Kv Channels Contribute to Nitric Oxide- and Atrial Natriuretic Peptide-Induced Relaxation of a Rat Conduit Artery

Tanaka, Yoshio; Tang, Guanghua; Takizawa, Kei; Otsuka, Kazuoki; Eghbali, Mansoureh; Song, Min; Nishimaru, Kazuhide; Shigenobu, Koki; Koike, Kenichi; Stefani, Enrico; Toro, Ligia

doi:10.1124/jpet.105.096115

Cited by 40 publications

(34 citation statements)

References 33 publications

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“…These findings were dispiriting since BK channel is abundantly expressed in rat aortic smooth muscle. 35) Our results also ruled out substantial involvement of other Ca a SK2 and SK3 channel inhibitor) and ChTX (10 −7 M, an IK channel inhibitor) (Fig. 3).…”

Section: Discussionmentioning

confidence: 74%

“…3). In the presence of 2×10 −3 M TEA, which comparatively inhibits selectively BK channel at this concentration, 35,36) DHA (10 −5 M)-induced relaxation was diminished to less than 50% in n=8 experiments of total n=15 experiments. However, 2×10 −3 M TEA did not show significant inhibitory effects in other n=7 experiments, and thus, averaged relaxant effect of DHA in the presence of this concentration of TEA was 49.6± 9.7% (n=15).…”

Section: Discussionmentioning

confidence: 99%

“…TEA at 10 −2 M interferes with several K + channel species, which include BK channel, K ATP channel, K v channels, and so on. 35,36) Since BK channel contribution was ruled out, possible role for K ATP channel was then investigated. For this purpose, glibenclamide is usually employed as a representative pharmacological tool to know the role for K ATP channel in tissue responses.…”

Section: Discussionmentioning

confidence: 99%

“…(an inhibitor for SK2 and SK3 channels) 34) ; 4-aminopyridine (10 −3 M) (an inhibitor of K v 1 family and K v 3 family) 35) ; tetraethylammonium (TEA, 10…”

Section: )mentioning

confidence: 99%

“…inhibitor at this concentration) 35,36) ; PNU-37883 A (10 −6 M) (an inhibitor for ATP-sensitive K (K ATP ) channel).…”

Section: )mentioning

confidence: 99%

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Pharmacological Evidence Showing Significant Roles for Potassium Channels and CYP Epoxygenase Metabolites in the Relaxant Effects of Docosahexaenoic Acid on the Rat Aorta Contracted with U46619

Sato

Chino

Nishioka

et al. 2014

Biological & Pharmaceutical Bulletin

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Docosahexaenoic acid (DHA) shows more pronounced relaxation when blood vessel is contracted with prostanoid receptor agonists than other stimulants. The present study was carried out to obtain information on the mechanisms underlying prostanoid receptor-selective relaxant action of DHA, particularly focusing on the possible roles for K channels and its CYP epoxygenase (EOX) metabolites. In endothelium-denuded rat thoracic aorta, DHA (10 5 M) almost completely relaxed U46619 (a thromboxane A 2 (TP) receptor agonist)-contracted muscle without substantially affecting noradrenaline (NA)-induced contraction. DHA-induced relaxation was not affected by a large conductance, calcium-and voltage-activated K (BK) channels inhibitor iberiotoxin (IbTX, 10 7 M) but was almost abolished by high-KCl (8 10 2 M) or 10 2 M tetraethylammonium (TEA) which non-selectively inhibits K channel activity. DHA also prominently relaxed U46619-contracted aorta even in the presence of CYP inhibitors (SKF525A or miconazole, each at 10 5 M). However, in the presence of these CYP inhibitors, the relaxant action of DHA was not affected by 10 2 M TEA. In supporting a significant role for CYP EOX metabolites in the blood vessel relaxation to DHA, 16,17-epoxy docosapentaenoic acid (16,17-EpDPE), but not 19,20-EpDPE, showed a potent relaxation in U46619-contracted aorta, and this action was significantly attenuated by 10 2 M TEA. The present findings suggest that the relaxant action of DHA shown in the rat aorta contracted through the stimulation with TP receptor is generated by DHA itself and its CYP EOX metabolites. The relaxant effect of DHA metabolites seems to be partly triggered by the activation of K channels though the role for BK channel is insignificant.Key words docosahexaenoic acid (DHA); blood vessel relaxation; rat aorta; thromboxane A 2 receptor (TP receptor); CYP epoxygenase (EOX) Intake of fish or fish oil as a supplement is known to protect against cardiovascular disorders including coronary heart diseases, 1-3) atherosclerosis 4,5) and stroke. 6) Epidemiological studies have also indicated dietary fish oil has a blood pressure-lowering effect in hypertensive patients though this effect is weak or not observed in normotensive individuals. 7-9)These cardiovascular-protective effects of fish oil are probably attributed to docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major n-3 polyunsaturated fatty acids (PUFAs) contained in fish oil, which show anti-inflammatory effects, reduction of platelet aggregation and of plasma triglycerides, 10,11) and so on. Of these two n-3 PUFAs, DHA may be superior to EPA as a cardiovascular protector since DHA produces more favorable improving effects on abnormal lipid profile, 12) thrombosis risk 13) and ambulatory blood pressure. 14)Although it remains poorly understood how DHA exerts its beneficial actions on the cardiovascular systems, its cardiovascular-protective effects may be partly attributed to blood vessel relaxant effects. As to this issue, we previously found out DHA more s...

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…(an inhibitor for SK2 and SK3 channels) 34) ; 4-aminopyridine (10 −3 M) (an inhibitor of K v 1 family and K v 3 family) 35) ; tetraethylammonium (TEA, 10…”

Section: )mentioning

confidence: 99%

“…inhibitor at this concentration) 35,36) ; PNU-37883 A (10 −6 M) (an inhibitor for ATP-sensitive K (K ATP ) channel).…”

Section: )mentioning

confidence: 99%

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Pharmacological Evidence Showing Significant Roles for Potassium Channels and CYP Epoxygenase Metabolites in the Relaxant Effects of Docosahexaenoic Acid on the Rat Aorta Contracted with U46619

Sato

Chino

Nishioka

et al. 2014

Biological & Pharmaceutical Bulletin

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Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

283

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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cGMP-Dependent Protein Kinases (cGK)

Hofmann¹,

Wegener²

2013

Methods in Molecular Biology

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cGMP-dependent protein kinases (cGK) are serine/threonine kinases that are widely distributed in eukaryotes. Two genes-prkg1 and prkg2-code for cGKs, namely, cGKI and cGKII. In mammals, two isozymes, cGKIα and cGKIβ, are generated from the prkg1 gene. The cGKI isozymes are prominent in all types of smooth muscle, platelets, and specific neuronal areas such as cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. The cGKII prevails in the secretory epithelium of the small intestine, the juxtaglomerular cells, the adrenal cortex, the chondrocytes, and in the nucleus suprachiasmaticus. Both cGKs are major downstream effectors of many, but not all, signalling events of the NO/cGMP and the ANP/cGMP pathways. cGKI relaxes smooth muscle tone and prevents platelet aggregation, whereas cGKII inhibits renin secretion, chloride/water secretion in the small intestine, the resetting of the clock during early night, and endochondral bone growth. This chapter focuses on the involvement of cGKs in cardiovascular and non-cardiovascular processes including cell growth and metabolism.

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Kv Channels Contribute to Nitric Oxide- and Atrial Natriuretic Peptide-Induced Relaxation of a Rat Conduit Artery

Cited by 40 publications

References 33 publications

Pharmacological Evidence Showing Significant Roles for Potassium Channels and CYP Epoxygenase Metabolites in the Relaxant Effects of Docosahexaenoic Acid on the Rat Aorta Contracted with U46619

Pharmacological Evidence Showing Significant Roles for Potassium Channels and CYP Epoxygenase Metabolites in the Relaxant Effects of Docosahexaenoic Acid on the Rat Aorta Contracted with U46619

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

cGMP-Dependent Protein Kinases (cGK)

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