Endothelial Function and Hemodynamic Responses During Mental Stress ANDREW SHERWOOD,PHD, KRISTY JOHNSON, BA, JAMES A. BLUMENTHAL,PHD, AND ALAN L. HINDERLITER, MD Objective: The hemodynamic basis of blood pressure responses during psychological stress shows striking indi- vidual differences that share an interesting similarity with risk for cardiovascular disease. Factors accounting for these individual differences are poorly understood. The present study examined the relationship of vascular endothelial function to stress-induced hemodynamic responses. Methods: Subjects were 40 healthy men and women, aged 25 to 44 years. Hemodynamic responses were assessed during exposure to a battery of four diverse laboratory stressors. Endothelium-dependent arterial dilation (EDAD) was measured by ultrasound imaging of the brachial artery in response to reactive hyperemia. Results: High EDAD response was associated with lower resting systolic (p  .01) and diastolic blood pressure (p  .05). EDAD response was unrelated to blood pressure responses during stress. However, systemic vascular resistance responses during laboratory stress were significantly greater (p  .02) for individuals with low EDAD responses. Conclusions: Exaggerated systemic vascular resistance responses during stress may reflect endothelial dysfunction. This association may help explain the growing evidence of a relationship between stress hemodynamics and cardiovascular disease risk. The nature of this association is discussed in terms of a possible interplay between the sympathetic nervous system and the endothelium in regulation of vascular tone. Key words: endothelium, hemodynamics, stress, sympathetic nervous system, ultrasound. CHD = coronary heart disease; SVR = systemic vascu- lar resistance; HR = heart rate; SNS = sympathetic nervous system; EDAD = endothelium-dependent ar- terial dilation; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial pres- sure; CI = cardiac index; SVRI = systemic vascular resistance index; INTRODUCTION Exaggerated blood pressure responses to stress have been associated with increased risk for the develop- ment of CHD and hypertension (1– 4). More recently, the examination of hemodynamic factors has provided new insights into the potential mechanisms by which elevated blood pressure responses may contribute to this increased risk. For example, cardiovascular acti- vation during stress has been described in terms of cardiac output and SVR alterations that give rise to pressor responses. The clinical significance of specific hemodynamic response patterns is suggested by grow- ing evidence that individuals at increased risk for CHD exhibit characteristic hemodynamic responses. For ex- ample, African American men, who are at high risk for the development of CHD and hypertension, tend to exhibit greater contributions of SVR to blood pressure increases during exposure to laboratory stressors (5–7), whereas premenopausal women, who are at lower risk than men for CHD, exhibit a lower SVR contribution to blood pressure responses during stress (7). Recently, it was also shown that mental stress–induced myocar- dial ischemia is associated with a significant increase in SVR and relatively minor increases in HR and rate pressure product compared with ischemia induced by exercise (8). Systemic vascular tone is regulated by a number of systems. Neuroendocrine regulation, particularly the SNS, seems to play a prominent role in regulating vascular tone during mental stress. Both SNS activa- tion and the sensitivity of adrenergic receptors in the vasculature may contribute to changes in vasomotor tone and SVR during stress (5, 9, 10). Another fast- responding vascular regulatory system is the endothe- lial system. Among the substances released by the endothelium is nitric oxide, an endothelium-derived relaxing factor that is a fast-acting vasodilator of short duration, which is important in the regulation of arte- rial vasomotor tone and therefore SVR. Celermajer et al. (11) recently developed a noninvasive ultrasound methodology to examine endothelial function. This novel technique assesses the magnitude of EDAD elic- ited by reactive hyperemia. The magnitude of the EDAD response is used as a direct index of the func- tional status of the endothelium. Using this technique, it has been shown that compromised endothelial func- tion is associated with advancing age and is also char- acteristic of patients with CHD, cigarette smokers, and children with a family history of hyperlipidemia (11). To date, only one study has explored the association between EDAD and cardiovascular stress responses (12). The study measured the EDAD response in ado- lescents and found it to be directly related to cardio- vascular fitness and inversely related to SBP reactivity to stress. However, the stressors used in that study From the Duke University Medical Center, Durham, North Caro- lina, and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Address reprint requests to: Andrew Sherwood, PhD, Box 3119, Duke University Medical Center, Durham, NC 27710. Email: sherw002@mc.duke.edu. Received for publication October 23, 1998; revision received Jan- uary 20, 1999. 365 Psychosomatic Medicine 61:365–370 (1999) 0033-3174/99/6103-0365 Copyright © 1999 by the American Psychosomatic Society