Minocycline attenuates cirrhotic cardiomyopathy and portal hypertension in a rat model: Possible involvement of nitric oxide pathway

Document Type: Original Article

Authors

1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Toxicology–Pharmacology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, Iran

3 Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Department of Toxicology-Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran

5 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Pharmacology, School of Medicine, International Campous, Tehran University of Medical Sciences, Tehran, Iran

Abstract

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 CCl4-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 (50 mg/kg/day for 8 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.

Keywords


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