eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise

• Published in: Autonomic neuroscience Vol. 186; pp. 77 - 84
• Main Authors: Silva, Bruno M, Barbosa, Thales C, Neves, Fabricia J, Sales, Allan K, Rocha, Natalia G, Medeiros, Renata F, Pereira, Felipe S, Garcia, Vinicius P, Cardoso, Fabiane T, Nobrega, Antonio C.L
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2014
• Subjects: Adult; Advanced Basic Science; Autonomic nervous system; Baroreflex - physiology; Blood Pressure - physiology; Exercise; Exercise - physiology; Exercise Test; Female; Forearm - physiology; Genetic variation; Genotyping Techniques; Haplotypes; Heart Rate - physiology; Humans; Ischemia - physiopathology; Male; Medical Education; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Polymorphism, Genetic; eNOS; low density lipoprotein; Genetic variation; HRR; HR; systolic blood pressure; low frequency; ANCOVA; DBP; Exercise; diastolic blood pressure; Autonomic nervous system; peak oxygen consumption; heart rate recovery; endothelial nitric oxide synthase; heart rate at the first minute of recovery; HRRτ; RFLP; nitric oxide; body mass index; root mean square of successive beat interval differences; index of spontaneous baroreflex sensitivity; SEM; Alpha-LF; high density lipoprotein; standard error of the mean; analysis of covariance; time to obtain 63% of the total heart rate decay response; PCR; NO; HRR 1min; V .O 2peak; HDL; restriction fragment length polymorphism; analysis of variance; deoxyribonucleic acid; ANOVA; LDL; polymerase chain reaction; BMI; SBP; heart rate; high frequency; ratio between low and high frequency; H1; haplotype 2; haplotype 1; H2; RMSSD; DNA; LF; LF/HF; HF; HRR1min; Nitric oxide; V.O2peak
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2014.09.001

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.