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An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies.<\/jats:p>","DOI":"10.1152\/ajpheart.00859.2014","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T22:41:52Z","timestamp":1429310512000},"page":"H1476-H1498","source":"Crossref","is-referenced-by-count":197,"title":["Chronic stress impacts the cardiovascular system: animal models and clinical outcomes"],"prefix":"10.1152","volume":"308","author":[{"given":"Saeid","family":"Golbidi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson C.","family":"Frisbee","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West 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