Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats
Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction which is known as cirrhotic cardiomyopathy. Cardiac responsiveness to adrenergic stimulation is impaired in cirrhosis. Moreover, there is vagal nerve dysfunction which is related to neuromodulatory dysfunction of the angiote...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tehran University of Medical Sciences
2018-02-01
|
| Series: | Acta Medica Iranica |
| Subjects: | |
| Online Access: | https://acta.tums.ac.ir/index.php/acta/article/view/6351 |
| _version_ | 1818208625680711680 |
|---|---|
| author | Farahnaz Jazaeri Razieh Afsharmoghaddam Alireza Abdollahi Giti Ghamami Ahmad Reza Dehpour |
| author_facet | Farahnaz Jazaeri Razieh Afsharmoghaddam Alireza Abdollahi Giti Ghamami Ahmad Reza Dehpour |
| author_sort | Farahnaz Jazaeri |
| collection | DOAJ |
| description | Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction which is known as cirrhotic cardiomyopathy. Cardiac responsiveness to adrenergic stimulation is impaired in cirrhosis. Moreover, there is vagal nerve dysfunction which is related to neuromodulatory dysfunction of the angiotensin II in the cirrhosis. This study was aimed to explore the hypothesis that administration of Losartan-angiotensin II receptor antagonist increases cardiac chronotropic response to isoproterenol in cirrhotic rats; and if so, whether this is associated with altered cardiac TGF-β receptor expression. Cirrhosis was induced by surgical ligation of the bile duct (BDL) in male Wister rats. Half of the BDL-group and control group were treated with losartan for four weeks. Four weeks after bile duct ligation or sham surgery the atria were isolated and spontaneously beating rate and chronotropic responsiveness to β-adrenergic stimulation was assessed using standard organ bath. The pathological assessment was done on the atria. Moreover, the expression of TGF-β has assessed the atria using quantitative RT-PCR. Bile duct ligation could induce a significant hypo-responsiveness to adrenergic stimulation. In cirrhotic rats, the chronotropic responses increased after chronic treatment with losartan, but it was not significant. The pathological study showed that losartan could not decrease fibrosis in atria in losartan treated cirrhotic group. TGF-β expression is markedly increased in cirrhotic rats which are significantly decreased in atria following administration of losartan. These results might be considered as angiotensin II role in cirrhotic cardiomyopathy, but further studies are required to elaborate the mechanism as well as the possible advantage of losartan. We conclude that cirrhosis in rats is associated with altered expression of TGF-β in the atrium which losartan can ameliorate it. |
| first_indexed | 2024-12-12T04:47:48Z |
| format | Article |
| id | doaj.art-78c45a923a9f4fd9bc6e394fcdbf6464 |
| institution | Directory Open Access Journal |
| issn | 0044-6025 1735-9694 |
| language | English |
| last_indexed | 2024-12-12T04:47:48Z |
| publishDate | 2018-02-01 |
| publisher | Tehran University of Medical Sciences |
| record_format | Article |
| series | Acta Medica Iranica |
| spelling | doaj.art-78c45a923a9f4fd9bc6e394fcdbf64642022-12-22T00:37:34ZengTehran University of Medical SciencesActa Medica Iranica0044-60251735-96942018-02-015615249Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic RatsFarahnaz Jazaeri0Razieh Afsharmoghaddam1Alireza Abdollahi2Giti Ghamami3Ahmad Reza Dehpour4Department 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 Pathology, 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 Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction which is known as cirrhotic cardiomyopathy. Cardiac responsiveness to adrenergic stimulation is impaired in cirrhosis. Moreover, there is vagal nerve dysfunction which is related to neuromodulatory dysfunction of the angiotensin II in the cirrhosis. This study was aimed to explore the hypothesis that administration of Losartan-angiotensin II receptor antagonist increases cardiac chronotropic response to isoproterenol in cirrhotic rats; and if so, whether this is associated with altered cardiac TGF-β receptor expression. Cirrhosis was induced by surgical ligation of the bile duct (BDL) in male Wister rats. Half of the BDL-group and control group were treated with losartan for four weeks. Four weeks after bile duct ligation or sham surgery the atria were isolated and spontaneously beating rate and chronotropic responsiveness to β-adrenergic stimulation was assessed using standard organ bath. The pathological assessment was done on the atria. Moreover, the expression of TGF-β has assessed the atria using quantitative RT-PCR. Bile duct ligation could induce a significant hypo-responsiveness to adrenergic stimulation. In cirrhotic rats, the chronotropic responses increased after chronic treatment with losartan, but it was not significant. The pathological study showed that losartan could not decrease fibrosis in atria in losartan treated cirrhotic group. TGF-β expression is markedly increased in cirrhotic rats which are significantly decreased in atria following administration of losartan. These results might be considered as angiotensin II role in cirrhotic cardiomyopathy, but further studies are required to elaborate the mechanism as well as the possible advantage of losartan. We conclude that cirrhosis in rats is associated with altered expression of TGF-β in the atrium which losartan can ameliorate it.https://acta.tums.ac.ir/index.php/acta/article/view/6351CardiomyopathyCirrhosisLosartanTGF-β |
| spellingShingle | Farahnaz Jazaeri Razieh Afsharmoghaddam Alireza Abdollahi Giti Ghamami Ahmad Reza Dehpour Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats Acta Medica Iranica Cardiomyopathy Cirrhosis Losartan TGF-β |
| title | Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats |
| title_full | Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats |
| title_fullStr | Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats |
| title_full_unstemmed | Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats |
| title_short | Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats |
| title_sort | evaluation of chronic losartan treatment effect on cardiac chronotropic dysfunction in biliary cirrhotic rats |
| topic | Cardiomyopathy Cirrhosis Losartan TGF-β |
| url | https://acta.tums.ac.ir/index.php/acta/article/view/6351 |
| work_keys_str_mv | AT farahnazjazaeri evaluationofchroniclosartantreatmenteffectoncardiacchronotropicdysfunctioninbiliarycirrhoticrats AT raziehafsharmoghaddam evaluationofchroniclosartantreatmenteffectoncardiacchronotropicdysfunctioninbiliarycirrhoticrats AT alirezaabdollahi evaluationofchroniclosartantreatmenteffectoncardiacchronotropicdysfunctioninbiliarycirrhoticrats AT gitighamami evaluationofchroniclosartantreatmenteffectoncardiacchronotropicdysfunctioninbiliarycirrhoticrats AT ahmadrezadehpour evaluationofchroniclosartantreatmenteffectoncardiacchronotropicdysfunctioninbiliarycirrhoticrats |