Abnormalities of vascular ion channels during hypertension

Abstract

Homeostasis of vascular tone in small arteries and arterioles relies on the balance between Ca 2+-dependent activation of vascular smooth muscle cells (VSMCs) and the vasodilator infl uences that counteract it. During the development of hypertension, the homeostasis of vascular tone is disrupted as pathophysiological events impinging on VSMCs promote vasoconstriction, rises in peripheral vascular resistance, and elevation of blood pressure. One critical process that contributes to hypertension is the “remodeling” of ion channels in the plasma membrane of VSMCs, which increases cell excitability. Most studies suggest that elevation of blood pressure is associated with a profound loss of voltage-gated K + channels encoded by several gene families. The loss of K + channels causes depolarization of VSMCs, opening of voltage-sensitive Ca 2+ channels, Ca 2+ infl ux and accentuated vasoconstriction. In tandem, even short-term elevations of blood pressure promote the expression of voltage-sensitive Ca 2+ channels in VSMCs, effectively increasing the number of pathways for Ca 2+ infl ux and Ca 2+-dependent activation of contractile proteins. Drawing on fi ndings from many laboratories, this chapter will review evidence for the induction of abnormalities of vascular K + and Ca 2+ channels during hypertension and discuss mechanisms that may mediate this process. New areas of investigation that may spur us to reconsider current dogma or provide important clues to the process of ion channel remodeling during hypertension also will be discussed.