To our knowledge, this is the first study reporting the impact of an active lifestyle on hemodynamic, HRV and oxidative stress parameters in offspring of hypertensive parents. Three important findings emerged from the present study. First, the offspring of hypertensive parents showed higher levels of DBP, cardiac sympathetic modulation and systemic reactive oxygen species. Secondly, the higher levels of the cardiac sympathetic modulation were correlated with systemic levels of hydrogen peroxide, lipoperoxidation and DBP. Finally, the major finding of this investigation lies in the fact that an active lifestyle seems to prevent early hemodynamic and HRV dysfunctions, along with oxidative stress in offspring of hypertensive parents.
Most studies on offspring of hypertensives have focused on the autonomic nervous system as a major contributor to the onset of hypertension11,12. In order to determine the direct effects of both family history and an active lifestyle on the autonomic nervous system, we selected 127 participants with or without family history of hypertension. For the assessment of the autonomic nervous system we used HRV, an effective tool to obtain reliable indices for overall sympathetic nerve activity and baroreceptor function10. Several studies have demonstrated that offspring of hypertensives had higher sympathetic activity6 as well as higher rest cardiac sympathetic modulation13. However, these autonomic dysfunctions are not necessarily accompanied by clinical symptoms, such as increased BP, as previously described13,14. Therefore, the detection of the early autonomic modulation dysfunction, before any clinical manifestation occurs, may have an important role in preventing the onset of hypertension.
In the present study, we also corroborated previously published data showing that offspring of hypertensive parents had autonomic dysfunction6,13,14, as demonstrated by higher sympathetic and lower parasympathetic modulation (LF nu and HF nu), thus reflecting in the LF/HF ratio. Pharmacological and non-pharmacological approaches have been studied for the treatment of autonomic dysfunction, prevention of end-target organ damage and the onset of hypertension15. Among non-pharmacological strategies, physical activity and/or exercise training has been found to be an effective tool in preventing hypertension26.
In our study, the active lifestyle group of offspring of hypertensives presented normalized cardiac autonomic modulation, probably associated with reduced resting HR. These results concur with previous studies involving patients with established hypertension, indicating that an active lifestyle minimizes physiological stress and autonomic alterations27,28. Taken together, our findings indicate that activity lifestyle attenuates/prevents the impact of family history on one of the most important and studied factors, i.e., sympathetic modulation, associated with hypertension development.
It should be noted that despite the unfavorable changes in HRV associated with family history of hypertension, hemodynamic values remained within the normal range. However, the sedentary offspring of hypertensive parents showed increased DBP. The physiological mechanisms underlying this increase might be explained by the increase in fat mass and cardiac sympathetic modulation observed in this group. Indeed, changes in the autonomic nervous system over the cardiovascular system tend to occur prior to the increase in BP29. We observed a positive correlation between LF/HF ratio and fat mass associated with DBP, indicating that subjects with higher fat mass and cardiac sympathetic modulation presented higher DBP. It is worth mentioning that fat mass has been associated with higher sympathetic tonus and development of hypertension30. Additionally, Hesse et al.31 have demonstrated that baroreflex sensitivity was inversely correlated with the mean BP evaluated over 24 h and positively associated with HRV. Our results corroborate with these findings, demonstrating that the S-OH group had higher levels of DBP and HRV dysfunction parameters, which occurred in an inverse manner in the physically active groups.
Oxidative stress has been found to play an important role in the development of hypertension and cardiovascular diseases9,10. Oxidative stress refers to the imbalance due to excess reactive oxygen species or oxidants over the ability of the cell to build an effective antioxidant response23. Hydrogen peroxide is an important ROS in redox signaling22. In this sense, although we did observe unchanged systemic levels of markers of oxidative damage, evaluated by lipoperoxidation and protein oxidation, higher levels of systemic hydrogen peroxide and superoxide anion were found in sedentary offspring of hypertensives, suggesting early redox imbalance associated with familial history of hypertension. It should be emphasized that previous studies have demonstrated a positive correlation between cardiac and vascular sympathetic modulation and oxidative stress in experimental model11,12. In the present study, we found a positive correlation between LF/HF ratio and hydrogen peroxide and lipoperoxidation, which suggests that increased sympathetic modulation affects oxidative stress profile.
We should like to highlight that only 7 days of fructose overload (10% in drinking water) induced impairment of autonomic control of circulation in spontaneously hypertensive rats (SHR), which is the experimental model more closely related to the essential hypertension, thus showing a strong genetic predisposition to hypertension. Moreover, autonomic changes were followed by unfavorable systemic changes in inflammatory and oxidative stress markers (15–60 days), leading to a later exacerbated increase in BP (only in 60 days) in this model2,8. In fact, several studies have associated the autonomic dysfunction on end organ damage with hypertension15,32. In this sense, one of the mechanisms thought to be involved in end organ damage is oxidative stress33. Therefore, we postulate that the early sympathetic activation in sedentary subjects with family history of hypertension may increase reactive oxygen species, leading to progressive end organ damage and increased BP. Moreover, our data support the hypothesis that an active lifestyle may blunt sympathetic overactivity, body fat accumulation and reactive oxygen species production in offspring of hypertensives, preventing organ damage and BP changes.
Some limitations of the present study need to be addressed to. The first one lies in the use of questionnaires alone to assess the role of family history in hypertension; more extensive information regarding the BP values of parents (normotensive or hypertensive) would be desirable34. Secondly, gender limitation may be an issue, since only men have been tested in this trial. Previous studies have shown that women during reproductive life had higher HF band and lower LF band than men35, and sedentary lifestyle induces impairment in cardiac autonomic modulation in women36. Thus, further studies are needed to determine to what extent gender affects HRV in the offspring of hypertensives. Thirdly, we used an auscultation method for assessing the BP, which is a rather limited procedure when compared to other more comprehensive methods. However, all safeguards have been met ensure the reliability of the final results recorded.
In conclusion, our results lend strong support to the presence of early autonomic dysfunction in offspring of hypertensive parents, which was associated with a systemic increase in reactive oxygen species and blood pressure. However, our most important finding lies in the attenuation of such disorders in physically active offspring of hypertensives, emphasizing the importance of a physically active lifestyle in preventing early dysfunctions potentially associated with the onset of hypertension.