TY - JOUR T1 - THE EFFECT OF NITRIC OXIDE SYNTHASE ON BETA 3 ADRENOCEPTOR MEDIATED RELAXATION IN STZ DIABETIC RAT HEART TT - STZ DİABETİK SIÇAN KALBİNDE BETA 3 ADRENOSEPTÖR ARACILI GEVŞEME YANITINDA NİTRİK OKSİT SENTAZIN ETKİSİ AU - Arıoğlu İnan, Ebru AU - Kaykı Mutlu, Gizem AU - Karaömerlioğlu, İrem PY - 2019 DA - January Y2 - 2019 DO - 10.33483/jfpau.519948 JF - Journal of Faculty of Pharmacy of Ankara University JO - J. Fac. Pharm. Ankara PB - Ankara University WT - DergiPark SN - 1015-3918 SP - 64 EP - 71 VL - 43 IS - 1 LA - en AB -         Objective: Beta 3 adrenoceptors have been shown to mediatenegative inotropic effect in the heart. In the dibetic rat heart, beta 3adrenoceptor related relaxation response has been found to be augmented. In thepresent study, we aimed to investigate the contribution of nitric oxide andnitric oxide synthase subtypes on beta 3 adrenoceptor mediated relaxationresponse in chronic STZ diabetic rat heart.        Material and Method: 8-week old sprague dawley rats wereused in the study. Diabetes was induced by single dose streptozotocin injection.Some of the diabetic rats were treated with insulin. Beta 3 adrenoceptormediated negative inotropic effect was evaluated by using CL 316,243 in theabsence and presence of L-NAME. The expression of beta 3 adrenoceptor, eNOS,phosphorylated eNOS and nNOS were determined by western blot experiments.        Result and Discussion: The relaxation response was increased in diabetic heart and notnormalized after insulin treatment. The effect was abolished after L-NAMEincubation. Beta 3 adrenoceptor was upregulated in diabetic heart and reachedto control values after treatment. Expression of eNOS, phosphorylated eNOS ornNOS was not altered significantly among the groups. The results of the studyindicate that beta 3 adrenoceptor mediated relaxation in diabetic heart isnitric oxide related. KW - Diabetes KW - heart KW - beta 3 adrenoceptor KW - nitric oxide synthase N2 - Amaç: Beta 3 adrenoseptörlerin kalptenegatif inotropik etkiye aracılık ettiği gösterilmiştir. Diabetik sıçankalbinde, beta 3 adrenoseptör aracılı gevşeme yanıtının belirgin hale geldiğibulunmuştur. Bu çalışmada, kronik STZ diabetik sıçan kalbinde nitrik oksit venitrik oksit sentetaz alttiplerinin beta 3 adrenoseptör aracılı gevşemeyanıtına katkısının araştırılması amaçlanmıştır.        Gereç ve Yöntem: Çalışmada 8-haftalık spraguedawley sıçan kullanılmıştır. Diabet tek doz streptozotosin injeksiyonu ilegerçekleştirilmiştir. Bazı diabetik sıçanlar insulin ile tedavi edilmiştir.Beta 3 adrenoseptör aracılı gevşeme yanıtı CL 316,243 kullanılarak L-NAMEvarlığında ve yokluğunda değerlendirilmiştir. Beta 3 adrenoseptör, eNOS,fosforile eNOS ve nNOS ekspresyonu western blot yöntemi ile ölçülmüştür.        Sonuç ve Tartışma: Diabetik kalpte CL-aracılıgevşeme yanıtları artmıştır, ancak insulin tedavisi sonrasında kontrol düzeyinegelmemiştir. Gözlenen etki L-NAME inkübasyonu sonrasında ortadan kalkmıştır.Beta 3 adrenoseptör ekspresyonu diabetik kalpte artmıştır ve tedavi sonrasıkontrol seviyesine geri dönmüştür. eNOS, fosforile eNOS ve nNOS düzeylerigruplararasında anlamlı bir fark bulunamamıştır. Çalışmanın sonuçları, diabetiksıçan kalbinde beta 3 adrenoseptör aracılı gevşeme yanıtının nitrik oksitbağlantılı olduğunu ortaya koymaktadır.     CR - Harms, H.H., Zaagsma, J., van der Wal, B. (1974). Beta-adrenoceptor studies. III. on the beta-adrenoceptors in rat adipose tissue. European Journal of Pharmacology, 25, 87-97. CR - Gauthier, C., Tavernier, G., Charpentier, F., Langin, D, Le Marec, H. (1996). Functional beta 3 adrenoceptor in the human heart. Journal of Clinical Investigation, 98, 556–562. CR - Gauthier, C., Leblais, V., Kobzik, L., Trochu, J.N., Khandoudi, N., Bril, A., Balligand, J. L., Le Marec, H. (1998). The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. The Journal of Clinical Investigation, 102, 1377-1384. CR - Gauthier, C., Tavernier, G., Trochu, J.N., Leblais, V., Laurent, K., Langin, D., Escande, D., Le Marec, L. (1999). Interspecies differences in the cardiac negative inotropic effects of ß3-adrenoceptor agonists. Journal of Pharmacology Experimental Therapeutics, 290, 687-693. CR - Moniotte, S., Kobzik, L., Feron, O., Trochu, J.N., Gauthier, C., Balligand, J.L. (2001). Upregulation of ß3-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium. Circulation, 103, 1649-1655. CR - Dinçer, Ü.D., Bidasee, K.R., Güner, Ş., Tay, A., Özçelikay, A.T., Altan, V.M. (2001). The effect of diabetes on expression of β1-, β2-, and β3-adrenoreceptors in rat hearts. Diabetes, 50, 455-461. CR - Amour, J., Loyer, X., Le Guen, M., Mabrouk, N., David, J.S., Camors, E., Carusio, N., Vivien, B., Andriantsitohaina, R., Heymes, C., Riou, B. (2007). Altered contractile response due to increased β3-adrenoceptor stimulation in diabetic cardiomyopathy. The role of nitric oxide synthase 1–derived nitric oxide. Anesthesiology, 107, 452-460. CR - Farah, C., Michel, L.Y.M., Balligand, J.L. (2018). Nitric oxide signalling in cardiovascular health and disease. Nature Reviews Cardiology, 15, 292. CR - Kayki-Mutlu, G., Arioglu-Inan, E., Ozakca, I., Ozcelikay, A.T., Altan, V.M. (2014). b3-Adrenoceptor-mediated responses in diabetic rat heart. General Physiology Biophysics, 33, 99-109. CR - Arioglu, E., Guner, S., Ozakca, I., Altan, V.M., Ozcelikay, A.T. (2010). The changes in β-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac β3-adrenoceptors. Molecular and Cellular Biochemistry, 335, 59-66. UR - https://doi.org/10.33483/jfpau.519948 L1 - https://dergipark.org.tr/en/download/article-file/637895 ER -