Mechanisms of Action of Atrial Natriuretic Factor and C-Type Natriuretic Peptide

Amin, Janki; Carretero, Oscar A.; Ito, Sadayoshi

doi:10.1161/01.hyp.27.3.684

Cited by 32 publications

(25 citation statements)

References 19 publications

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“…That eNOS inhibition was found to attenuate the CNP-induced hyperpolarization suggests that CNP may increase the synthesis and release of NO in pulmonary microvasculature. This conclusion is supported by the work of Amin et al (2) and Brunner and Wolkart (5) in the renal and coronary arteries, respectively, and suggests that, in the pulmonary circulation, CNP may have a positive feedback autocrine function and increase the calcium-dependent secretion of other endothelium-derived vasodilators. We noted significant effect of CNP at the dose of 1 M. Although CNP causes vasorelaxation at lower doses in isolated pulmonary vessels, that effect is likely endothelium-independent (20).…”

Section: Discussionmentioning

confidence: 59%

“…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 -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 iberiotoxinsensitive, CNP-induced outward current was confirmed by perforated patch-clamping experiments.…”

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confidence: 99%

“…It has been suggested that the CNP-induced relaxation is mediated, in part, by the vascular endothelium in certain vascular beds (2,5). In addition to releasing NO, endothelial cells can alter vascular tone by hyperpolarization of the underlying smooth muscle cells.…”

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confidence: 99%

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Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization

Simon¹,

Harrington²,

Liu³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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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 DiBAC4(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 ϩ channel blockers, tetraethylammonium or iberiotoxin, the nonspecific cation channel blocker, La 3ϩ , or by depletion or repletion of extracellular Ca 2ϩ or K ϩ , 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 -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 iberiotoxinsensitive, 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.large-conductance calcium-activated potassium channels; ion channel C-TYPE NATRIURETIC PEPTIDE (CNP) is a highly conserved member of the natriuretic peptide family and an important, but controversial, regulator of vascular tone and blood pressure. CNP consists of 22 amino acid residues and shares a 17-amino acid disulfide ring structure with atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) (29). CNP functions as a paracrine hormone in both the pulmonary and systemic circulations and is expressed and secreted by vascular endothelial cells (17,35,37). Like ANP and BNP, CNP has been demonstrated to relax blood vessels in a number of vascular beds (8,14,20,39,40). Furthermore, CNP appears to have both anti-inflammatory (18, 26, 33) and anti-mitogenic (12, 18, 26) properties. Thus CNP may serve a potentially useful therapeutic agent, especially in the pulmonary circulation, where it has been found to attenuate both bleomycin-induced lung fibrosis and monocrotaline-induced pulmonary hypertension (18, 26). However, although the physiological effects of CNP are intriguing, the signaling mechanisms that underlie many of its vascular activities remain incompletely described.The physiological ...

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Section: Discussionmentioning

confidence: 59%

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confidence: 99%

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Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization

Simon¹,

Harrington²,

Liu³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Prostaglandins and NO contribute to the relaxation of renal afferent arterioles to CNP (Amin et al, 1996). Relaxations to CNP are larger in rings of canine coronary arteries without endothelium than those with endothelium (Wright et al, 1996).…”

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confidence: 99%

Endothelium-Derived Nitric Oxide Inhibits the Relaxation of the Porcine Coronary Artery to Natriuretic Peptides by Desensitizing Big Conductance Calcium-Activated Potassium Channels of Vascular Smooth Muscle

Liang

Au²,

Leung³

et al. 2010

J Pharmacol Exp Ther

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The present experiments investigated whether endothelium-derived mediators modulate the effect of natriuretic peptides in porcine coronary arteries. Rings with and without endothelium were suspended in organ chambers for isometric tension recording. Concentrationrelaxation curves to C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) were obtained during contractions to endothelin-1. Removal of the endothelium potentiated relaxations to both CNP and ANP. N thelium. CNP-induced relaxations were reduced by 8-bromoguanosine 3Ј,5Ј-cGMP (8-bromo-cGMP) to the same extent in rings with and without endothelium. There was no significant difference between the increased cGMP content caused by CNP in porcine coronary arteries with or without endothelium. In patch-clamp studies in porcine coronary arterial smooth muscle cells, the natriuretic peptide-mediated enhancement of the IBTX-sensitive big conductance calcium-activated potassium channel (BK Ca ) amplitude was reversed by SNP and 8-bromo-cGMP. These findings demonstrate that, in the porcine coronary artery, the opening of BK Ca and ATP-dependent potassium channels of the vascular smooth muscle contributes to CNP-mediated relaxations. Endothelium-derived and exogenous NO inhibit the direct relaxing effect of natriuretic peptides by desensitizing the response of the BK Ca s of the vascular smooth muscle to the generation of cGMP.

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“…O CNP é um potente fator vasodilatador do músculo liso de artérias e veias (Suga et al, 1992) e em alguns leitos vasculares esta vasodilatação depende do endotélio (Amin et al, 1996), mas independe de NO na elevação dos níveis de GMPc (Griffith, 2004). Este peptídeo promove hiperpolarização de membrana das células do músculo liso vascular de artérias isoladas, pela ativação do receptor NPR-C (Chauhan et al, 2003a;Garcha et al, 2006) e abertura de canais para potássio (K + ) de ampla condutância ativados por cálcio (BKCa) (Brunner et al, 2001;Madhani et al, 2003).…”

Section: Introductionunclassified

Modulação promovida pelo peptídeo natriurético tipo C sobre a resposta contrátil induzida pela fenilefrina em aorta torácica e artéria mesentérica de resistência isoladas de ratos submetidos ao choque séptico

Pernomian¹

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DEDICATÓRIA Aos meus pais, Luiz Antônio Pernomian e Eli ConceiçãoParaizo Pernomian, por todo o amor e dedicação empenhados para a realização dessa difícil conquista, durante todos esses anos. A minha irmã, Larissa Pernomian, pelo amor, apoio e compreensão em todos os momentos da minha vida, sendo sempre o meu exemplo e guia. Ao meu namorado, Alejandro Ferraz do Prado, que sempre esteve ao meu lado em todos os momentos, me apoiando, acreditando em mim e me dando forças para continuar em frente. In memoriam de Luana Pernomian, luz que ilumina e guarda nossos caminhos. AGRADECIMENTOSA Deus pela graça da vida e por todas as alegrias e experiências vividas ao longo desses anos. Por ter me dado paciência e sabedoria diante de todos os desafios.Aos meus pais, Luiz Antônio e Eli, pelo amor, carinho, apoio, dedicação integral e ensinamentos que me proporcionaram, não medindo esforços para que eu conseguisse alcançar meus objetivos sempre com muita coragem e força para vencer os obstáculos que surgissem em meu caminho.A minha irmã Larissa, que sempre esteve ao meu lado, sendo meu exemplo de vida, me protegendo quando era preciso, me ajudando nos momentos difíceis, compartilhando alegrias e tristezas, sendo minha companhia e por todos os ensinamentos durante toda a vida.Ao meu namorado Alejandro, que por tantas vezes esteve ao meu lado trabalhando e me ensinando, compartilhando comigo medos e incertezas, pelo apoio nas horas desafiadoras, pelo abraço nos momentos difíceis, pelo amor e carinho ao longo de todos esses dias.A minha orientadora, Prof.ª Dr.ª Lusiane Maria Bendhack, pelas oportunidades de aprendizado e crescimento pessoal e profissional, pela dedicação e confiança que foram essenciais para o desenvolvimento deste trabalho. O choque séptico é uma síndrome inflamatória sistêmica secundária a um processo infeccioso, no qual as disfunções das células endoteliais e do músculo liso vascular contribuem para suprimento sanguíneo insuficiente a órgãos vitais, com consequente hipotensão sistêmica, insuficiência múltipla de órgãos e morte. Em geral, nos pacientes com choque séptico, existe um desequilíbrio dos fatores hemodinâmicos, levando ao baixo débito cardíaco e vasodilatação, além da redução da resposta contrátil aos diferentes agonistas, nos quais a participação do óxido nítrico (NO), de NO-sintases (NOS) e do estresse oxidativo são evidentes. A contribuição do sistema de peptídeos natriuréticos é evidenciada nos pacientes e em animais submetidos à sepse severa ou ao choque séptico. O peptídeo natriurético tipo C (CNP) é um agente vasodilatador que leva ao relaxamento vascular pela produção de GMPc intracelular, NO, hiperpolarização de membrana das células do músculo liso vascular e redução da concentração citosólica de cálcio. O tratamento com antagonista de receptores NPR-A/B tornou os animais menos susceptíveis à sepse, com menor resposta hipotensora, melhora da contração a agonistas e redução do processo inflamatório e NO plasmático. Portanto, a hipótese do presente trabalho é que no modelo de choque séptico in...

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Mechanisms of Action of Atrial Natriuretic Factor and C-Type Natriuretic Peptide

Cited by 32 publications

References 19 publications

Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization

Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization

Endothelium-Derived Nitric Oxide Inhibits the Relaxation of the Porcine Coronary Artery to Natriuretic Peptides by Desensitizing Big Conductance Calcium-Activated Potassium Channels of Vascular Smooth Muscle

Modulação promovida pelo peptídeo natriurético tipo C sobre a resposta contrátil induzida pela fenilefrina em aorta torácica e artéria mesentérica de resistência isoladas de ratos submetidos ao choque séptico

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