RESUMEN
The present review will focus on the role of chloride anion in cardiovascular disease, with special emphasis in the development of hypertensive disease and vascular inflammation. It is known that acute and chronic overload of sodium chloride increase blood pressure and have pro-inflammatory and pro-fibrotic effects on different target organs, but it is unknown how chloride may influence these processes. Chloride anion is the predominant anion in the extracellular fluid and its intracellular concentration is dynamically regulated. As the queen of the electrolytes, it is of crucial importance to understand the physiological mechanisms that regulate the cellular handling of this anion including the different transporters and cellular chloride channels, which exert a variety of functions, such as regulation of cellular proliferation, differentiation, migration, apoptosis, intracellular pH and cellular redox state. In this article, we will also review the relationship between dietary, serum and intracellular chloride and how these different sources of chloride in the organism are affected in hypertension and their impact on cardiovascular disease. Additionally, we will discuss the approach of potential strategies that affect chloride handling and its potential effect on cardiovascular system, including pharmacological blockade of chloride channels and non-pharmacological interventions by replacing chloride by another anion.
Asunto(s)
Canales de Cloruro/metabolismo , Cloruros/metabolismo , Hipertensión/etiología , Animales , Humanos , Hipertensión/metabolismoRESUMEN
RESUMEN Introducción: Se desconoce el papel del anión cloruro en los efectos deletéreos del consumo excesivo de sal (NaCl) y si sus efectos son independientes de la presencia del sodio. Objetivo: Demostrar que tanto una sobrecarga de cloruro como una sobrecarga de sodio en la dieta producen efectos deletéreos, en forma independiente, sobre la presión arterial sistólica (PAS), la función renal y los marcadores de estrés oxidativo en el riñón. Materiales y métodos: Ratas Wistar macho fueron divididas en cuatro grupos (n = 8/grupo) y fueron alimentadas con diferentes dietas durante tres semanas: C: control (dieta estándar), NaCl: hipersódica-hiperclórica, Na: hipersódica sin cloruro, Cl: hiperclórica sin sodio. Se determinaron la presión arterial sistólica (PAS) y la función renal y en la corteza renal, se evaluó la producción de especies reactivas del ácido tiobarbitúrico (en inglés: TBARS) y la actividad y la expresión de las enzimas superóxido dismutasa (SOD), catalasa (CAT) y glutatión peroxidasa (GPx). Resultados: Al cabo de tres semanas, la PAS aumentó (*) en los dos grupos alimentados con cloruro. La excreción fraccional de sodio y de cloruro aumentó (*) en los grupos NaCl y Na. La diuresis y los TBARS en la corteza renal aumentaron (*) con las tres dietas, sin cambios en la actividad y en la expresión de SOD y CAT. La actividad de la GPx aumentó (*) en los dos grupos que recibieron cloruro; (*p < 0,05 vs C). Conclusión: Tanto la sobrecarga de sodio como la de cloruro se asocian a mayor estado oxidativo caracterizado por un incremento en la peroxidación lipídica en la corteza renal. Sin embargo, solo el exceso de cloruro se asocia a mayor actividad de la GPx y de la hipertensión, sin cambios en la excreción urinaria de cloruros, sugiriendo un mayor estado prooxidante renal en comparación con el grupo Na.
ABSTRACT Introduction: The role of the chloride anion on the deleterious effects of excessive consumption of salt (NaCl) and whether its effects are independent each other of the presence of sodium remains to date, unknown and unclear. Objective: To demonstrate that both a chloride overload and a sodium overload in the diet produce deleterious effects, by different mechanisms, on systolic blood pressure (SBP), renal function and markers of oxidative stress in the kidney. Materials and Methods: Male Wistar rats were divided into four groups (n = 8 / group) and fed with different diets for three weeks: C: control (standard diet), and diets: NaCl: hypersodic-hyperchloric; Na: hypersodic without chloride and Cl: hyperchloric without sodium. Systolic blood pressure (SBP) and renal function were determined, and the production of thiobarbituric acid reactive species (TBARS) and the activity and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were evaluated in renal cortex tissue. Results: SBP increased (*) in the two groups fed with chloride. The fractional excretion of sodium and chloride increased (*) in the NaCl and Na groups. increased (*) in the renal cortex with the three diets. No changes were observed in the activity and expression of SOD and CAT. GPx activity increased (*) in the two groups that received chloride; (* p <0.05 vs C). Conclusion: Both sodium and chloride overload are associated with a higher oxidative state characterized by an increase in lipid peroxidation in the renal cortex. However, compared with Na group, only chloride overload is associated with higher GPx activity and hypertension without any changes in urinary chloride excretion, suggesting a higher renal pro-oxidant state in this experimental group.