Effects of chronic low- and high-dose ethanol intake on the nitrergic relaxations of corpus cavernosum and penile nitric oxide synthase in the rabbit

Epidemiological evidence showed that chronic ethanol consumption is a major risk factor in the development of impotence. The present study investigated the effects of carbachol-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)- and papaverine-induced relaxant responses in the isolated corpus cavernosum tissues from rabbits submitted to an 12-week course of chronic low (5% v/v) or high ethanol intake (30% v/v). Increased carbachol- and EFS-induced relaxant responses but not SNP and papaverine, were observed in low ethanol-fed rabbits compared with controls. However, impaired carbachol- and EFS-induced relaxant responses were observed in high ethanol-fed rabbits compared with control rabbits. There were no significant differences in SNP- and papaverine-induced relaxant responses between control and high ethanol-fed rabbits. In addition, decreased neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) immunoreactivity in penile tissue were found in high ethanol-fed rabbits, but increased the immunoreactivity in low ethanol-fed group, compared with control group. These results suggest that alterations in nitric oxide (NO) production within the cavernous tissue in the high ethanol-fed rabbits are, at least in part, responsible for the erectile dysfunction.Kocaeli University Research FundKocaeli University [200319]This study was supported by a grant from Kocaeli University Research Fund (Project number: 200319). Research Foundation had no further role in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication

Investigation of the Functional Responses of Myometrium Smooth Muscle in Secondhand Smoking and Chronic Alcohol Consuming Rats

Gebelik sırasında sigara tüketiminin erken doğum için majör bir risk faktörü olmasına rağmen, sigara tüketiminin uterin kasılmaları stimüle etmesinin altında yatan mekanizma hala tam olarak anlaşılamamıştır. Gebelik sırasında alkol tüketimi gelişme geriliği ve mental yetmezlik gibi fetal teratojenitelerin görülmesine neden olmaktadır. Bununla birlikte alkolün sağlıklı fetal çevre için gerekli myometriyal kasılma ve gevşeme yanıtlarına etkisi çok az bilinmektedir. Bu çalışmanın amacı kronik sigara ve alkol tüketiminin preterm sıçanlardan izole edilen myometriyum şeritlerinin kasılma ve gevşeme yanıtlarının frekans ve amplitüdleri üzerine etkilerinin araştırılmasıdır. Çalışmada 21 adet Wistar albino sıçan kullanıldı. Sıçanlar 3 gruba ayrıldı: 1. Gruba (kontrol) hiçbir uygulama yapılmadı (n=7); 2. Gruptaki sıçanlar 12 hafta boyunca sigara dumanına maruz bırakıldı (n=7); 3 Gruptaki sıçanların içme sularına 12 hafta boyunca alkol eklendi (n=7). Doğum dönemlerinde bulunan kontrol, sigara ve alkol grubu sıçanlardan izole edilen myometriyal şeritler izometrik kayıt almak üzere organ banyosuna yerle?tirildi. Karbakol (10-8 -10-4 M), oksitosin (10-9 -10-3 M) ve diltiazem (10-8 -10-4 M)kümülatif konsantrasyonlarının myometriyal spontan kontraksiyonlar üzerindeki etkileri ölçüldü. Karbakol kasılma yanıtları spontan kasılmaların amplitüd ve frekansı bakımından alkol grubunda anlamlı olarak azalırken, sigara grubunda anlamlı olarak arttı (p<0.05). Oksitosin kasılma yanıtları, alkol grubundan izole edilen myometriyal şeritlerin spontan kasılmalarının amplitüd ve frekansını azalttı (p<0.05). Sigara grubunda oksitosin yanıtları için amplitüd değeri değişmezken, frekans değeri anlamlı olarak azaldı (p<0.05). Diltiazem gevşeme yanıtları amplitüd ve frekans bakımından alkol grubunda başlangıçtan 10-5 M konsantrasyona kadar anlamlı olarak azaldı (p<0.05). Sigara grubunda ise diltiazem yanıtı kontrollerine göre anlamlı olarak farklı bulunmadı. Bu bulgular sigara ve alkol tüketiminin izole myometriyum düz kas kasıcı ve gevşetici yanıtlarına zarar verdiğini ve bu nedenle doğum komplikasyon riskini artırdıklarını desteklemektedir.Although smoking during pregnancy is a major risk factor for preterm delivery, the underlying mechanism by which smoking stimulates uterine contractions is still poorly understood. Maternal consumption of ethanol during pregnancy is associated with the apperarence of fetal teratogenic effects such as growth restriction and mental impairments. However, very littke is known about the effects of alcohol on myometrial relaxant or contractile responses which is essential for healthy fetal environment. The aim of this study was to investigate the effects of chronic smoking and alcohol consumption on the amplitude and frequency of contractile and relaxant responses of preterm myometrial strips isolated from rats. Twenty one Wistar albino rats were divided into three groups. Group 1: Control (n=7), received tap water ad libitum, Group 2: (Smoking) Rats exposed to smoke for 12 weeks (n=7), Group 3:(Alcohol), were fed with ethanol for 12 weeks (n=7). The reactivities of myometrial strips obtained from term labor rats of the smoking, alcohol and the control groups were mounted in organ chambers for recording of isometric tension. The effects of cumulative concentrations of carbachol (10-8 -10-4 M), oxytocin (10-9 -10-3 M) and diltiazem (10-8 -10-4 M) on myometrial spontaneous contractions were measured. Carbachol contractile responses were decreased the amplitude and frequency of spontaneous contractions of myometrial strips in alcohol group, whereas significantly increased in smoking group (p<0.05). Oxytocin contractile responses were decreased the amplitude and frequency of spontaneous contractions of myometrial strips in alcohol group (p<0.05). The frequency of myometrial contraction of oxytocin were significantly increased by smoking (p<0.05), while the amplitude of contractions were not changed. The amplitude and frequency of myometrial relaxations were significantly decreased by alcohol beginning from the concentration of 10-5 M (p<0.05). There were no significant differences between relaxant responses to diltiazem of smoking and control group. These findings suggest that smoking and alcohol consumption impaired contractile and relaxant responses in the isolated myometrial smooth muscles and thereby increases the risk of birth complications

Chronic administration of imipramine but not agomelatine and moclobemide affects the nitrergic relaxation of rabbit corpus cavernosum smooth muscle

Sexual dysfunction is a common and underestimated effect of antidepressants. However, the mechanism by which these drugs cause erectile dysfunction is unclear. We investigated the reactivity of the corpus cavernosum of rabbits that were treated with either chronic imipramine, which is a tricyclic agent; agomelatine, which is a melatonergic agonist and serotonin 5HT(2c) antagonist; or moclobemide, which is a reversible inhibitor of monoamine-oxidase A. Twenty rabbits were randomly divided into four groups: the control group (n = 5), the imipramine-treated group (n = 5), which received i.p. injections of 10 mg/kg/day of imipramine, the moclobemide-treated group (n = 5), which received i.p injections of 20 mg/kg/day of moclobemide, and the agomelatine-treated group (n = 5), which was orally administered 10 mg/kg/day of agomelatine. The reactivities of corpus cavernosum tissue obtained from the antidepressant-treated and the control groups were studied in organ chambers after the animals were subjected to 21 days of drug administration. The acetylcholine-induced endothelium-dependent and the electrical field stimulation (EFS)-induced neurogenic relaxation of the corpus cavernosum of the imipramine-treated group was significantly decreased compared with the control group. However, neither the acetylcholine- nor EFS-induced relaxation was changed in the moclobemide- or agomelatine-treated groups. There were no change in the relaxant response to the nitric oxide (NO) donor sodium nitroprusside and contractile response to KCl between the groups. This study suggests that chronic imipramine treatment but not agomelatine and moclobemide treatments causes significant functional changes in the penile erectile tissue of rabbits and that these changes may contribute to the development of impotence. (c) 2013 Elsevier B.V. All rights reserved

Protective effects of resveratrol in aging-induced cognitive impairment in rats

[No Abstract Available

İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması

Amaç: Bu çalışma son yıllarda tanımlanan imidazolin (I) reseptörlerinin özellikle I2 alt tipine seçici olarak bağlanan maddelerden yararlanarak söz konusu reseptörlerin morfin bağımlılığındaki etkisini araştırmak üzere planlanmıştır. Yöntem: I2 reseptörlerinin agonisti olan 2-BFI ve antagonisti olan BU224 in vivo bağımlılık modellerinde kullanılmıştır. İn vivo bağımlılık Sprague-Dawley sıçanlara ciltaltı morfin peleti (toplam 150 mg) yerleştirilerek oluşturulmuştur. İmplantasyondan 72 saat sonra intraperitoneal (i.p.) olarak 2-BFI (3, 5 veya 10 mg/ kg) veya BU224 (3, 5 veya 10 mg/kg) uygulamasından 30 dakika sonra nalokson (2 mg/kg) enjekte edilerek değerlendirilmiştir. Nalokson uygulamasının hemen ardından sıçanlar 15 dakika boyunca gözlenerek sıçrama, ıslak köpek titremesi, karın germe, defekasyon, pitozis, diş gıcırdatma, diyare, tremor gibi morfin yoksunluğu belirtileri kaydedilmiştir. Bulgular: Hem 2-BFI hem de BU224 naloksonla yoksunluk sendromu oluşturmadan önce uygulandığında yoksunluk semptomlarını doza bağımlı bir biçimde baskılanmıştır. 2-BFI’nın en düşük dozu (3 mg/kg) sıçramada ve BU224’ün en düşük dozu (3 mg/kg) ıslak köpek titremesi ve kilo kaybında etkisiz bulunmuştur. Sonuç: Hem 2-BFI hem de BU224’ün yoksunluk semptomlarını baskıladığı gösterilmiştir. Bu çalışmanın sonuçları I sisteminin belki kısmen reseptörleri aracılığıyla belki de farklı mekanizmaları kullanarak morfin bağımlılığı ve/veya yoksunluğunda önemli rolü olduğunu düşündürmektedir