl glycine (PAG, 10 mM), which mediated the endogenously synthesize of H2S. The possible contribution of NO and COX pathways to the effect of L-cysteine on KCl contractions was examined in the presence of L-Nitroarginine (L-NA; 0.1 mM), a nitric oxide synthase inhibitor and indomethacin (0.001 M), a non-selective COX inhibitor. Results: The inhibitory effect of L-cysteine on contractile response was significantly reversed by AOAA. However, PAG reduced the inhibitory effect of L-cysteine on the contractile responses to lower concentrations KCl. In the presence of L-NA, L-cysteine decreased the maximum contractile response to KCl and this inhibitory effect was reversed by AOAA and PAG. The inhibitory effect of Lcysteine on the contractile response to lower concentration of KCl was reversed with indomethacin. Conclusion: The findings of current study suggest that Lcystein/H2S pathway has an inhibitory effect on the contractile response to KCl and this effect may be related NO and COX pathways. Amaç: Çalışmamızda, fare mide fundus dokusunda Lsistein/hidrojen sülfür (H2S) yolağının potasyum klorür (KCl) kasılma yanıtları üzerindeki etkisi ve bu etkide nitrik oksid (NO) ve siklooksijenaz (COX) yolaklarının olası katkılarının araştırılması amaçlanmıştır. Gereç ve Yöntem: İzole fare fundus şeritlerinde, kümülatif KCl (10-80 mM) ile kasılma yanıtları oluşturulup, L-sistein (10 mM)'in bu kasılma yanıtları üzerindeki etkisi incelendi. Ayrıca, H2S'in endojen olarak sentezine aracılık eden sistatyon beta-sentaz (CBS) enzim inhibitörü aminooksiasetik asid (AOAA; 1 mM) ve sistatyon gamma-liyaz (CSE) enzim inhibitörü proparjil glisin (PAG, 10 mM) varlığında, L-sistein 'in KCl kasılma yanıtları üzerindeki etkisi araştırıldı. L-sistein'in KCl kasılmaları üzerindeki etkisine NO ve COX yolaklarının olası katkısı, nitrik oksid sentaz (NOS) enzim inhibitörü L-Nitroarjinin (L-NA; 0.1 mM) ve non-selektif COX enzim inhibitörü indometazin (0.001 mM) varlığında incelendi. Bulgular: AOAA, L-sistein'in KCl kasılmaları üzerindeki inhibe edici etkisinin geri çevrilmesine neden oldu. PAG varlığında ise, L-sistein'in düşük konsantrasyonlardaki KCl kasılma yanıtları üzerindeki inhibe edici etkisinin azaldığı gözlendi. L-NA içeren ortamda, L-sistein sadece maksimum KCl kasılma yanıtında bir inhibisyona neden oldu. Bu inhibe edici etki, AOAA ve PAG ile...

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The role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV and Rho-kinase in H 2 S-induced relaxation in the mouse corpus cavernosum

Abstract: These results suggest that PLA, COX, cytochrome P450, PDEIV and Rho-kinase pathway may involve in HS-induced relaxation in mouse corpus cavernosum tissues.

Cited by 9 publications

References 41 publications

Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice

Fare mide fundus dokusunda L-sistein/H2S yolağının KCl kasılma yanıtları üzerindeki etkisine nitrik oksid ve siklooksijenaz yolağının olası katkısı

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