Comparative cardioprotective effects of carvedilol versus atenolol in a rat model of cardiorenal syndrome type 4

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2021-10, Vol.394 (10), p.2117-2128
• Main Authors: Mohamed, Rasha M. S. M., Elshazly, Shimaa M., Nafea, Ola E., Abd El Motteleb, Dalia M.
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Atenolol; Atenolol - pharmacology; Atenolol - therapeutic use; beta-Arrestin 2 - metabolism; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Brain natriuretic peptide; Cardio-Renal Syndrome - drug therapy; Cardio-Renal Syndrome - metabolism; Cardio-Renal Syndrome - physiopathology; Cardio-Renal Syndrome - surgery; Cardiomegaly - drug therapy; Cardiomegaly - metabolism; Cardiomegaly - physiopathology; Cardiomegaly - surgery; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Carvedilol - pharmacology; Carvedilol - therapeutic use; Caspase-3; Diacylglycerol Kinase - metabolism; Diglycerides; Disease Models, Animal; Drinking water; Health care; Heart; Hypertrophy; Inositol; Kidney - drug effects; Kidney - physiology; Kidney diseases; Kinases; Male; Morbidity; Myocardium - metabolism; Nephrectomy; Neurosciences; Original Article; Pharmacology/Toxicology; Phosphatidylinositol 4,5-diphosphate; Phosphatidylinositol 4,5-Diphosphate - metabolism; Rats; Rats, Wistar; Receptors, Adrenergic, beta-1 - metabolism
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-021-02130-1

The incidence of chronic kidney disease is escalating; cardiorenal syndrome (CRS) type 4 is gaining a major health concern causing significant morbidity and mortality, putting major burdens on the healthcare system. This study was designed to compare the cardioprotective effects of carvedilol versus atenolol against CRS type 4 induced by subtotal 5/6 nephrectomy in rats and to explore the underlying mechanisms. Immediately after surgery, carvedilol (20 mg/kg/day) or atenolol (20 mg/kg/day) was added to drinking water for 10 weeks. Carvedilol was more effective than atenolol in improving kidney functions, decreasing elevated blood pressures, attenuating cardiac hypertrophy, reducing serum brain natriuretic peptide, and diminished cardiac fibrous tissue deposition. However, carvedilol was equivalent to atenolol in modulating β 1 -adrenergic receptors (β 1 ARs) and cardiac diacylglycerol (DAG) signaling, but carvedilol was superior in modulating β-arrestin2, phosphatidyl inositol 4,5 bisphosphates (PIP2), and caspase 3 levels. Carvedilol has superior cardioprotective effects than atenolol in a rat model of CRS type 4. These protective effects are mediated through modulating cardiac β 1 ARs/β-arrestin2/PIP2/DAG as well as abating cardiac apoptotic signaling pathways (caspase3/pS473 protein kinase B (Akt)).