Why is plasma renin activity lower in populations of African origin?

Sagnella, Giuseppe A.

doi:10.1038/sj.jhh.1001127

Cited by 89 publications

(65 citation statements)

References 70 publications

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“…Our recent data indicate that impaired SIPN is approximately twice as prevalent in black as in white youth (40% versus 20%) (Harshfield et al, Annual Meeting of Society of Behavioral Medicine, April 13-16, 2005, Boston). The genetic and environmental determinants of salt sensitivity and pressure natriuresis are speculated to be race-related (25).…”

Section: Grk4 Gene and Sodium Excretionmentioning

confidence: 99%

The G Protein-Coupled Receptor Kinase 4 Gene Modulates Stress-Induced Sodium Excretion in Black Normotensive Adolescents

Zhu

Wang

et al. 2006

Pediatr Res

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Approximately 20 -40% of adolescents have shown a reduction of urinary sodium excretion (U Na V) in response to blood pressure (BP) increase during behavioral stress. G protein-coupled receptor kinase 4 (GRK4) mediates the pressure and natriuresis relation. The present study investigated the impact of GRK4 genetic variants on U Na V under stress. A total of 664 normotensive adolescents including whites and blacks (17.6 Ϯ 3.3 yrs, 43.4% blacks) were recruited. Participants were subjected to a stress-protocol including three 10-min tasks (a social competence interview, a virtual reality car driving simulation test, and a video game challenge), concluded by a urine collection. Three functional polymorphisms including R65L, A142V and A486V were genotyped. Given blacks compared with whites had significantly higher systolic BP (SBP) levels during rest (p Ͻ 0.001) and stress (p Յ 0.001), there was no statistical difference in U Na V in response to stress between the two ethnic groups. In blacks, compared with R65R homozygotes, individuals with R65L or L65L genotype had significantly lower levels of stress-induced U Na V (8.42 Ϯ 0.63 versus 9.85 Ϯ 0.37 mEq/h, p ϭ 0.01). In summary, BP elevation seems uncoupled with U Na V increase during behavioral stress in black adolescents. The 65L allele of the GRK4 gene is associated with stress-induced U Na V reduction, suggesting impaired sodium handling in affected black youth. E ssential hypertension is determined by gene and environment interactions, and has its origin in childhood. Blood pressure (BP) increase during a sustained period of behavioral stress is typically accompanied by a compensatory increase in urinary sodium excretion (U Na V) (1,2). Our previous data show that an inadequate compensatory increase in U Na V in response to stress occurs in 20 -40% of adolescents aged 15-19 y (Harshfield et al. Annual Meeting of Society of Behavioral Medicine, April 13-16, 2005, Boston), which may predict the development of hypertension (1,2). In particular, we have recently demonstrated that U Na V in response to stress is a heritable phenotype in a multi-ethnic cohort of adolescents (Ge et al., Annual meeting of the American Society of Human Genetics, October 25-29, 2005, Salt Lake City). However, no candidate gene association study has been performed to date. Dopamine enhances renal sodium excretion, diuresis and natriuresis via dopamine receptors D (DRD) in the renal proximal tubules (3-5). G protein-coupled receptor kinase 4 (GRK4) regulates DRD1 phosphorylation, desensitization and internalization (6,7). Although functional single nucleotide polymorphisms (SNPs) of the GRK4 gene have been associated with hypertension in adult populations (8 -11), the impact of these variants on sodium homeostasis in humans remains unknown. Thus we conducted association analyses of the GRK4 polymorphisms in relation to stress-induced U Na V in a sample of young normotensive white and black twins. METHODS Study population.A total of 664 normotensive twin subjects including whites a...

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Section: Grk4 Gene and Sodium Excretionmentioning

confidence: 99%

The G Protein-Coupled Receptor Kinase 4 Gene Modulates Stress-Induced Sodium Excretion in Black Normotensive Adolescents

Zhu

Wang

et al. 2006

Pediatr Res

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“…In our total HyperPATH cohort study, we confirmed that ALDO, PRA, and potassium levels on a LIB salt diet were lower in AD than ED, as has been shown by others (1)(2)(3)(4)(5)(6)24). Because of limited genotyping data, we also performed analyses in a 2:1 restricted subcohort.…”

Section: Discussionmentioning

confidence: 55%

“…Compared with persons of European descent (ED), individuals of African descent (AD) are known to: (i) be more susceptible to cardiovascular disease (CVD); (ii) have a greater frequency of hypertension (HTN) (particularly salt-sensitive HTN); (iii) have more cardiovascular (CV) damage with HTN; (iv) have lower plasma renin activity (PRA); and (v) more resistant HTN (1)(2)(3)(4)(5)(6). Of interest, these same characteristics also are associated with increased aldosterone (ALDO) production, e.g., primary aldosteronism.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated aldosterone secretion in persons of African descent with endothelin-1 gene variants

et al. 2017

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“…Black patients have low renin activity [5] coupled with lower aldosterone [6]. On the other hand, there is an excessive RAAS system-dependent target organ damage in black hypertensive patients.…”

Section: Hypertension In Patients With African Ancestrymentioning

confidence: 99%