Α2b-adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women

ABSTRACT OBJECTIVE: To investigate the association of short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the _α_2B-adrenergic receptor (_α_2B-AR) gene polymorphism with the

cardiac autonomic responsiveness during sustained isometric handgrip exercise. DESIGN: Cross-sectional clinical study. SUBJECTS: In all, 97 normotensive obese women (body mass index

(BMI)=33.2 kg/m2). Of these, 78 (80.41%) were genotyped as Glu12/Glu12, 13 (13.40%) as Glu12/Glu9 and six (6.19%) as Glu9/Glu9 form. MEASUREMENTS: The sympathovagal balance was assessed by

means of power spectral analysis of heart rate variability at rest and during sustained isometric handgrip exercise at 30% of maximal voluntary handgrip contraction for 3 min. Two spectral

components were analysed: low-frequency component reflecting sympathetic efferent activity and high-frequency power (HFnu) reflecting parasympathetic modulation. In addition, a normalized

low-frequency power (LFnu) and HFnu were analysed. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: There were no differences in

baseline measurements among groups. The absolute level of LFnu throughout handgrip exercise was significantly lower in Glu9/Glu9 subjects compared with other genotypes, while the decline of

absolute HFnu was significantly smaller compared with Glu12/Glu12 genotype. CONCLUSION: These findings suggest that 12Glu9 deletion polymorphism of the _α_2B-AR gene (Glu9/Glu9 genotype)

might result in reduced autonomic responsiveness by altering cardiac sympathetic and vagal function during sustained handgrip exercise in normotensive obese women. Access through your

institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print

issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to

local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT

BEING VIEWED BY OTHERS REDUCED HEART-RATE VARIABILITY AND INCREASED RISK OF HYPERTENSION—A PROSPECTIVE STUDY OF THE ELSA-BRASIL Article 18 January 2021 EPIGALLOCATECHIN GALLATE ENHANCES

SYMPATHETIC HEART RATE VARIABILITY AND DECREASES BLOOD PRESSURE IN OBESE SUBJECTS: A RANDOMIZED CONTROL TRIAL Article Open access 16 September 2024 EFFECTS OF AEROBIC, RESISTANCE AND

CONCURRENT EXERCISE ON PULSE WAVE REFLECTION AND AUTONOMIC MODULATION IN MEN WITH ELEVATED BLOOD PRESSURE Article Open access 12 January 2021 REFERENCES * Heinonen P, Koulu M, Pesonen U,

Karvonen MK, Rissanen A, Laakso M et al. Identification of a three-amino acid deletion in the _α_2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese

subjects. _J Clin Endocr Metab_ 1999; 84: 2429–2433. CAS  Google Scholar  * Baldwin CT, Schwartz F, Baima J, Burzstyn M, DeStefano AL, Gavras I et al. Identification of a polymorphic

glutamic acid streach in the _α_2B-adrenergic receptor and lack of linkage with essential hypertension. _Am J Hypertens_ 1999; 12: 853–857. Article  CAS  Google Scholar  * Sivenius K,

Niskanen L, Laakso M, Uusitupa M . Effects of a three-amino acid deletion in the _α_2B-adrenergic receptor gene on long-term body weight change in Finish non-diabetic and type 2 diabetic

subjects. _Int J Obes Relat Metab Disord_ 2001; 25: 1609–1614. Article  CAS  Google Scholar  * Sykiotis GP, Polyzogopoulou E, Georgopoulos NA, Trakada G, Spyropoulos K, Kalfarentzos F et al.

The _α_2B-adrenergic receptor deletion/insertion polymorphism in morbid obesity. _Clin Auton Res_ 2003; 13: 203–207. PubMed  Google Scholar  * Small KM, Brown KM, Forbes SL, Liggett SB .

Polymorphic deletion of the three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization.

_J Biol Chem_ 2001; 276: 4917–4922. Article  CAS  Google Scholar  * Sivenius K, Niskanen L, Laakso M, Uusitupa M . A deletion in the _α_2B-adrenergic receptor gene and autonomic nervous

function in central obesity. _Obes Res_ 2003; 11: 962–970. Article  CAS  Google Scholar  * Pagani M, Lombardi F, Guzzetti S . Power spectral analysis of heart rate and arterial pressure

variability as a marker of sympatho-vagal interaction in man and conscious dog. _Circ Res_ 1986; 59: 178–193. Article  CAS  Google Scholar  * Akselrod S, Gordon D, Madwed JB, Snidman NC,

Shannon DC, Cohen RJ . Hemodynamic regulation: investigation by spectral analysis. _Am J Phys_ 1985; 249: H867–H875. CAS  Google Scholar  * Montano N, Ruscone TG, Porta A, Lombardi F, Pagani

M, Malliani A . Power spectrum analysis of heart rate variability to assess autonomic changes in sympatho-vagal balance during graded orthostatic tilt. _Circulation_ 1994; 90: 1826–1831.

Article  CAS  Google Scholar  * Piccirillo G, Vetta F, Fimognari FL, Ronzoni S, Lama J, Cacciafesta M et al. Power spectral analysis of heart rate variability in obese subjects: evidence of

decreased cardiac sympathetic responsiveness. _Int J Obes Relat Metab Disord_ 1996; 20: 825–829. CAS  PubMed  Google Scholar  * Paolisso G, Manzella D, Ferrara N, Gambardella A, Abete P,

Tagliamonte MR et al. Glucose ingestion affects cardiac ANS in healthy subjects with different amounts of body fat. _Am J Phys_ 1997; 273: E471–E478. CAS  Google Scholar  * Matsumoto T,

Miyawaki C, Ue H, Kanda T, Zenji C, Moritani T . Autonomic responsiveness to acute cold exposure in obese and non-obese young women. _Int J Obes Relat Metab Disord_ 1999; 23: 793–800.

Article  CAS  Google Scholar  * Moritani T, Matsumoto T, Miawaki T, Ue H, Zenji C . Effects of capsaicin on sympathetic nervous system activity and diet-induced thermogenesis in lean and

obese young women. _Proceedings of the Fourth Annual Congress of the European College of Sports Science_. Rome, 1999, pp 47. Google Scholar  * Matsumoto T, Miyawaki C, Ue H, Kanda T,

Yoshitake Y, Moritani T . Comparison of thermogenic sympathetic response to food intake between obese and non-obese young women. _Obes Res_ 2001; 9: 78–85. Article  CAS  Google Scholar  *

Jung RT, Shetty PS, James WP, Barrand MA, Callingham BA . Plasma catecholamines and autonomic responsiveness in obesity. _Int J Obes Res Metab Disord_ 1982; 6: 131–141. CAS  Google Scholar 

* Gustafson AB, Kalkhoff RK . Influence of sex and obesity on plasma catecholamine response to isometric exercise. _J Clin Endocr Metab_ 1982; 55: 703–708. Article  CAS  Google Scholar  *

Joint National Committe on Detection, Evaluation, and Treatment of High Blood Pressure. The Sixth Report of Joint Committee on Detection, Evaluation, and Treatment of High Blood Pressure

(JNC VI). _Arch Intern Med_ 1997; 157: 2413–2445. * Trombetta IC, Batalha LT, Rondon MU, Laterza MC, Kuniyoshi FH, Gowdak MM et al. Weight loss improves neurovascular and muscle metaboreflex

control in obesity. _Am J Physiol Heart Circ Physiol_ 2003; 285: H974–H982. Article  CAS  Google Scholar  * Trombetta IC, Batalha LT, Rondon MU, Laterza MC, Frazzatto E, Alves MJ et al.

Gly16+Glu27 beta2-adrenoceptor polymorphisms cause increased forearm blood flow responses to mental stress and handgrip in humans. _J Appl Physiol_ 2005; 98: 787–794. Article  CAS  Google

Scholar  * Boot AM, Bouquet J, Ridder MA, Krenning EP, de Muinck Keizer-Schrama SM . Determinants of body composition measured by dual-energy X-ray absorptiometry in Dutch children and

adolescent. _Am J Clin Nutr_ 1997; 66: 232–238. Article  CAS  Google Scholar  * Matthews DR, Hosker JP, Rudensky AS, Naylor BA, Treacher DF, Turner RC . Homeostasis Model Assessment: insulin

resistance and beta-cell function from fasting plasma glucose and insulin concentration in man. _Diabetologia_ 1985; 28: 412–419. Article  CAS  Google Scholar  * Tai MM . A mathematical

model for the determination of total area under glucose tolerance and other metabolic curves. _Diabetes Care_ 1994; 17: 152–154. Article  CAS  Google Scholar  * Suzuki N, Matsunaga T,

Nagasumi K, Yamamura T, Shihara N, Moritani T et al. Alpha2B-adrenergic receptor deletion polymorphism associates with. _J Clin Endocr Metab_ 2003; 88: 1184–1187. Article  CAS  Google

Scholar  * Zaza A, Lombardi F . Autonomic indexes based on the analysis of heart rate variability: a view from the sinus node. _Cardiovasc Res_ 2001; 50: 434–442. Article  CAS  Google

Scholar  * Lind AR, McNicol GW . Muscular factors which determine the cardiovascular responses to sustained and rhythmic exercise. _Can Med Assoc J_ 1967; 96: 706–715. CAS  PubMed  PubMed

Central  Google Scholar  * Limbird LE . Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms. _FASEB J_ 1988; 2: 2686–2695 (review). Article  CAS  Google

Scholar  * Tavares A, Handy DE, Bogdanova NN, Rosene DL, Gavras H . Localization of alpha 2A and alpha 2B-adrenergic receptors subtypes in brain. _Hypertension_ 1996; 27: 449–455. Article 

CAS  Google Scholar  * Ruffolo Jr RR, Nichols AJ, Stadel JM, Hieble JP . Pharmacologic and therapeutic applications of _α_2B-adrenoreceptor subtypes. _Annu Rev Pharmacol Toxicol_ 1993; 67:

243–279. Article  Google Scholar  * Lucini D, Mela GS, Malliani A, Pagani M . Impairment in cardiac autonomic regulation preceding arterial hypertension in humans. Insights from spectral

analysis of beat-by-beat cardiovascular variability. _Circulation_ 20002; 106: 2673–2679. Article  Google Scholar  * Nagai N, Sakane N, Ueno LM, Hamada T, Moritani T . The 3826 → G variant

of the uncoupling protein 1 gene diminishes postprandial thermogenesis after high fat meal in healthy boys. _J Clin Endocr Metab_ 2003; 88: 5661–5667. Article  CAS  Google Scholar  * Brown

TE, Beightol LA, Koh J, Eckberg DL . Important influence of respiration on human R–R interval power spectra is largely ignored. _J Appl Phys_ 1993; 75: 2310–2317. CAS  Google Scholar  *

Hirsch JÁ, Bishop B . Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate. _Am J Phys_ 1981; 241: H620–H629. CAS  Google Scholar  * Borst C, Wieling W, van

Brederode JF, Hond A, de Rijk LG, Dunning AJ . Mechanisms of initial heart rate response to postural change. _Am J Phys_ 1982; 243: H676–H681. CAS  Google Scholar  * Hollander AP, Bouman LN

. Cardiac acceleration in man by a muscle–heart reflex. _J Appl Phys_ 1975; 38: 272–278. CAS  Google Scholar  * Martin CE, Shaver JA, Leon DF, Thompson ME, Reddy OS, Leonard JJ . Autonomic

mechanisms in hemodynamic responses to isometric exercise. _J Clin Invest_ 1974; 54: 104–115. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This study was supported by

Fundação de Amparo à Pesquisa do Estado de São Paulo Grant 1998/15983-8 and, in part, by Fundação Zerbini. Dra Linda Massako Ueno has been supported by Fundação de Amparo a Pesquisa do

Estado de São Paulo (FAPESP#03/10881-2) and Maria do Socorro Brasileiro by Universidade Federal de Pernambuco. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Heart Institute (InCor), Medical

School, University of São Paulo, São Paulo, Brazil L M Ueno, I C Trombetta, M do Socorro Brasileiro, C Irigoyen & C E Negrão * Department of Endocrinology, Clinical Hospital, University

of São Paulo, Medical School, São Paulo, Brazil E S T Frazzatto, L T Batalha & S M F Villares * School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil P C

Brum & C E Negrão Authors * L M Ueno View author publications You can also search for this author inPubMed Google Scholar * E S T Frazzatto View author publications You can also search

for this author inPubMed Google Scholar * L T Batalha View author publications You can also search for this author inPubMed Google Scholar * I C Trombetta View author publications You can

also search for this author inPubMed Google Scholar * M do Socorro Brasileiro View author publications You can also search for this author inPubMed Google Scholar * C Irigoyen View author

publications You can also search for this author inPubMed Google Scholar * P C Brum View author publications You can also search for this author inPubMed Google Scholar * S M F Villares View

author publications You can also search for this author inPubMed Google Scholar * C E Negrão View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to C E Negrão. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ueno, L., Frazzatto, E., Batalha, L. _et al._

_α_2B-Adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women. _Int J Obes_ 30, 214–220 (2006).

https://doi.org/10.1038/sj.ijo.0803140 Download citation * Received: 30 November 2004 * Revised: 30 August 2005 * Accepted: 09 September 2005 * Published: 25 October 2005 * Issue Date: 01

February 2006 * DOI: https://doi.org/10.1038/sj.ijo.0803140 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * _α_2B-adrenergic receptor

polymorphism * cardiac autonomic responsiveness