Minocycline attenuates cirrhotic cardiomyopathy and portal hypertension in a rat model: Possible involvement of nitric oxide pathway
- سال انتشار: 1395
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 19، شماره: 11
- کد COI اختصاصی: JR_IJBMS-19-11_011
- زبان مقاله: انگلیسی
- تعداد مشاهده: 243
نویسندگان
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
چکیده
Objective(s): An increase in nitric oxide (NO) production has been reported in cirrhotic cardiomyopathy and, portal hypertension. Since minocycline has been shown to inhibit NO overproduction, we aimed to examine its role in a rat model of CCl۴-induced cirrhotic cardiovascular complications. Materials and Methods: Portal pressure and inotropic responsiveness of isolated papillary muscles to isoproterenol were measured in cirrhotic rats, following minocycline (۵۰ mg/kg/day for ۸ weeks) treatment. Moreover, isolated papillary muscles were incubated with nonselective and selective nitric oxide synthase (NOS) inhibitors, N (ω)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) respectively, in an organ bath. Ventricular expression and localization of inducible NOS (iNOS), tumor necrosis factor-alpha (TNF-α) and serum nitrite concentration were evaluated. Results: We found a decreased portal hypertension in minocycline-treated cirrhotic rats. Cirrhosis decreased contractility in response to isoproterenol stimulation, which was significantly attenuated by minocycline. Incubation with either L-NAME or AG reversed the impaired contractility in cirrhotic rats. Furthermore, minocycline decreased iNOS expression and localization in cardiomyocytes. A drop in serum nitrite and cardiac TNF-α level were also observed in cirrhotic rat that were treated by minocycline. Conclusion: The results suggest that minocycline may improve impaired cardiac contractility and hyperdynamic state in cirrhotic rats, and this effect could be mediated by NO-dependent mechanism.کلیدواژه ها
Cirrhotic cardiomyopathy Minocycline, Nitric oxide, Portal Hypertension, Ratاطلاعات بیشتر در مورد COI
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