β‐blockers interfere with cell homing receptors and regulatory proteins in a model of spontaneously hypertensive rats

• Published in: Cardiovascular therapeutics 2018-08, Vol.36 (4), p.e12434-n/a
• Main Authors: Eibel, Bruna, Kristochek, Melissa, Peres, Thiago R., Dias, Lucinara D., Dartora, Daniela R., Casali, Karina R., Kalil, Renato A. K., Lehnen, Alexandre M., Irigoyen, Maria Claudia, Markoski, Melissa M.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-1 Receptor Antagonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Antihypertensive Agents - pharmacology; Atenolol - pharmacology; beta-Arrestin 1 - metabolism; beta-Arrestin 2 - metabolism; Carbazoles - pharmacology; Carvedilol; Cell Movement - drug effects; Chemokine CXCL12 - blood; Chemokines; Disease Models, Animal; G-Protein-Coupled Receptor Kinase 2 - metabolism; Hypertension; Hypertension - blood; Hypertension - drug therapy; Hypertension - physiopathology; Kidney - drug effects; Kidney - metabolism; Liver - drug effects; Liver - metabolism; Lung - drug effects; Lung - metabolism; Metoprolol - pharmacology; Myocardium - metabolism; NF-kappa B - metabolism; Propanolamines - pharmacology; Propranolol - pharmacology; Proteins; Rats, Inbred SHR; Receptors, CXCR - metabolism; Receptors, CXCR4 - metabolism; Rodents; SDF‐1; Signal Transduction - drug effects; spontaneously hypertensive rats; stem cell homing; β‐blockers
• ISSN: 1755-5914; 1755-5922
• DOI: 10.1111/1755-5922.12434

Aim To examine the interference of β‐blockers with the chemokine stromal cell‐derived factor‐1 (SDF‐1) found in cell homing receptors, C‐X‐C chemokine receptor type 4 (CXCR‐4) and CXCR‐7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. Method We collected blood samples before and after treatment and quantified the levels of SDF‐1 with enzyme‐linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR‐4, CXCR‐7, GRK‐2 (G protein‐coupled receptors kinase 2), β‐arrestins (β1‐AR and β2‐AR), and nuclear factor kappa B (NFκB). Results We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of β1‐AR (P = .0102) and β2‐AR (P = .0034). Conclusion β‐blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.