2022

17β-Estradiol inhibites nitric oxide-cGMP-dependent pathway but may activate independent pathway in small intestinum of ovariectomized rat

Bu çalışmada ovaryumları çıkarılmış sıçanlarda 17β-östradiolün ince bağırsak kasılımları üzerine etkisi ile bu etkinin ortaya çıkmasında nitrik oksitin rolü incelenmiştir. Bu amaçla çalışmada 3-6 aylık ve ortalama 270±20 g ağırlığında, 24 Sprague Dawley dişi sıçan her grupta 6 sıçan bulunacak şekilde, kontrol (Ov) ve 3 deneme grubu olmak üzere 4 gruba ayrılmıştır. Çalışmada kontrol grubuna günlük olarak kas içi susam yağı enjeksiyonu yapılmış (0,2 ml), deneme gruplarına sırasıyla 25, 50 ve 100 μg/sıçan 17β-östradiol, üç gün uygulanmıştır. Son uygulamadan 18 saat sonra genel anestezisi altında ötenazi yapılmıştır. Takibinde ince bağırsak, duodenum, jejenum ve ileum bölgelerine ayrılmış ve in vitro izometrik düz kas hareketleri kaydedilmiştir. 17β-östradiolün 50 ve 100 μg/sıçan dozları spontan ileum kasılımlarının gerimini azaltırken duodenumda aynı etkiyi 100 μg/sıçan dozunun oluşturdu gözlemlendi. Jejenumda ise gruplar arasında farklılık oluşmadığı görüldü. Buna karşın L-arjinine (10-5M), 8-Br-cGMP (10-6M) ve SNP (10-3M) uygulamaları duodenum, jejenum ve ileumda spontan düz kas kasılımlarını azalttı. Ayrıca 17β-östradiol uygulamasının L-arjinin ve 8-Br-cGMP’nin gevşetici etkisini azalttığı tersine SNP’nin etkinliğini ise doza bağımlı olarak arttırdığı gösterildi. Sonuç olarak 17β-östradiolün duodenum ve ileumda özellikle cGMP-PK etkinliğini engellemesine rağmen gevşetici etkiye sahip olduğu buna karşın 17β-östradiol aracılığıyla endojen NO-NOS yolunun bağırsağın sekresyon ve/veya siliyar etkinliklerinde rol oynayabileceği önerilmektedir.

17β Östradiol overioktomize sıçanların ince bağırsağında nitrik oksit-cGMP’den bağımsız yolu etkinleştiriyor olabilirken bağımlı yolu engelliyor

This study was designed to investigate the effect of 17β-estradiol on small intestinal motility of ovariectomized rats and the possible role of nitric oxide (NO) in this activity. A total of 24, 3 to 6 month-old female Sprague Dawley rats (270±20 g) were ovariectomized and divided into four groups as one control and three experimental groups. The control group received 0.2 mL, sesame oil once daily for three days, whereas the experimental groups were treated with 25, 50 and 100 μg/rat intramuscular 17β-estradiol, respectively. The rats were sacrificed by cervical dislocation under anaesthesia 18 h after the termination of last treatment. Immediately, duodenum, jejunum and ileum were isolated for organ bath contractility experiments to evaluate isometric smooth muscle motility in vitro. It was observed that application of 100 μg/rat 17β-estradiol showed a decreasing tension in duodenum, whereas none of the different doses of 17β-estradiol showed any significant difference in jejunum. The application of 50 and 100 μg/rat 17β-estradiol decreased the spontaneous contractile tension of ileum. However, L-arginine (10-5M), 8-Br-cGMP (10-6) and SNP (10-3M) decreased the spontaneous contractions of smooth muscle of duodenum, jejunum and ileum. Moreover, it was demonstrated that 17β-estradiol decreased the relaxing activity of L-arginine and 8-Br-cGMP but increased the activity of SNP in dose dependent manner. In conclusion, it is suggested that 17β-estradiol has a relaxative effect in duodenum and ileum and particulary inhibits the activity of cGMP-PK. However, endogenous NO-NOS pathway mediated by 17β-estradiol may play a key role in secretory and/or ciliary activity of intestinum.

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