Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

Davie, Christina; Kubo, Masahiro; Standen, N B

doi:10.1038/sj.bjp.0702232

Cited by 25 publications

(17 citation statements)

References 39 publications

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“…In addition, comparative studies show that relaxation responses to nicorandil are inhibited significantly by the K ATP blocker GLM, but not by the other K + -channel blocker. These findings are in agreement with previous reports (43,44).…”

Section: Discussionsupporting

confidence: 83%

“…These findings show that FLNT and nicorandil exhibit a dual mechanism of action acting partly as a nitrate and partly as a K + -channel opener. Our findings of two pathways for relaxation by nicorandil are consistent with two previous reports (43,44), while not consistent with other observations using piglet mesenteric arteries pre-contracted by noradrenaline (47). The reasons of the variable contribution of K ATP channel opening and stimulation of sGC on nicorandil-induced relaxation depend on the differences in the animal species, tissues, size of vessels, and agonist studied (48).…”

Section: Discussionsupporting

confidence: 82%

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Involvement of Guanylate Cyclase and K+ Channels in Relaxation Evoked by Ferulate Nitrate in Rat Aorta Artery

Wang¹,

Xu²,

Wang³

et al. 2012

J Pharmacol Sci

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Abstract. Vasorelaxant properties of N-2-(ferulamidoethyl)-nitrate (ferulate nitrate, FLNT), a newly synthesized nitrate, were compared with those of isosorbide dinitrate, nicorandil, nitroglycerin, and 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) in rat aorta pre-contracted by phenylephrine. FLNT produced vasorelaxation in a concentration-dependent manner (0.1 -100 μM). The degree of relaxation induced by FLNT was similar to that induced by isosorbide dinitrate. In addition, removal of endothelium did not affect the relaxant effect of FLNT. FLNT caused a rightward shift of the cumulative concentration-response curves of phenylephrine and reduced the maximal efficacy of contraction. 1H-[1,2,4]Oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and K + -channel blockers charybdotoxin (CHT, 0.1 μM) and BaCl 2 (1 μM) reduced the relaxant effect of FLNT in the endothelium-denuded arteries, whereas glibenclamide (1 μM) and 4-aminopyridine (1 mM) failed to influence FLNT-induced vasorelaxation. Furthermore, in the presence of ODQ, both CHT (0.1 μM) and BaCl 2 (1 μM) still significantly reduced the relaxation evoked by FLNT. Pretreatment of vessels with hydroxocobalamin, a nitric oxide scavenger, abolished the FLNT effect. These findings demonstrate that FLNT induces relaxation of the rat aorta rings endothelium-independently. Furthermore, we demonstrated that FLNT-induced vasorelaxation is related to its stimulation of soluble guanylate cyclase and activation of K + channels.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 82%

Involvement of Guanylate Cyclase and K+ Channels in Relaxation Evoked by Ferulate Nitrate in Rat Aorta Artery

Wang¹,

Xu²,

Wang³

et al. 2012

J Pharmacol Sci

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“…30 -32 In rat mesenteric arteries, small-conductance K ATP (K NDP ) channels (Ϸ25 pS, in symmetric high K ϩ ) have been identified that are regulated by nucleoside diphosphates (UDP or GDP) and ATP acting from the inside. 33,34 The molecular identity of the aortic and mesenteric K ATP channels is not absolutely established. Two Kir6.x subunits have been cloned to date: Kir6.1 and Kir6.2 that differ in their single channel conductance.…”

Section: Discussionmentioning

confidence: 99%

Visceral Periadventitial Adipose Tissue Regulates Arterial Tone of Mesenteric Arteries

et al. 2004

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Abstract-Periadventitial adipose tissue produces vasoactive substances that influence vascular contraction. Earlier studies addressed this issue in aorta, a vessel that does not contribute to peripheral vascular resistance. We tested the hypothesis that periadventitial adipose tissue modulates contraction of smaller arteries more relevant to blood pressure regulation. We studied mesenteric artery rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared with vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K ϩ -containing solutions (60 mmol/L) was similar in vessels with and without periadventitial fat. The K ϩ channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K ϩ -containing solutions (60 mmol/L), suggesting that K ϩ channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anticontractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayed-rectifier K ϩ (K v ) channels with 4-aminopyridine (2 mmol/L) or 3,4-diaminopyridine (1 mmol/L). Blocking other K ϩ channels with glibenclamide (3 mol/L), apamin (1 mol/L), iberiotoxin (100 nmol/L), tetraethylammonium ions (1 mmol/L), tetrapentylammonium ions (10 mol/L), or Ba 2ϩ (3 mol/L) had no effect. Longitudinal removal of half the perivascular tissue reduced the anticontractile effect of fat by almost 50%, whereas removal of the endothelium had no effect. We suggest that visceral periadventitial adipose tissue controls mesenteric arterial tone by inducing vasorelaxation via K v channel activation in vascular smooth muscle cells. Key Words: muscle, smooth Ⅲ mesenteric arteries Ⅲ obesity Ⅲ hypertension, obesity P eriadventitial adipose tissue is routinely removed for contraction studies on isolated blood vessels. Soltis and Cassis demonstrated that periadventitial fat significantly attenuates vascular responsiveness of rat isolated aortic rings to norepinephrine. 1 We confirmed the inhibitory action of periadventitial fat on aortic contraction. However, we also found that the effect is antagonized by depolarizing external high K ϩ solutions and partly by glibenclamide, suggesting that the anticontractile effects of fat are mediated in part by opening of ATP-dependent K ϩ (K ATP ) channels in aortic smooth muscle cells. 2 The action was not dependent on NO synthesis or endothelium. The anticontractile effects did not require the cyclooxygenase or P450 pathway, activation of adenosine receptors, or functional leptin receptors. 2 However, we found that relaxation was induced by a transferable adipocytederived relaxing factor (ADRF) released from periadventitial adipose tissue. 2 The results were not obtained in vessels that contribute to peripheral vascular re...

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“…Nicorandil acts on both sarcolemmal and mito-KATP channels, 40 and also has a nitrate effect. 41 The effect of diazoxide was completely blocked by 5-HD, but its effect on nicorandil was not complete, as shown by Fig 4. This may be attributed to its combined effect, although it was small in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ischemic Preconditioning and Mitochondrial KATP Channel Openers on Chronic Left Ventricular Remodeling in the Ischemic-Reperfused Rat Heart.

Dairaku

Miura

Harada

et al. 2002

Circ J

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brief episode of ischemia -reperfusion reduces the size of the infarct caused by a subsequent longer ischemia -reperfusion insult. This phenomenon was first reported by Murry et al 1 and termed ischemic preconditioning (IP). The underlying mechanism of this phenomenon has been intensively investigated and one of the crucial mechanisms is the opening of the mitochondrial ATP-sensitive potassium (mito-KATP) channels. [2][3][4] In order to mimic IP, the effect of mito-KATP channel openers has been investigated and these agents result in reduction of infarct size. [5][6][7][8][9][10][11][12] However, the effect of IP and mito-KATP channel openers on chronic left ventricular (LV) remodeling has not been clarified yet. LV remodeling is a major determinant of prognosis after myocardial infarction 13 and it may be determined by the infarct size and could be modified by drugs such as angiotensin-converting enzyme inhibitors. 14 Thus, assessing LV remodeling is an important evaluation of whether or not interventions such as IP or mito-KATP channel openers are really effective. Furthermore, the reperfusion conditions, such as the no reflow phenomenon, may modify the infarct size and thus the LV remodeling in the chronic state. Therefore, the purpose of the present study was to investigate the effect of IP and mito-KATP channel openers on the extent of LV remodeling as assessed by the pressure -volume relationship, and to assess the correlation between infarct size and LV remodelCirculation Journal Vol.66, April 2002 ing during the chronic stage. MethodsAll experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23) and were approved by the Animal Research Committee of Yamaguchi University School of Medicine. Surgical PreparationMale Sprague-Dawley rats (280-330 g) were anesthetized by intraperitoneal injection of sodium pentobarbital (60 mg/kg). Additional anesthesia was given during the experiment as required. After tracheal intubation, the rats were ventilated with a mixture of room air and 100% oxygen (respiratory rate, 65-70 breaths/min). After a thoracotomy in the fourth intercostal space, the heart was exposed and a thread was passed around the left anterior descending coronary artery (LAD) to occlude it. After 3 weeks of reperfusion, LV pressure (LVP) was measured by a 2F catheter-tip micromanometer (Model SPC-320, Millar Instruments, USA) inserted via the right carotid artery. The peak of the first derivative of LVP (+dP/dt) and the time constant of isovolumetric LVP decay (Tau) were calculated by an online data acquisition system (CODAS, DATAQ Instruments, Achron, OH, USA). The body temparature was maintained at 37±0.3°C by a heating pad. ReagentsDiazoxide (Funakoshi, Osaka, Japan) was dissolved in dimethylsulfoxide (DMSO), the final concentration of which was less than 0.1%. Nicorandil (Chugai, Tokyo, Japan) was dissolved in saline at a concentration of 1.0 J 2002; 66: 411 -415 (Received October 26, 2001; revised manuscript received December ...

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Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

Cited by 25 publications

References 39 publications

Involvement of Guanylate Cyclase and K+ Channels in Relaxation Evoked by Ferulate Nitrate in Rat Aorta Artery

Involvement of Guanylate Cyclase and K+ Channels in Relaxation Evoked by Ferulate Nitrate in Rat Aorta Artery

Visceral Periadventitial Adipose Tissue Regulates Arterial Tone of Mesenteric Arteries

Effect of Ischemic Preconditioning and Mitochondrial KATP Channel Openers on Chronic Left Ventricular Remodeling in the Ischemic-Reperfused Rat Heart.

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