Sympathetic System-Related Artery Stiffness.

In the present issue of Hypertension, Holwerda et al investigated the influence of the sympathetic nervous system on different indices of arterial stiffness in healthy subjects at a resting state and after an acute increase of sympathetic drive via lower body negative pressure. The findings of this study were novel and of clinical importance because of the methodology that was used and the integration of diverse aspects of mechanical vascular properties. Furthermore, confounding parameters in previous studies were also addressed. Overall, this article improves our understanding of the complex pathways that modulate arterial stiffening in humans. Vascular ageing is characterized by increased pulse wave velocity (PWV) and unfavorable modulation of arterial compliance. There is a strong correlation of increased arterial stiffness with adverse renal, brain, and cardiovascular outcomes. However, the identification of parameters that influence the arterial tone and promote unfavorable alterations of vascular function and structure remains an unmet need. Holwerda et al performed meticulous methodological steps to execute a refined protocol and found that the resting muscle sympathetic nerve activity (MSNA) was related to central and peripheral artery stiffness, as well as carotid compliance (Figure). Interestingly, after accounting for gender, the blood pressure (BP) and heart rate did not alter the association of MSNA with carotid-femoral PWV and carotid compliance. Although previous reports suggest that the link between BP and MSNA was more pronounced in aged females than in males, there were no gender differences in the association of resting MSNA with carotid-femoral PWV nor carotid properties. Previous studies have elegantly shown that MSNA, which is a precise and reproducible measure of sympathetic nervous system activity, increases with age. After controlling for age in the present study, the associations of sympathetic drive with measures of arterial stiffness lose their independent value.Along these lines, because of a link between MSNA and BP in subjects over 40 years compared with the lack of association in younger subjects, studies on the potential connection of the sympathetic nervous drive with BP regulation and stiffness can be promising and informative. The available data on the relationship between acute increases in MSNA and changes in arterial stiffness are still scarce. A major point to overcome is the influence of BP alterations on arterial properties by experimentally modifying MSNA. The lower body negative pressure resulted in increased MSNA and vasoconstriction with no changes in mean arterial pressure. The independent relationship between BP and MSNA augmentation on the central and peripheral stiffness suggests an additional pathophysiological pathway between sympathetic nervous system activation and vascular properties. Interestingly, age did not alter the MSNA response to lower body negative pressure. The magnitude of the augmentation of central PWV in this test at −15 and −30 mm Hg were 0.8 and 1.3 m/s, respectively, in young subjects and 0.5 and 1 m/s, respectively, in middle-aged and older participants. These increases in PWV correspond to heightened risk because an increase of 1 m/s in stiffness corresponds to significantly augmented cardiovascular morbidity and mortality. The remaining link of MSNA with PWV during the lower body negative pressure challenge further underlines the involvement of the sympathetic system in regulating arterial stiffness even in the acute setting, suggesting that PWV and carotid compliance are not simply mediated by innate properties of the vessel wall but also by an adrenergic tone. Whether these intermittent changes of MSNA during everyday life via enhanced BP variations result in higher risk as well as the establishment of a more unfavorable structure and function of central and peripheral arterial beds chronically remains to be determined in future studies (Figure). Younger subjects exhibit a reduction in carotid compliance along with an MSNA increase, while in older participants, there were no changes in compliance regardless of a comparable augmentation level of MSNA. Moreover, the relationship between MSNA and the carotid compliance coefficient was evident only at a lower body negative pressure of −30 mm Hg. This could be attributed to the diverse parameters influencing carotid artery remodeling and atherosclerotic processes compared to central and other peripheral arterial beds. The study by Holwerda et al is a robust one with sound results that clarified challenging concepts of sympathetic nervous system regulatory effects on arterial stiffness. However, there were some limitations in this study. The participants were not screened for obstructive sleep apnea, which can influence the sympathetic tone; therefore, the results may The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the First Cardiology Clinic, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. Correspondence to Costas Tsioufis, 114 Vas.Sofias Ave, 11527 Athens, Greece. Email ktsioufis@hippocratio.gr Sympathetic System–Related Artery Stiffness Understanding the Gordian Knot of Vascular Ageing