Vascular response to stress in health and disease

The body's vasculature plays a critical role in the development of functional and structural alterations responsible for tissue and organ damage in laboratory animals and human subjects during illness and senescence, and in response to stress. Components of the vasculature, namely, major arteries such as the aorta, smaller arteries, arterioles, capillaries, post-capillary venules, and collecting central veins, all serve as conduits through which vital substrates are delivered to cellular masses and/or waste products are removed. A number of physical and neurohumoral agents known to be responsive to stress stimuli exert functional control over the vasculature. Both physical and emotional stress have been found to cause significant hemodynamic alterations. Large artery rigidity, for instance, develops rapidly following stress-induced activation of the autonomic nervous system. Associated with this process is increased release into the circulation of catecholamines and angiotensin-II. At the same time, insulin resistance develops, accompanied by nitric oxide release and changes in the immune system. The response of large arterial conduits to stress is characterized by increased pulse pressure, which in turn affects the endothelium of the arterial vessels responsible for determining total peripheral resistance. Microcirculation networks, where a large fraction of the blood volume is contained, are affected as well, and the blood in them is subject to redistribution into adjacent interstitial fluid compartments. Changes in endothelial permeability, secondary to variations in pulse pressure, can lead to interstitial edema and changes in the physicochemical properties of interstitial compartments. These changes give rise to alterations in the traffic of substrates and waste products between blood and cells. This sequence of events also takes place in the vasa vasorum microcirculation that nourishes large arteries, and likely contributes to remodeling of the vascular wall and to atherogenesis. The contribution of large artery rigidity to the morbidity and mortality associated with arterial hypertension, diabetes mellitus, heart failure, and terminal uremia, is relatively well established in human populations. In addition, it appears that aortic rigidity precedes the development of arterial hypertension in the spontaneously hypertensive rat (SHR) model, as well as in individuals with borderline hypertension. The fact that some of the functional and structural vascular alterations produced by stress are reversible reinforces the importance of developing behavioral techniques and pharmacologic agents that can successfully interrupt this pathological sequence of events.