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Article: Modulation by simvastatin of iberiotoxin-sensitive, Ca 2+- activated K + channels of porcine coronary artery smooth muscle cells

TitleModulation by simvastatin of iberiotoxin-sensitive, Ca 2+- activated K + channels of porcine coronary artery smooth muscle cells
Authors
Issue Date2007
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2007, v. 151 n. 7, p. 987-997 How to Cite?
Abstract
Background and Purpose: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca 2+- activated K + (BK Ca) channels. Experimental Approaches: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK Ca channel gatings of porcine coronary artery smooth muscle cells were evaluated. Key Results: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 μM) (hydrophobic), but not simvastatin Na + (hydrophilic), inhibited the BK Ca channels with a minimal recovery upon washout. Isopimaric acid (10 μM)-mediated enhancement of the BK Ca amplitude was reversed by external simvastatin. Simvastatin Na + (10 μM, applied internally), markedly attenuated isopimaric acid (10 μM)-induced enhancement of the BK Ca amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 μM) and geranylgeranyl pyrophosphate (20 μM) only prevented simvastatin (1 and 3 μM)-induced responses. simvastatin (10 μM) caused a rottlerin (1 μM)-sensitive (cycloheximide (10 μM)-insensitive) increase of PKC-δ protein expression. Conclusions and Implications: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK Ca channels of the arterial smooth muscle cells through multiple intracellular pathways. © 2007 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/171357
ISSN
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
References

 

Author Affiliations
  1. The University of Hong Kong
  2. Union Hospital
  3. Prince of Wales Hospital Hong Kong
  4. University of Macau
  5. Hong Kong Polytechnic University
  6. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorSeto, SWen_US
dc.contributor.authorAu, ALSen_US
dc.contributor.authorLam, TYen_US
dc.contributor.authorChim, SSCen_US
dc.contributor.authorLee, SMYen_US
dc.contributor.authorWan, Sen_US
dc.contributor.authorTjiu, DCSen_US
dc.contributor.authorShigemura, Nen_US
dc.contributor.authorYim, APCen_US
dc.contributor.authorChan, SWen_US
dc.contributor.authorTsui, SKWen_US
dc.contributor.authorLeung, GPHen_US
dc.contributor.authorKwan, YWen_US
dc.date.accessioned2012-10-30T06:13:34Z-
dc.date.available2012-10-30T06:13:34Z-
dc.date.issued2007en_US
dc.identifier.citationBritish Journal Of Pharmacology, 2007, v. 151 n. 7, p. 987-997en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/171357-
dc.description.abstractBackground and Purpose: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca 2+- activated K + (BK Ca) channels. Experimental Approaches: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK Ca channel gatings of porcine coronary artery smooth muscle cells were evaluated. Key Results: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 μM) (hydrophobic), but not simvastatin Na + (hydrophilic), inhibited the BK Ca channels with a minimal recovery upon washout. Isopimaric acid (10 μM)-mediated enhancement of the BK Ca amplitude was reversed by external simvastatin. Simvastatin Na + (10 μM, applied internally), markedly attenuated isopimaric acid (10 μM)-induced enhancement of the BK Ca amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 μM) and geranylgeranyl pyrophosphate (20 μM) only prevented simvastatin (1 and 3 μM)-induced responses. simvastatin (10 μM) caused a rottlerin (1 μM)-sensitive (cycloheximide (10 μM)-insensitive) increase of PKC-δ protein expression. Conclusions and Implications: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK Ca channels of the arterial smooth muscle cells through multiple intracellular pathways. © 2007 Nature Publishing Group All rights reserved.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCaveolin 1 - Biosynthesisen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCoronary Vessels - Cytology - Drug Effects - Physiologyen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEnzyme Activation - Drug Effectsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshHydroxymethylglutaryl-Coa Reductase Inhibitors - Pharmacologyen_US
dc.subject.meshImidazoles - Pharmacologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Potentials - Drug Effectsen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMuscle, Smooth, Vascular - Cytology - Drug Effects - Physiologyen_US
dc.subject.meshMyocytes, Smooth Muscle - Drug Effects - Metabolism - Physiologyen_US
dc.subject.meshPeptides - Pharmacologyen_US
dc.subject.meshPhorbol Esters - Pharmacologyen_US
dc.subject.meshPotassium Channels, Calcium-Activated - Antagonists & Inhibitors - Metabolism - Physiologyen_US
dc.subject.meshProtein Kinase C-Delta - Metabolismen_US
dc.subject.meshPyridines - Pharmacologyen_US
dc.subject.meshSimvastatin - Chemistry - Pharmacologyen_US
dc.subject.meshSwineen_US
dc.titleModulation by simvastatin of iberiotoxin-sensitive, Ca 2+- activated K + channels of porcine coronary artery smooth muscle cellsen_US
dc.typeArticleen_US
dc.identifier.emailLeung, GPH:gphleung@hkucc.hku.hken_US
dc.identifier.authorityLeung, GPH=rp00234en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.bjp.0707327en_US
dc.identifier.pmid17558433en_US
dc.identifier.scopuseid_2-s2.0-34547602966en_US
dc.identifier.hkuros157508-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34547602966&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume151en_US
dc.identifier.issue7en_US
dc.identifier.spage987en_US
dc.identifier.epage997en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridSeto, SW=9941482400en_US
dc.identifier.scopusauthoridAu, ALS=7005391144en_US
dc.identifier.scopusauthoridLam, TY=18134321000en_US
dc.identifier.scopusauthoridChim, SSC=6701728226en_US
dc.identifier.scopusauthoridLee, SMY=35233892600en_US
dc.identifier.scopusauthoridWan, S=7202724268en_US
dc.identifier.scopusauthoridTjiu, DCS=18134494600en_US
dc.identifier.scopusauthoridShigemura, N=36966937200en_US
dc.identifier.scopusauthoridYim, APC=7102593653en_US
dc.identifier.scopusauthoridChan, SW=7404255670en_US
dc.identifier.scopusauthoridTsui, SKW=7004961364en_US
dc.identifier.scopusauthoridLeung, GPH=35963668200en_US
dc.identifier.scopusauthoridKwan, YW=7005662153en_US

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