Year: 2012
Type: review
Abstract: Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na(+) ). We recently identified two novel mechanisms that impair renal Na(+) -excreting function and result in an increase in BP. First, mineralocorticoid receptor (MR) activation in the kidney, which facilitates distal Na(+) reabsorption through epithelial Na(+) channel activation, causes salt-sensitive hypertension. This mechanism exists not only in models of high-aldosterone hypertension as seen in conditions of obesity or metabolic syndrome, but also in normal- or low-aldosterone type of salt-sensitive hypertension. In the latter, Rac1 activation by salt excess causes MR stimulation. Second, renospecific sympathoactivation may cause an increase in BP under conditions of salt excess. Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension. Abnormalities identified in these two pathways of Na(+) reabsorption in the distal nephron may present therapeutic targets for the treatment of salt-sensitive hypertension.
Source: Annals of Medicine
Authors: Katsuyuki Ando, Toshiro Fujita
Institution: The University of Tokyo
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Evaluation of the mechanisms to progress hypertension and kidney injury in high fat loading during young age, Epigenetic mechanisms underlying renal derangement in hypertension and diabetes, The mechanism for activation of aldosterone/mineralocorticoid receptor in life style-related diseases
OpenAlex ID: W1983090164