Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels

Abstract

Several new concepts have emerged in relation to mechanisms that contribute to regulation of the cerebral circulation. This review focuses on some physiological mechanisms of cerebral vasodilatation and alteration of these mechanisms by disease states. One mechanism involves release of vasoactive factors by the endothelium that affect underlying vascular muscle. These factors include endothelium-derived relaxing factor (nitric oxide), prostacyclin, and endothelium-derived hyperpolarizing factor(s). The normal vasodilator influence of endothelium is impaired by some disease states. Under pathophysiological conditions, endothelium may produce potent contracting factors such as endothelin. Another major mechanism of regulation of cerebral vascular tone relates to potassium channels. Activation of potassium channels appears to mediate relaxation of cerebral vessels to diverse stimuli including receptor-mediated agonists, intracellular second messenger, and hypoxia. Endothelial- and potassium channel-based mechanisms are related because several endothelium-derived factors produce relaxation by activation of potassium channels. The influence of potassium channels may be altered by disease states including chronic hypertension, subarachnoid hemorrhage, and diabetes.

Nox2-Derived Reactive Oxygen Species Mediate Neurovascular Dysregulation in the Aging Mouse Brain

“…These observations provide the first demonstration that aging impairs not only endotheliumdependent relaxation but also neurovascular coupling, and that these cerebrovascular alterations are mediated by Nox2-derived ROS. The findings of this study cannot be attributed to differences in arterial pressure or blood gases, factors that have profound effects on CBF (Faraci and Heistad, 1998), because these variables were carefully controlled and did not differ among the groups of mice studied. Furthermore, the observations of this study cannot be attributed to age-related differences in the sensitivity to anesthesia leading to a generalized depression in cerebrovascular reactivity, because only selected CBF responses are attenuated in older mice.…”

“…Aging is associated with a reduction in resting cerebral blood flow (CBF) and a dysfunction of the mechanisms regulating the cerebral circulation (Faraci and Heistad, 1998;Farkas and Luiten, 2001). For example, the cerebrovascular relaxation induced by endothelium-dependent vasodilators, such as acetylcholine, is impaired in large and small cerebral arteries of older animals (Mayhan et al, 1990;Paterno et al, 1994) (for a review, see Faraci and Heistad, 1998). Furthermore, the increases in CBF induced by activation of central cholinergic pathways, hypercapnia, hypoxia, or hypotension are attenuated (Hoffman et al, 1981(Hoffman et al, , 1984(Hoffman et al, , 1982Sato et al, 2002).…”

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…However, using scanning electron microscopy to illustrate endothelial surface alterations, increased frequency of microvilli can be observed during periods of transient forebrain ischemia (Dietrich et al, 1984). Because the vascular endothelium plays an important role in blood-brain barrier (BBB) maintenance as well as to responsiveness to vasoactive substances (Faraci and Heistad, 1998), the effects of trauma and ischemia on endothelial function is currently a critical area of investigation (del Zoppo and Mabuchi, 2003). Increased vascular permeability is observed in many models of brain ischemia (Chan et al, 1984;del Zoppo, 1997;Hatashita and Hoff, 1990).…”

Cerebral Blood Flow and Autoregulation After Pediatric Traumatic Brain Injury

“…Activation of K + channels, principally K ATP , and calcium-sensitive channel, is an important mechanism for cerebral vasodilation and increases K + efflux, producing hyperpolarization of vascular muscle. Hyperpolarization then decreases the probability of opening of voltage dependent calcium channels, and relaxes smooth muscle [121]. Calcitonin gene related peptides (CGRP) activate K ATP channels, and nerve fibers containing CGRP which innervate pial arteries [122].…”