Genetics of Salt-Sensitive Hypertension

Sanada, Hironobu; Jones, John E.; José, Pedro A.

doi:10.1007/s11906-010-0167-6

Cited by 122 publications

(103 citation statements)

References 139 publications

(244 reference statements)

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“…It has been reported that a number of candidate gene variants, for example, those involved in the renin-angiotensin-aldosterone system and ion channels, are associated with salt sensitivity, 23 although they are difficult to replicate and remain largely inconclusive. 24 Impacts of obesity on hypertension Racial and ethnic differences have also been assumed to exist in terms of the components and impacts of genetic factors for obesity, and traits or disorders related to obesity, for example, type 2 diabetes.…”

Section: Salt Sensitivitymentioning

confidence: 99%

Ethnic differences in genetic predisposition to hypertension

Kato

2012

Hypertens Res

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Recently, large-scale meta-analyses of genome-wide association (GWA) studies have identified a number of loci significantly associated with systolic and/or diastolic blood pressure (BP). Most of the GWA studies reported to date were conducted in populations of European descent. Given the appreciable ethnic differences in clinical presentation of hypertension, studies in non-European populations allow us to assess the relevance of the findings in Europeans to other ethnic groups and to potentially discover novel variants. Before the GWA scan era, the presence of racial or ethnic differences has been widely recognized for response to antihypertensive therapies, salt sensitivity and impact of obesity on developing hypertension. Despite a limited number of genetic loci that have been proven to show substantial ethnic differences, we can assume four possible genetic mechanisms-(1) absence of target variants in other ethnic groups; (2) presence of allelic heterogeneity; (3) difference in linkage disequilibrium structure; and (4) gene-gene and gene-environment interactions. Considering such a number of potential sources of heterogeneity, we should be cautious about claiming the presence of genuine ethnic differences in genetic susceptibility to BP-related traits or hypertension. Approximately a quarter of BP-associated loci that have been reported in four meta-analyses of GWA studies (i.e., 8 out of 34 loci) appear to be common across three ethnic groups-Europeans, east Asians and south Asians. 'Transethnic' BP meta-analysis will be useful not only for revealing novel susceptibility loci and pathophysiological pathways but also for facilitating the fine mapping of common causal variants.

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Section: Salt Sensitivitymentioning

confidence: 99%

Ethnic differences in genetic predisposition to hypertension

Kato

2012

Hypertens Res

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“…Diastolic and mean BPs were similar at baseline on both salt diets establishing the saltresistant phenotype. 33,[35][36][37] Fenoldopam 34 alone decreased diastolic and mean BPs on HS diets and decreased diastolic BP on LS diets, in contrast to its ability to lower systolic and diastolic BPs in mildly and moderately hypertensive patients. 38 Fenoldopam and enalapril given together decreased diastolic and mean BPs on both salt diets (Table 2).…”

Section: Cardiovascular and Renal Hemodynamic Parameters In Response mentioning

confidence: 92%

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

Natarajan¹,

Eisner

Armando³

et al. 2016

Journal of the American Society of Nephrology

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The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D 1 -like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na + /day) and high (300 mmol Na + /day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D 1 -like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D 1 -like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions. During salt depletion, sodium balance is maintained by increased activity of several systems, including the renin-angiotensin-aldosterone (RAAS) and sympathetic nervous systems.

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“…For instance, renal dopamine production is decreased in some cases of hypertension and some human populations (African-American, Japanese) do not raise their renal production of dopamine in response to a NaCl or protein load. This may contribute to the development of salt-sensitive hypertension in these particular ethnic groups [139] . The observation that D3 -/-mice have a diminished ability to excrete an acute or chronic NaCl load, leading to the expansion of ECFV support the idea that the renal dopamine pathway regulate BP (see [140] for review).…”

Section: Prostanoid Receptorsmentioning

confidence: 99%

New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors

Morla

Edwards

Crambert

2016

WJBC

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The renal handling of Na + balance is a major determinant of the blood pressure (BP) level. The inability of the kidney to excrete the daily load of Na + represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part (i.e ., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na + excretion and are the target of many different regulatory processes that modulate Na + retention more or less efficiently. G-protein coupled receptors (GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na + absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na + excretion, this review also highlights the complexity of these different pathways, and the connections between them.

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Genetics of Salt-Sensitive Hypertension

Cited by 122 publications

References 139 publications

Ethnic differences in genetic predisposition to hypertension

Ethnic differences in genetic predisposition to hypertension

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors

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