RESUMO
AIM: To examine the interference of ß-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), ß-arrestins (ß1-AR and ß2-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 ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-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.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Movimento Celular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Atenolol/farmacologia , Carbazóis/farmacologia , Carvedilol , Quimiocina CXCL12/sangue , Modelos Animais de Doenças , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Hipertensão/sangue , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Metoprolol/farmacologia , Miocárdio/metabolismo , NF-kappa B/metabolismo , Propanolaminas/farmacologia , Propranolol/farmacologia , Ratos Endogâmicos SHR , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta-Arrestina 1/metabolismo , beta-Arrestina 2/metabolismoRESUMO
Hypertensive patients have a higher risk of developing health complications, particularly cardiovascular (CV) events, than individuals with normal blood pressure (BP). Severity of complications depends on the magnitude of BP elevation and other CV risk factors associated with the target organ damage. Therefore, BP control and management of organ damage may contribute to reduce this risk. BP variability (BPV) has been considered a physiological marker of autonomic nervous system control and may be implicated in increased CV risk in hypertension. This review will present some evidence relating BPV and target organ damage in hypertension in clinical and experimental settings.
Assuntos
Pressão Sanguínea , Hipertensão/fisiopatologia , Animais , Anti-Hipertensivos/uso terapêutico , Sistema Nervoso Autônomo/fisiopatologia , Determinação da Pressão Arterial , Humanos , Hipertensão/tratamento farmacológico , Fatores de RiscoRESUMO
Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30µgkg(-1)day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1-7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.