Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene

Abstract

Rondon MU. Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene. Physiol Genomics 42A: 71-77, 2010. First published July 6, 2010; doi:10.1152/physiolgenomics.00145.2009.-Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n ϭ 37; age 27 Ϯ 1 yr) and CTϩCC (n ϭ 35; age 26 Ϯ 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P ϭ 0.17) and mean blood pressure (P ϭ 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CTϩCC individuals (0.39 Ϯ 0.12 vs. 1.08 Ϯ 0.27 units, P ϭ 0.01). Exercise training significantly increased peak VO 2 in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P ϭ 0.03), but not in CTϩCC individuals (P ϭ 0.49), leading to an equivalent FVC response between TT and CTϩCC individuals (1.05 Ϯ 0.18 vs. 1.59 Ϯ 0.27 units, P ϭ 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training. genetics NITRIC OXIDE (NO) is synthesized in the endothelium by the endothelial isoform of nitric oxide synthase (eNOS) (27), a protein encoded in the long arm of chromosome 7 (19). NO is responsible for the maintenance of vascular tone due to its capability of inducing vasodilatation in response to shear stress (9, 26). A disruption of eNOS function or of its production can decrease NO bioavailability and, consequently, lead to deleterious effects on endothelial and vasomotor function. Recent findings suggest that, apart from classic risk factors such as smoking and diabetes, genetic variants are capable of altering eNOS expression and enzymatic activity (21,23,36).Among the genetic variants present in the eNOS gene, considerable attention has been focused on the T786C polymorphism, which is located on the 5=-flanking region of the promoter region of the eNOS gene. The C allele of this polymorphism has been associated with coronary spasm (23) and blunted vasodilato...

The presence of the NOS3 gene polymorphism for intron 4 mitigates the beneficial effects of exercise training on ambulatory blood pressure monitoring in adults

“…Overall, these studies have shown that the presence of a polymorphism for the NOS3 gene attenuates the beneficial effect of exercise training measured by flow-mediated dilatation (19,43), BP (46,53,54), and NO production (54). In contrast, some studies have shown that exercise training overcomes the unfavorable effect of NOS3 gene polymorphisms on cardiometabolic responses (64,65), whereas others have shown that volunteers with NOS3 gene polymorphisms are equally responsive in lowering BP to exercise training compared with subjects without NOS3 gene polymorphisms (20,49).…”

Alpha2A-adrenergic receptor and eNOS genetic polymorphisms are associated with exercise muscle vasodilatation in apparently healthy individuals

“…Carriers of CC genotype showed greater increase in forearm vascular conductance during exercise than carriers of allele T. In a study with 72 healthy and physically active individuals, carriers of eNOS 786TT genotype showed impaired exercise forearm vasodilatation than carriers of eNOS 786TC and 786CC genotypes, which allowed the hypothesis that T allele may increase susceptibility for endothelial dysfunction [12]. Interestingly, in this study, carriers of eNOS 786TT genotype, despite worse baseline exercise vasodilatation, had better improvement in muscle vasodilatation after 18 week-exercise training than carriers of eNOS 786C allele.…”

“…Studies with small samples, ranging from 33 to 72 participants, have suggested that muscle vasodilatation during exercise may be modulated by functional polymorphisms in genes of physiologic pathways linked to cardiovascular regulation such as beta-adrenergic receptors, bradykinin B 2 receptor (BDKRB 2) and endothelial nitric oxide synthase (eNOS) [10], [11], [12], [13]. Additionally, experimental studies with healthy individuals have demonstrated that alpha-adrenergic receptors mediate an important role on the modulation of the vascular tonus at rest [14] and during exercise [15].…”

Genetic Regulation of Endothelial Vasomotor Function

“…Patients carrying C allele at T −786 → C had a smaller improvement in APV (~36%) than patients carrying T allele (~ 81%), whereas a polymorphic effect of G 894 → T was not observed. Similarly, 18 weeks of exercise training increased forearm vascular conductance during handgrip exercise in TT carriers, but not in CT or CC carriers at T −786 → C of NOS3 (Negrao et al, 2010). For other vascular-related genes, there is limited information regarding their role in improved endothelial function with exercise training (Park et al, 2007; Alves et al, 2013; Lemos et al, 2016).…”