Association between endothelial nitric oxide synthase and the renin-angiotensin-aldosterone system polymorphisms, blood pressure and training status in normotensive/pre-hypertension and hypertensive older adults: a pilot study

ABSTRACT

Introduction:Variations in blood pressure (BP) are, in part, genetically determined and some polymorphisms of renin-angiotensin- aldosterone system (RAAS) and synthase of endothelial nitric oxide (eNOS) have been related to hypertension (HT). Conversely, physical exercise is considered a non-pharmacological tool for HT control, treatment, and prevention.

Objective: The purpose of this study is to investigate the relationship between eNOS and RAAS polymorphisms, their epistatic interaction, and the respective humoral factors in the BP control in normotensive/pre-hypertension and hypertensive older adults and how this relationship can be modulated by training status (TS) level.

Methods:A total of 155 older adults (66.94 ± 6.83 years old) performed the following evaluations: AAHPERD battery test to determine the general functional fitness index (GFFI), systolic and diastolic blood pressure (SBP and DBP), blood collection for DNA extraction, analysis of eNOS gene polymorphisms rs2070744; rs61722009 and rs1799983 and RAAS polymorphisms rs699; rs1799752 and rs5186, and quantification of ACE activity (Fluorimetric Assay) and nitrite concentration (Chemiluminescence Method).

Results and Conclusion:Good TS level appears to exert greater influence on SBP for G2 and G3 (G1: 125.79 ± 14.03/ G2: 119.91 ± 11.72^/G3: 119.71 ± 10.85) and on NO₂ for G3 (G1: 0.42 ± 0.25/ G2: 0.54 ± 0.45/ G3: 0.71 ± 0.52). No associations were observed between eNOS and RAAS polymorphisms, but the epistasis was identified between eNOS polymorphism, rs2070744, and RAAS polymorphism, rs699, revealing a statistically significant interaction (p = .0235) with training score of 0.63, a training test accuracy of 0.61 and a cross-validation consistency of 10/10. This result suggests an increased risk of hypertension.

KEYWORDS:

• Aging
• exercise
• genetics
• heredity
• hypertension

Disclosure Statement

The authors report no conflict of interest.

Data availability statement

All data generated or analyzed during this study are included in this manuscript, in the results section and supplementary material. The corresponding author is available to answer any questions. Contact by e-mails: [email protected] and [email protected]

Study limitations

The design of this study (cross-sectional) does not allow the establishment of cause and effect relationship, only association between results. There was no stratification by sex or age, only by normotensive/pre-hypertension or hypertensive. There was not dietary control which could affect some variables. Training status levels were only evaluated in a general way regardless of the type of exercise performed.

Statement of guidelines and regulation

“All methods were carried out in accordance with guidelines and regulations”.

All procedures were previously approved by Institutional Review Board of UNESP - São Paulo State University (CEP/FC-UNESP no.323.427).

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website

Additional information

Funding

This study was supported by the Higher Education Personnel Improvement Coordination - Brazil (CAPES) – [Finance Code 001] and for São Paulo Research Foundation (FAPESP): [Grants no 2015/24847-8 to ASZ and 2015/03965-2 to CFS].