Abstract
Upon stimulation with agonists and shear stress, the vascular endothelium of different vessels selectively releases several vasodilator factors such as nitric oxide and prostacyclin. In addition, vascular endothelial cells of many vessels regulate the contractility of the vascular smooth muscle cells through the generation of endothelium-dependent hyperpolarization (EDH). There is a general consensus that the opening of small- and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) is the initial mechanistic step for the generation of EDH. In animal models and humans, EDH and EDH-mediated relaxations are impaired during hypertension, and anti-hypertensive treatments restore such impairments. However, the underlying mechanisms of reduced EDH and its improvement by lowering blood pressure are poorly understood. Emerging evidence suggests that alterations of endothelial ion channels such as SKCa channels, inward rectifier K+ channels, Ca2+-activated Cl− channels, and transient receptor potential vanilloid type 4 channels contribute to the impaired EDH during hypertension. In this review, we attempt to summarize the accumulating evidence regarding the pathophysiological role of endothelial ion channels, focusing on their relationship with EDH during hypertension.
Highlights
Endothelial cells play a critical role in the regulation of vascular tone through the release of several vasorelaxing and vasoconstricting factors [1]
We recently demonstrated that the opening of endothelial TRPV4 channels and the downstream activation of SKCa and IKCa are involved in ACh-induced, Endothelium-Dependent Hyperpolarization (EDH)-mediated responses in superior mesenteric arteries of rats [46]
Endothelium-dependent hyperpolarization (EDH) and EDH-mediated relaxation are impaired during prolonged hypertension
Summary
Endothelial cells play a critical role in the regulation of vascular tone through the release of several vasorelaxing and vasoconstricting factors [1]. Because their study was conducted without inhibiting the synthesis of NO and prostaglandins (both of which produce endothelium-dependent smooth muscle hyperpolarization in certain vascular beds [57,58]), it was difficult to accurately evaluate the relative contribution of EDH to impaired ACh-induced hyperpolarization during hypertension in their rat hypertension model. In a study using the superior mesenteric arteries of SHR, Fujii et al demonstrated that ACh-induced, endothelium-dependent hyperpolarization and relaxation resistant to inhibitors of NO and prostaglandin synthesis (and EDH-mediated responses), were decreased in SHR compared with normotensive Wistar-Kyoto (WKY) rats [40]. We summarize the ionic mechanisms in vascular endothelial cells contributing to the reduced EDH during hypertension
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