Role of GRK5/β-arrestin2 pathway in mediating the cardioprotective effects of carvedilol in 5/6 nephrectomized rats
Mohamed, R., Elshazly, S., Salem, A., Mahmoud, N. (2022). Role of GRK5/β-arrestin2 pathway in mediating the cardioprotective effects of carvedilol in 5/6 nephrectomized rats. EKB Journal Management System, 28(1), 163-173. doi: 10.21608/zumj.2021.77150.2238
Rasha Mohamed; Shimaa Elshazly; Amal E Salem; Nevertyty Mahmoud. "Role of GRK5/β-arrestin2 pathway in mediating the cardioprotective effects of carvedilol in 5/6 nephrectomized rats". EKB Journal Management System, 28, 1, 2022, 163-173. doi: 10.21608/zumj.2021.77150.2238
Mohamed, R., Elshazly, S., Salem, A., Mahmoud, N. (2022). 'Role of GRK5/β-arrestin2 pathway in mediating the cardioprotective effects of carvedilol in 5/6 nephrectomized rats', EKB Journal Management System, 28(1), pp. 163-173. doi: 10.21608/zumj.2021.77150.2238
Mohamed, R., Elshazly, S., Salem, A., Mahmoud, N. Role of GRK5/β-arrestin2 pathway in mediating the cardioprotective effects of carvedilol in 5/6 nephrectomized rats. EKB Journal Management System, 2022; 28(1): 163-173. doi: 10.21608/zumj.2021.77150.2238

Role of GRK5/β-arrestin2 pathway in mediating the cardioprotective effects of carvedilol in 5/6 nephrectomized rats

Zagazig University Medical Journal
Article 19, Volume 28, Issue 1, January 2022, Page 163-173  XML PDF (1.03 MB)
Document Type: Original Article
DOI: 10.21608/zumj.2021.77150.2238
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Authors
Rasha Mohamed email orcid 1; Shimaa Elshazly2; Amal E Salem3; Nevertyty Mahmoud1
1Clinical pharmacology department, Faculty of Medicine, Zagazig University, Egypt
2PHARMACOLOGY AND TOXICOLOGY DEPARTMENT, FACULTY OF PHARMACY
3Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Abstract
Background: Cardiorenal-syndrome is associated with high morbidity and mortality rates. This study tries to clarify the cardio-protective effects of carvedilol in 5/6 nephrectomized rats. Methods: The current study involved five groups of rats: sham, 5/6 nephrectomy, carvedilol (20mg/kg/day, i.p), amlexanox (25mg/kg/day, i.p), and carvedilol + amlexanox groups. Rats were subjected to 5/6 nephrectomy. Just after surgery, drugs were given for 10 weeks. At the end of study, kidney functions, blood pressure, and markers of cardiomyocyte apoptosis and heart failure were measured. Also, cardiac β1-adrenergic receptor signaling was measured. Results: 5/6 nephrectomy caused renal impairment, elevated both systolic and diastolic blood pressure and apoptosis with downregulation of cardiac β-arrestin2 down-stream proteins. On the contrary, carvedilol significantly reduced renal and cardiac deteriorations in 5/6 nephrectomized rats. Moreover, injection of amlexanox prior to carvedilol significantly reduced carvedilol-cardioprotective-effects. Conclusion: Carvedilol-induced cardiac protection in 5/6 nephrectomized rats is highly correlated with upregulation of cardiac G-protein coupled receptor kinase 5/β-arrestin2 pathway.
Keywords
Carvedilol; β-arrestin2; cardiorenal syndrome; amlexanox; G-protein coupled receptor kinase 5(GRK5)
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