title: eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.
abstract: Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function.
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Department of Physiology, Section of Exercise Physiology, Federal University of São Paulo, São Paulo, Brazil. Electronic address: silva.bruno@unifesp.br.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Silva
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Thales C
authors.initials: TC
authors.lastname: Barbosa
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Fabricia J
authors.initials: FJ
authors.lastname: Neves
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Allan K
authors.initials: AK
authors.lastname: Sales
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Natalia G
authors.initials: NG
authors.lastname: Rocha
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Renata F
authors.initials: RF
authors.lastname: Medeiros
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Felipe S
authors.initials: FS
authors.lastname: Pereira
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Vinicius P
authors.initials: VP
authors.lastname: Garcia
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Fabiane T
authors.initials: FT
authors.lastname: Cardoso
authors.affiliation: Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Antonio C L
authors.initials: AC
authors.lastname: Nobrega
mesh_terms: D000328:Adult; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005542:Forearm / Q000502:physiology; D060005:Genotyping Techniques; D006239:Haplotypes; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Autonomic nervous system; Exercise; Genetic variation; Nitric oxide