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Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone.

ABSTRACT: BACKGROUND:Black women have one of the highest prevalence rates of hypertension and obesity in the United States. We previously reported that sympathetic activation induced by obesity is a significant contributor to hypertension in white patients. It is unknown whether sympathetic activity similarly contributes to hypertension in obese black women. METHODS AND RESULTS:We studied 42 obese women (16 white, body mass index 36±4 kg/m2, 44% with hypertension; 26 black, body mass index 35±4 kg/m2, 46% with hypertension). Antihypertensive medications were discontinued for 2 weeks before the day of the study. All patients underwent complete autonomic blockade with trimethaphan at a dosage of 4 mg/min. Resting sympathetic activity determined from muscle sympathetic nerve recordings was similar between obese black women with hypertension and those with normotension. In whites, sympathetic activity was elevated in obese patients with hypertension compared with normotension; the decrease in mean arterial blood pressure produced by trimethaphan was greater in obese white patients with hypertension compared with those with normotension (-26.8±9.7 mm Hg versus -14.8±7.9 mm Hg, P=0.02). In contrast, there was no difference in the depressor responses induced by trimethaphan between obese black women with hypertension and those with normotension (-15.5±10.5 mm Hg versus -12.3±10.2 mm Hg, P=0.45). Mean arterial blood pressure remained elevated in obese blacks with hypertension compared with those with normotension during trimethaphan infusion (83.7±15.0 mm Hg versus 71.7±9.8 mm Hg, P=0.02). Heart rate increased similarly with trimethaphan between white (P=0.11) and black (P=0.76) women with hypertension and normotension. CONCLUSIONS:These findings suggest that sympathetic activity does not contribute to hypertension in obese black women and provide further evidence for racial differences in hypertension mechanisms.

SUBMITTER: Marinos A

PROVIDER: S-EPMC5721777 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone.

Marinos Alejandro A Gamboa Alfredo A Celedonio Jorge E JE Preheim Brock A BA Okamoto Luis E LE Ramirez Claudia E CE Arnold Amy C AC Diedrich Andre A Biaggioni Italo I Shibao Cyndya A CA

Journal of the American Heart Association 20171118 11

<h4>Background</h4>Black women have one of the highest prevalence rates of hypertension and obesity in the United States. We previously reported that sympathetic activation induced by obesity is a significant contributor to hypertension in white patients. It is unknown whether sympathetic activity similarly contributes to hypertension in obese black women.<h4>Methods and results</h4>We studied 42 obese women (16 white, body mass index 36±4 kg/m<sup>2</sup>, 44% with hypertension; 26 black, body ...[more]

PMID: 29151035

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Project description:BackgroundAlthough it has long been recognized that smooth muscle Na/K ATPase modulates vascular tone and blood pressure (BP), the role of its accessory protein phospholemman has not been characterized. The aim of this study was to test the hypothesis that phospholemman phosphorylation regulates vascular tone in vitro and that this mechanism plays an important role in modulation of vascular function and BP in experimental models in vivo and in humans.MethodsIn mouse studies, phospholemman knock-in mice (PLM3SA; phospholemman [FXYD1] in which the 3 phosphorylation sites on serines 63, 68, and 69 are mutated to alanines), in which phospholemman is rendered unphosphorylatable, were used to assess the role of phospholemman phosphorylation in vitro in aortic and mesenteric vessels using wire myography and membrane potential measurements. In vivo BP and regional blood flow were assessed using Doppler flow and telemetry in young (14-16 weeks) and old (57-60 weeks) wild-type and transgenic mice. In human studies, we searched human genomic databases for mutations in phospholemman in the region of the phosphorylation sites and performed analyses within 2 human data cohorts (UK Biobank and GoDARTS [Genetics of Diabetes Audit and Research in Tayside]) to assess the impact of an identified single nucleotide polymorphism on BP. This single nucleotide polymorphism was expressed in human embryonic kidney cells, and its effect on phospholemman phosphorylation was determined using Western blotting.ResultsPhospholemman phosphorylation at Ser63 and Ser68 limited vascular constriction in response to phenylephrine. This effect was blocked by ouabain. Prevention of phospholemman phosphorylation in the PLM3SA mouse profoundly enhanced vascular responses to phenylephrine both in vitro and in vivo. In aging wild-type mice, phospholemman was hypophosphorylated, and this correlated with the development of aging-induced essential hypertension. In humans, we identified a nonsynonymous coding variant, single nucleotide polymorphism rs61753924, which causes the substitution R70C in phospholemman. In human embryonic kidney cells, the R70C mutation prevented phospholemman phosphorylation at Ser68. This variant's rare allele is significantly associated with increased BP in middle-aged men.ConclusionsThese studies demonstrate the importance of phospholemman phosphorylation in the regulation of vascular tone and BP and suggest a novel mechanism, and therapeutic target, for aging-induced essential hypertension in humans.

Dataset Information

Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone.

Publications

Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone.

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