Endothelin-I and angiotensin II inhibit arterial voltage-gated K+ channels through different protein kinase C isoenzymes

Rainbow, Richard D.; Norman, Robert I.; Everitt, Diane E.; Brignell, Jennifer L.; Davies, Noel W.; Standen, N B

doi:10.1093/cvr/cvp143

Cited by 49 publications

(60 citation statements)

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“…Angiotensin II is known to inhibit K v channels. 40 Together, these findings may explain the lack of vasodilatory effects of PAME in the aortic muscle ring of the SHR ( Figure 7C) and that antihypertensive effect of losartan is due in part to its blocking AII effects and preserving PAME-induced vasorelaxation. …”

mentioning

confidence: 82%

Role of Perivascular Adipose Tissue–Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension

Lee

Chang²,

Chiang³

et al. 2011

Circulation

143

136

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Background-Perivascular adipose tissue (PVAT)-derived relaxing factor (PVATRF) significantly regulates vascular tone. Its chemical nature remains unknown. We determined whether palmitic acid methyl ester (PAME) was the PVATRF and whether its release and/or vasorelaxing activity decreased in hypertension. Methods and Results-Using superfusion bioassay cascade technique, tissue bath myography, and gas chromatography/mass spectrometry, we determined PVATRF and PAME release from aortic PVAT preparations of Wistar Kyoto rats and spontaneously hypertensive rats. The PVAT of Wistar Kyoto rats spontaneously and calcium dependently released PVATRF and PAME. Both induced aortic vasorelaxations, which were inhibited by 4-aminopyridine (2 mmol/L) and tetraethylammonium 5 and 10 mmol/L but were not affected by tetraethylammonium 1 or 3 mmol/L, glibenclamide (3 mol/L), or iberiotoxin (100 nmol/L). Aortic vasorelaxations induced by PVATRF-and PAME-containing Krebs solutions were not affected after heating at 70°C but were equally attenuated after hexane extractions. Culture mediums of differentiated adipocytes, but not those of fibroblasts, contained significant PAME and caused aortic vasorelaxation. The PVAT of spontaneously hypertensive rats released significantly less PVATRF and PAME with an increased release of angiotensin II. In addition, PAME-induced relaxation of spontaneously hypertensive rats aortic smooth muscle diminished drastically, which was ameliorated significantly by losartan. Conclusions-We found that PAME is the PVATRF, causing vasorelaxation by opening voltage-dependent K ϩ channels on smooth muscle cells. Diminished PAME release and its vasorelaxing activity and increased release of angiotensin II in the PVAT suggest a noble role of PVAT in pathogenesis of hypertension. The antihypertensive effect of losartan is attributed partly to its reversing diminished PAME-induced vasorelaxation. (Circulation. 2011;124:1160-1171.) Key Words: angiotensin II Ⅲ fatty acids Ⅲ hypertension Ⅲ potassium ion channels Ⅲ vasomotor tone Ⅲ vasorelaxation Ⅲ losartan T he systemic blood vessels are surrounded by various amounts of perivascular adipose tissue (PVAT). Since the first report by Soltis and Cassis in 1991 that PVAT attenuated contraction of aortic rings to norepinephrine, 1 it has been well accepted that the anticontractile effect of PVAT is due to release of relaxing factor(s) from these adipocytes. 2 The vasodilation induced by PVAT-derived relaxing factor (PVATRF) is independent of the endothelium, cyclooxygenase, or cytochrome P450 pathway. 2,3 The general consensus is that PVATRFinduced vasodilation is due to opening of potassium channels on the smooth muscle cells. [2][3][4][5] The chemical identity of the PVATRF, however, remains unknown. Clinical Perspective on p 1171Our recent studies using superfusion bioassay cascade technique have demonstrated release of an endogenous potent vasodilator, palmitic acid methyl ester (PAME), from the superior cervical ganglion and retina of the rat. 6,7 Because PAME is hydro...

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mentioning

confidence: 82%

Role of Perivascular Adipose Tissue–Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension

Lee

Chang²,

Chiang³

et al. 2011

Circulation

143

136

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“…PKC activation not only mediates ET-1-induced vascular contraction (2,16,123) and regulates ET-1 receptors expression (112), but is intimately linked to ET-1-mediated regulation of hypertrophy, growth, proliferation, and survival in vascular smooth muscle cells (12). PKC activation (PKC-␦), via phosphorylation of STAT3, also mediates ET-1-induced decreases in arterial eNOS protein levels and NO generation (150) as well as ET-1-induced vascular formation of superoxide anion (103).…”

Section: Signaling Pathways Activated By Et-1 That Can Be Modified Bymentioning

confidence: 99%

O-GlcNAcylation: a novel pathway contributing to the effects of endothelin in the vasculature

Lima

Giachini

Hardy

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Glycosylation with Olinked ␤-N-acetylglucosamine (O-GlcNAc) or O-GlcNAcylation on serine and threonine residues of nuclear and cytoplasmic proteins is a posttranslational modification that alters the function of numerous proteins important in vascular function, including kinases, phosphatases, transcription factors, and cytoskeletal proteins. O-GlcNAcylation is an innovative way to think about vascular signaling events both in physiological conditions and in disease states. This posttranslational modification interferes with vascular processes, mainly vascular reactivity, in conditions where endothelin-1 (ET-1) levels are augmented (e.g. salt-sensitive hypertension, ischemia/reperfusion, and stroke). ET-1 plays a crucial role in the vascular function of most organ systems, both in physiological and pathophysiological conditions. Recognition of ET-1 by the ET A and ETB receptors activates intracellular signaling pathways and cascades that result in rapid and long-term alterations in vascular activity and function. Components of these ET-1-activated signaling pathways (e.g., mitogen-activated protein kinases, protein kinase C, RhoA/Rho kinase) are also targets for O-GlcNAcylation. Recent experimental evidence suggests that ET-1 directly activates O-GlcNAcylation, and this posttranslational modification mediates important vascular effects of the peptide. This review focuses on ET-1-activated signaling pathways that can be modified by O-GlcNAcylation. A brief description of the O-GlcNAcylation biology is presented, and its role on vascular function is addressed. ET-1-induced O-GlcNAcylation and its implications for vascular function are then discussed. Finally, the interplay between O-GlcNAcylation and O-phosphorylation is addressed. endothelin receptor; vascular signaling; O-GlcNAc modification GLYCOSYLATION IS THE SITE-specific enzymatic addition of saccharides to proteins and lipids. There are many types of glycosylation, but great interest has been directed to O-GlcNAcylation, or glycosylation with O-linked ␤-N-acetylglucosamine or ␤-Olinked 2-acetamido-2-deoxy-D-glycopyranose (54,55,169). In this unusual form of protein glycosylation, a single sugar [␤-N-acetylglucosamine (O-GlcNAc)] is added to serine and threonine residues of nuclear or cytoplasmic proteins (54,55,169).Considering that almost every functional class of proteins is subject to O-GlcNAcylation (55, 177), this specific posttranslational modification has been implicated in several biological functions, including transcription or translation, stress responses, and energy metabolism. Proteins with an important role in vascular function are also targets for O-GlcNAcylation. Examples include endothelial nitric oxide (NO) synthase (eNOS), sarcoplasmic reticulum calcium (Ca 2ϩ )-ATPase (SERCA), phospholipase C (PLC), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and proteins involved in cytoskeleton regulation and microtubule assembly (22,55,177), indicating that this posttranslational modification may play an important role in vascular (...

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“…PKC enhances the contraction of vascular smooth muscle by L-type calcium channel phosporylation. The importance of PKC activation is proven by the fact that phorbol esters, a group of synthetic PKC activators, induce the contraction of vascular smooth muscle (14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells

et al. 2012

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Abstract. Cyclosporine belongs to the group of the most commonly used immunosuppressants. Hypertension occurs in approximately 30% of patients treated with this drug. However, the pathogenesis of this occurrence has not been explained to date. The purpose of our study was to clarify the mechanisms leading to the evolution of hypertension induced by cyclosporine A (CsA). We examined the changes in transmission within receptors and around the receptors. We also aimed to elucidate the mechanisms responsible for averting arterial hyperresponsiveness induced by the drug. Experiments were performed on isolated and perfused tail arteries of Wistar rats. Tissues surrounding the artery were removed and the proximal segment (length of 2-3 cm) was used for cannulation. Cannulated arteries were placed in a 20-ml glass chamber (vertical position). The contraction force in our model was measured by an increased degree of perfusion pressure with a constant flow rate (approximately 1 ml/min). The results showed that in the presence of CsA, the concentration-response curves/phenylephrine (PHE) curve shifted to the left. Cyclosporine increased the reactivity of the arteries to PHE. This effect was directly linked to the increase in the receptor reserve. The analysis of the reactivity of vascular smooth muscle showed that CsA increased the influx of calcium ions from the extracellular to the intracellular area. No difference was found between the contraction triggered by Bay-K8644 in the presence of CsA and the control probe. The increase in perfusion pressure induced by CsA was blocked by L-type calcium channel blockers (nifidipine and diltiazem). The results from our experiments show that CsA increases the reactivity of vessels to the effect of catecholamines. CsA also enhances signal transmission between G-protein coupled receptors (GPCRs) and calcium channels. The activation of protein kinase C also plays a significant role in this process. Our results suggest that the best choice for the pharmacotherapy of hypertension induced by CsA would be calcium channel antagonists.

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Endothelin-I and angiotensin II inhibit arterial voltage-gated K+ channels through different protein kinase C isoenzymes

Cited by 49 publications

References 46 publications

Role of Perivascular Adipose Tissue–Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension

Role of Perivascular Adipose Tissue–Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension

O-GlcNAcylation: a novel pathway contributing to the effects of endothelin in the vasculature

Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells

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