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• W2018575893 abstract "C-type natriuretic peptide (CNP) has a demonstrated hyperpolarizing effect on vascular smooth muscle cells. However, its autocrine function, including its electrophysiological effect on endothelial cells, is not known. Here, we report the effect of CNP on the membrane potential ( E m ) of pulmonary microvascular endothelial cells and describe its target receptors, second messengers, and ion channels. We measured changes in E m using fluorescence imaging and perforated patch-clamping techniques. In imaging experiments, samples were preincubated in the potentiometric dye DiBAC 4 (3), and subsequently exposed to CNP in the presence of selective inhibitors of ion channels or second messengers. CNP exposure induced a dose-dependent decrease in fluorescence, indicating that CNP induces endothelial cell hyperpolarization. CNP-induced hyperpolarization was inhibited by the K + channel blockers, tetraethylammonium or iberiotoxin, the nonspecific cation channel blocker, La 3+ , or by depletion or repletion of extracellular Ca 2+ or K + , respectively. CNP-induced hyperpolarization was also blocked by pharmacological inhibition of PKG or by small interfering RNA (siRNA)-mediated knockdown of natriuretic peptide receptor-B (NPR-B). CNP-induced hyperpolarization was mimicked by the PKG agonist, 8-bromo-cGMP, and attenuated by both the endothelial nitric oxide synthase (eNOS) inhibitor, N ω -nitro-l-arginine methyl ester (l-NAME), and the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one. Presence of iberiotoxin-sensitive, CNP-induced outward current was confirmed by perforated patch-clamping experiments. We conclude that CNP hyperpolarizes pulmonary microvascular endothelial cells by activating large-conductance calcium-activated potassium channels mediated by the activation of NPR-B, PKG, eNOS, and sGC." @default.
• W2018575893 created "2016-06-24" @default.
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• W2018575893 date "2009-02-01" @default.
• W2018575893 modified "2023-09-25" @default.
• W2018575893 title "Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization" @default.
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• W2018575893 doi "https://doi.org/10.1152/ajplung.90303.2008" @default.
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