Salt controls endothelial and vascular phenotype

Abstract

High salt (NaCl) intake promotes the development of vascular diseases independent of a rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. This article summarizes our current understanding of the molecular mechanisms of high salt-induced alterations of the endothelial phenotype, the impact of the individual endothelial genotype, and the overall vascular phenotype. We focus on the endothelial Na(+) channel (EnNaC)-controlled nanomechanical properties of the endothelium, since high Na(+) leads to an EnNaC-induced Na(+)-influx and subsequent stiffening of endothelial cells. The mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function. However, interindividual differences exist in the response to high salt intake which involves different endothelial genotypes. Thus, selected genes and genetic variants contributing to the development of salt-induced endothelial dysfunction and hypertension are discussed. In this review, we focus on the role of salt in endothelial and vascular (dys)function and the link between salt-induced changes of the endothelial and vascular phenotype and its clinical implications.

Impact of Diabetes on Extracellular Volume Status in Patients Initiating Peritoneal Dialysis

“…However, this was a relatively small study and underpowered to determine whether there were similar differences in diabetic patients. Diabetic patients are recognised to be at risk of arterial calcification, and more recently sodium deposition in the vasculature [19,20]. …”

Mechanisms Underlying Enhanced Noradrenaline-Induced Femoral Arterial Contractions of Spontaneously Hypertensive Rats: Involvement of Endothelium-Derived Factors and Cyclooxygenase-Derived Prostanoids

“…By contrast, contractions induced by beraprost (a stable PGI 2 analogue), PGE 2 , and U46619 (thromboxane/prostanoid receptor agonist) were similar between the SHR and WKY groups. Thus, NAdinduced femoral arterial contractions are augmented in SHR resulting from endothelial dysfunction and increased COX-derived vasoconstrictor prostanoid levels.Key words cyclooxygenase; endothelium; femoral artery; hypertension; contraction Hypertension is one of the most common chronic diseases in humans, 1) and hypertension-associated vascular complications such as stroke, heart failure, kidney diseases and peripheral arterial diseases are major sources of morbidity and mortality that exacerbate the quality of life.1-3) Because dysfunction and abnormal signaling in the main structural elements of the vasculature, such as endothelial cells and smooth muscle cells, are characteristic hypertension-associated vascular complications, [4][5][6][7][8][9] and functional impairments in these cells are observed in hypertensive patients and animal models of the disease, 10-19) a comprehensive understanding of the underlying mechanisms is indispensable for preventing and treating such complications.Among endothelium-derived factors, nitric oxide (NO) is of the greatest importance for modulating vascular function. 20,21) However, other factors including endothelium-derived hyperpolarizing factor (EDHF) and cyclooxygenase (COX)-derived prostanoids can also modulate vascular tone.…”

“…[1][2][3] Because dysfunction and abnormal signaling in the main structural elements of the vasculature, such as endothelial cells and smooth muscle cells, are characteristic hypertension-associated vascular complications, [4][5][6][7][8][9] and functional impairments in these cells are observed in hypertensive patients and animal models of the disease, [10][11][12][13][14][15][16][17][18][19] a comprehensive understanding of the underlying mechanisms is indispensable for preventing and treating such complications.…”

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