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Endothelial Nitric Oxide Synthase Polymorphisms and Adaptation of Parasympathetic Modulation to Exercise Training

SILVA, BRUNO M.1,2,3; NEVES, FABRICIA J.1,2; NEGRÃO, MARCELO V.4; ALVES, CLEBER R.4; DIAS, RODRIGO G.4; ALVES, GUILHERME B.4; PEREIRA, ALEXANDRE C.4; RONDON, MARIA U.4; KRIEGER, JOSÉ E.4; NEGRÃO, CARLOS E.4,5; DA NÓBREGA, ANTONIO CLAUDIO LUCAS1,2,3

Medicine & Science in Sports & Exercise: September 2011 - Volume 43 - Issue 9 - pp 1611-1618
doi: 10.1249/MSS.0b013e3182152197
Basic Sciences

Purpose: There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (−786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training.

Methods: Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (V˙O2peak) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day−1, during 18 wk).

Results: Training increased V˙O2peak (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the −786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (−786TT) = 2% ± 89% vs polymorphic (−786TC/CC) = −28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = −18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (−786T/4b/894G) and polymorphic alleles at positions −786 and 894 (−786C/4b/894T) (−6% ± 56% vs −41% ± 50%, median ± quartile range, P = 0.04).

Conclusions: The polymorphic allele at position −786 and the haplotype containing polymorphic alleles at positions −786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.

1Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, BRAZIL; 2Graduate Program in Cardiovascular Sciences, Fluminense Federal University, Niterói, BRAZIL; 3Graduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, BRAZIL; 4Heart Institute (InCor), University of São Paulo Medical School, São Paulo, BRAZIL; and 5School of Physical Education and Sport, University of São Paulo, São Paulo, BRAZIL

Address for correspondence: Antonio Claudio Lucas da Nóbrega, M.D., Rua Professor Hernani Pires de Melo 101, sala 106, São Domingos, Niterói, Riode Janeiro 24210-130, Brasil; E-mail: anobrega@id.uff.br.

Submitted for publication October 2010.

Accepted for publication February 2011.

©2011The American College of Sports Medicine