4.6 Review

Kidney and blood pressure regulation-latest evidence for molecular mechanisms

Journal

CLINICAL KIDNEY JOURNAL
Volume 16, Issue 6, Pages 952-964

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/ckj/sfad015

Keywords

blood pressure regulation; hypertension; renin-angiotensin-aldosterone system (RAAS); renal salt transport

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Hypertension is a major health issue related to cardiovascular diseases, with complex molecular mechanisms involving multiple factors. Salt intake is a leading determinant of blood pressure, and the kidney plays a major role in maintaining blood pressure. This review provides an overview of the molecular mechanisms of blood pressure modulation associated with renal ion channels/transporters, and highlights the potential for novel therapeutic approaches based on recent studies in animal models.
Hypertension is one of the major health problems leading to the development of cardiovascular diseases. Despite a rapid expansion in global hypertension prevalence, molecular mechanisms leading to hypertension are not fully understood largely due to the complexity of pathogenesis involving several factors. Salt intake is recognized as a leading determinant of blood pressure, since reduced dietary salt intake is related to lower morbidity and mortality, and hypertension in relation to cardiovascular events. Compared with salt-resistant populations, salt-sensitive individuals exhibit high sensitivity in blood pressure responses according to changes in salt intake. In this setting, the kidney plays a major role in the maintenance of blood pressure under the hormonal control of the renin-angiotensin-aldosterone system. In the present review, we summarize the current overview on the molecular mechanisms for modulation of blood pressure associated with renal ion channels/transporters including sodium-hydrogen exchanger isoform 3 (NHE3), Na+-K+-2Cl(-) cotransporter (NKCC2), sodium-chloride cotransporter (NCC), epithelial sodium channel (ENaC) and pendrin expressed in different nephron segments. In particular, recent studies on experimental animal models with deletion of renal ion channels led to the identification of several crucial physiological mechanisms and molecules involved in hypertension. These findings could further provide a potential for novel therapeutic approaches applicable on human patients with hypertension.

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