Risk estimates from population studies indicate that at least two-thirds of hypertension can be directly attributed to obesity [1,2]. In particular, central obesity has been consistently associated with hypertension and cardiovascular disease [3,4]. However, the precise mechanisms linking hypertension to obesity are not fully understood. Haemodynamic factors, neuroendocrine mechanisms and, most recently, adipose tissue-derived factors have been considered to play a role in the pathogenesis of obesity-related hypertension [5–7]. A high prevalence of hypertension in obese subjects has also been related to psychosocial factors, including chronic exposure to stress [8,9]. Recently, the hypothalamic–pituitary–adrenal axis was suggested to be a key mechanism linking obesity, hypertension and chronic stress .
In normal subjects, acute mental stress results in an increase of blood pressure and cardiac output, and a decrease of total peripheral resistance. Jern et al.  showed that central obesity is associated with higher systemic vascular resistance during mental stress. The relative contribution of cardiac output to the stress-induced increase in mean arterial pressure is inversely related to the waist-to-hip ratio, indicating that central obesity is characterized by vasoconstrictor response to mental stress . Furthermore, a haemodynamic stress response characterized by greater vasoconstriction and less cardiac activation has been associated with defeat-like rather than defense reaction [8,11]. Taken together, these findings provide compelling evidence for the idea that impaired systemic vasodilation in response to stress might be implicated in the link between obesity and hypertension.
In this issue of the journal, Agapitov et al.  provide new insights into the relationship between vascular function and stress in obesity. The authors demonstrate that both skeletal muscle and skin vasodilation responses to mental stress are impaired in obese normotensive subjects. Thus, the previously reported increase in systemic vascular resistance during mental stress in obese subjects might be explained by impaired vasodilation in different vascular beds. These important findings raise further questions about microcirculatory function in human obesity.
Previous studies have shown that both the degree of obesity (as defined by body mass index) and central distribution of body fat (as defined by waist-to-hip ratio) exert independent influences on haemodynamics. Body mass index is directly correlated to cardiac output and stroke volume, and inversely correlated to systemic vascular resistance . In contrast, central body fat distribution has been associated with lower cardiac output and higher total peripheral resistance . Therefore, it would be important to evaluate the relative contribution of central fat distribution to the impaired vasodilation observed by Agapitov et al. .
Cardiovascular responses to mental stress represent a complex interplay between the autonomic nervous system and cardiac and vessel function/structure. The mechanisms responsible for the observed defect in vasodilation in reponse to mental stress in obese subjects are not clear. As suggested by the authors, impairment of sympathetic neural mechanisms might be implicated. First, sympathetic withdrawal during mental stress might be attenuated. This would be expected on the basis of the previously reported impairment of baroreflex control of muscle sympathetic nervous activity in obese humans . Alternatively, microcirculatory responses in obese subjects might be blunted because of impaired β2-adrenergic-mediated vasodilatation. In the study by Agapitov et al., there was a clear trend (P = 0.07) towards a smaller heart rate (β1-mediated) increase during mental stress in obese subjects. The attenuated heart rate response to mental stress is suggestive of the possibility of decreased β-adrenergic responsiveness contributing to an impairment of vasodilation.
Several metabolic factors, including insulin and nitric oxide [14,15], might also contribute to the observed impairment of vasodilation in obese subjects. Although insulin sensitivity was not measured in the study by Agapitov et al., it is likely that most of the obese subjects were insulin resistant. There is increasing evidence that insulin resistance may influence haemodynamics through effects on vascular reactivity . Insulin resistance has been associated with an exaggerated blood pressure response to mental and physical stress . A recent study found a close correlation between skin blood flow and insulin sensitivity . Obesity may finally impair vasodilation during stress through increased activity of the systemic renin–angiotensin system , endothelial dysfunction  and increased levels of proinflamatory cytokines . Clearly, the importance of all these factors in stress-related impairment of vasodilation should be evaluated in future studies.
In the study by Agapitov et al., blood pressure elevation during mental stress was similar in obese and lean subjects, despite the impairment of vasodilation in the former group. This suggests that young obese individuals are able to ‘buffer’ this impairment via compensatory mechanisms. Ageing, structural vascular changes and coexisting diseases are all known to augment the pressor responses. Therefore, it is conceivable that an early impaired vasodilation found in young obese subjects might facilitate the future development of hypertension, especially in those individuals exposed to chronic stress. Weight loss has been shown to improve endothelial function , decrease sympathetic nerve activity  and improve baroreflex function . Whether weight reduction is also associated with improvement of vasodilation in response to mental stress remains to be determined.
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