Cardiovascular autonomic control has been widely studied in different pathophysiological conditions, and these studies have guided diagnoses, treatments and used as predictors of cardiovascular morbidity and mortality [19, 22]. For SAH, an increase in sympathetic participation and/or reduction of vagal participation in the cardiac autonomic balance is frequently observed in several parameters evaluated [4, 5]. In most cases, these changes result in a reduction in BRS [4, 23]. In turn, when indices that quantify cardiac autonomic modulation are used, it is common to observe a decrease in HRV, and together with a reduction in BRS, they indicate an important loss in autonomic mechanisms of cardiovascular protection.
On the other hand, normotensive adult men and women, although sharing the same autonomic mechanisms of cardiovascular autonomic regulation, they show a significant difference in cardiac autonomic modulation regulation. In this case, women have a vagal predominance of cardiac autonomic modulation, while men have a predominance of sympathetic modulation [10, 11]. However, little is known about these differences in pathophysiological conditions, such as cardiovascular diseases. Thus, it is common for studies to include men and women, without considering these particularities of cardiac autonomic control due to sex. In this case, our results showed that women and men with SAH have differences in cardiac autonomic regulation, specifically, a predominance of vagal autonomic modulation was seen for women and sympathetic autonomic modulation for men. However, the absolute HRV values found in the present study are much lower when compared to the normotensive groups, mainly for the HF oscillations in the men group. In this case, the results corroborate the statement that SAH leads to the HRV reduction, an important autonomic change. Interestingly, the reduction HRV did not affect the balance of autonomic modulation, therefore, the predominance was similar to that observed in normotensive women and men. The reason for maintaining the vagal component predominance in the cardiac autonomic balance in hypertensive women is uncertain, however, the sexual characteristics, mainly the sexual female hormones, might be playing a role in this. Estrogens might be the main hormones at play, since experimental and clinical studies have shown that they play an important role in autonomic regulation, increasing vagal autonomic modulation and reducing cardiac sympathetic autonomic modulation [7]. Furthermore, other studies indicate that estrogens might influence the vascular tone regulation and, consequently, arterial blood pressure by different mechanisms such as the release of vasodilating factors from the endothelium, antioxidant and anti-inflammatory factors [6, 24, 25], down regulation of angiotensin-converting enzyme [26], reduced activity of angiotensin II (AT1) receptors [27], which together would cause a positive influence on cardiac contractility [9]. Corroborating this information, our results showed that women had lower BP values, even if they underwent identical pharmacological treatment (losartan).
Studies in the literature have shown that male hormones also have influence on the cardiovascular autonomic control [28]. In men, the excess of androgens seems to cause vagal cardiac dysfunction, in addition to disturbances in ventricular regulation [29]. Another important observation of the differences in cardiac autonomic modulation between the sexes can be exemplified by women with Polycystic Ovary Syndrome. In this group of women, there is a significant increase in the main male hormone, testosterone, positively correlated with the increased sympathetic autonomic component influence [30]. Thus, testosterone levels in men, and estrogens in women, are variables that could explain the sex differences found in the autonomic modulation of HRV, including in patients with SAH.
Other aspects that may influence the sympathetic autonomic modulation predominance in men involve body composition and the investigated blood parameters. Regarding body composition, we know that men have a higher volume of skeletal muscle mass. This greater muscle volume may result in a greater participation of sympathetic autonomic component in cardiovascular regulation [31]. The literature also shows that men would have a greater number of sympathetic ganglion neurons, when compared to women [32]. In our study, despite the almost similar anthropometric results, men tended to have higher BMI values and lower body fat percentage values, suggesting that this group had a higher percentage of lean mass. On the other hand, blood parameters were quite different. Women had higher values of HDL, and lower values of triglycerides and fasting glucose. In fact, these differences could justify the reduction of autonomic modulation in hypertensive men, but not in hypertensive women.
Two findings in our study are intriguing and point to the importance of the different hormonal characteristics of the sexes. The first is the significant reduction in the values of HRV vagal autonomic modulation in hypertensive men, characterized by HF component oscillations (men, 173 ± 30 ms²; women; 474 ± 64 ms²). While hypertensive women showed a reduction of half (normotensive, 1044 ± 160 ms²; hypertensive, 474 ± 64 ms²), men showed a reduction of almost 1/5 (normotensive, 635 ± 146 ms²; hypertensive 173 ± 30 ms²). In this case, it is possible that this reduction is related to lower BRS. It should be noted that in the normotensive group (men and women), there are no differences in BRS [10]. Everything indicates that SAH appears to induce greater damage in men, evidenced by a significant reduction in vagal participation in cardiovascular autonomic regulation. The second finding is that for the treatment with losartan, despite the blood pressure (BP) normalization, the cardiac autonomic modulation parameters were far below the desirable level, as noted above. This is worrisome, since HRV indexes are often used as morbidity and mortality predictors. [19] However, as our findings demonstrate, men are less protected, mainly because they exhibit an excessive drop in HF oscillations that correspond to vagal autonomic modulation. Finally, the significant reduction in the HF component of HRV may also be due, at least in part, to the metabolic misfit found in hypertensive men.
Perspective And Significance
Hypertensive women and men, even when treated with losartan, show reductions in HRV, when compared to normotensive volunteers. Despite systemic arterial hypertension, women and men have a different predominance of autonomic components over cardiac modulatory balance. Women are more dependent on vagal modulation, while men have a greater prevalence of the sympathetic autonomic component. Therefore, according to these findings, it is possible to suggest that men have higher cardiovascular risks, and that the possible causes of the differences found are the characteristics of sex hormones. However, further studies are needed to identify the precise mechanisms responsible for these findings.