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Article: Effects of the Ca2+ antagonist RO 40-5967 on endothelium-dependent responses of isolated arteries

TitleEffects of the Ca2+ antagonist RO 40-5967 on endothelium-dependent responses of isolated arteries
Authors
Issue Date1994
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/
Citation
Journal Of Cardiovascular Pharmacology, 1994, v. 23 n. 6, p. 869-876 How to Cite?
AbstractExperiments were designed to determine whether the Ca2+ channel inhibitor RO 40-5967 [(1S,2S)-2-[2-[[3-(2- benzimidazolyl)propyl]methylamine]ethyl]-6-fluoro-1,2,3,4-tetr ahydro-1- isopropyl-2-naphthyl methoxyacetate dihydrochloride] causes endothelium- dependent relaxations or inhibits endothelium-dependent contractions of isolated blood vessels. Rings of dog femoral, carotid, and basilar arteries and of rat aorta, with and without endothelium, were suspended in conventional organ chambers for measurement of isometric force. During contractions evoked by phenylephrine (full α1-adrenergic agonist), St 587 (partial α1-adrenergic agonist) and endothelin-1 (ET), RO 40-5967 caused concentration-dependent relaxations of rings of dog femoral arteries; the relaxations to RO 40-5967 were greater in rings with endothelium than in those without endothelium. Nitro-L-arginine (NLA) and methylene blue (MB) inhibited the endothelium-dependent component of the response to RO 40-5967 during contractions to phenylephrine (PE) St 587 and ET. The endothelium- dependent relaxations evoked by RO 40-5967 during contractions to PE were not affected by diltiazem in the femoral artery, suggesting that this effect of the compound may not be related to its calcium channel inhibitor properties. Under bioassay conditions, RO 40-5967 stimulated release of relaxing factors from the endothelium of canine carotid arteries; the response of the detector tissues was inhibited by MB. In strips of canine femoral artery with endothelium, in which membrane potential of vascular smooth muscle cells (VSMC) was recorded with glass microelectrodes, RO 40-5967 did not cause endothelium-dependent hyperpolarizations. RO 40-5967 caused concentration- dependent inhibition of endothelium-dependent contractions of canine basilar arteries to acetylcholine (ACh), arachidonic acid (AA), and the Ca2+ ionophore A23187. Likewise, RO 40-5967 decreased the contractions evoked by ACh in rings with endothelium of the aorta of spontaneously hypertensive rats. These experiments suggest that in isolated arteries RO 40-5967 causes release of endothelium-derived relaxing factor (EDRF; nitric oxide, NO) and inhibits endothelium-dependent contractions. These effects of the compound may help explain its vasodilator properties in vivo.
Persistent Identifierhttp://hdl.handle.net/10722/171133
ISSN
2015 Impact Factor: 2.462
2015 SCImago Journal Rankings: 0.962
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBoulanger, CMen_US
dc.contributor.authorNakashima, Men_US
dc.contributor.authorOlmos, Len_US
dc.contributor.authorJoly, Gen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:12:20Z-
dc.date.available2012-10-30T06:12:20Z-
dc.date.issued1994en_US
dc.identifier.citationJournal Of Cardiovascular Pharmacology, 1994, v. 23 n. 6, p. 869-876en_US
dc.identifier.issn0160-2446en_US
dc.identifier.urihttp://hdl.handle.net/10722/171133-
dc.description.abstractExperiments were designed to determine whether the Ca2+ channel inhibitor RO 40-5967 [(1S,2S)-2-[2-[[3-(2- benzimidazolyl)propyl]methylamine]ethyl]-6-fluoro-1,2,3,4-tetr ahydro-1- isopropyl-2-naphthyl methoxyacetate dihydrochloride] causes endothelium- dependent relaxations or inhibits endothelium-dependent contractions of isolated blood vessels. Rings of dog femoral, carotid, and basilar arteries and of rat aorta, with and without endothelium, were suspended in conventional organ chambers for measurement of isometric force. During contractions evoked by phenylephrine (full α1-adrenergic agonist), St 587 (partial α1-adrenergic agonist) and endothelin-1 (ET), RO 40-5967 caused concentration-dependent relaxations of rings of dog femoral arteries; the relaxations to RO 40-5967 were greater in rings with endothelium than in those without endothelium. Nitro-L-arginine (NLA) and methylene blue (MB) inhibited the endothelium-dependent component of the response to RO 40-5967 during contractions to phenylephrine (PE) St 587 and ET. The endothelium- dependent relaxations evoked by RO 40-5967 during contractions to PE were not affected by diltiazem in the femoral artery, suggesting that this effect of the compound may not be related to its calcium channel inhibitor properties. Under bioassay conditions, RO 40-5967 stimulated release of relaxing factors from the endothelium of canine carotid arteries; the response of the detector tissues was inhibited by MB. In strips of canine femoral artery with endothelium, in which membrane potential of vascular smooth muscle cells (VSMC) was recorded with glass microelectrodes, RO 40-5967 did not cause endothelium-dependent hyperpolarizations. RO 40-5967 caused concentration- dependent inhibition of endothelium-dependent contractions of canine basilar arteries to acetylcholine (ACh), arachidonic acid (AA), and the Ca2+ ionophore A23187. Likewise, RO 40-5967 decreased the contractions evoked by ACh in rings with endothelium of the aorta of spontaneously hypertensive rats. These experiments suggest that in isolated arteries RO 40-5967 causes release of endothelium-derived relaxing factor (EDRF; nitric oxide, NO) and inhibits endothelium-dependent contractions. These effects of the compound may help explain its vasodilator properties in vivo.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/en_US
dc.relation.ispartofJournal of Cardiovascular Pharmacologyen_US
dc.subject.meshAdrenergic Alpha-Agonists - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta - Drug Effects - Physiologyen_US
dc.subject.meshArteries - Drug Effects - Physiologyen_US
dc.subject.meshBasilar Artery - Drug Effects - Physiologyen_US
dc.subject.meshBenzimidazoles - Pharmacologyen_US
dc.subject.meshCalcium Channel Blockers - Pharmacologyen_US
dc.subject.meshDogsen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshEndothelins - Pharmacologyen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Physiology - Secretionen_US
dc.subject.meshMembrane Potentials - Drug Effects - Physiologyen_US
dc.subject.meshMibefradilen_US
dc.subject.meshMuscle Contraction - Drug Effectsen_US
dc.subject.meshMuscle, Smooth, Vascular - Drug Effects - Physiology - Secretionen_US
dc.subject.meshNitric Oxide - Secretionen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Shren_US
dc.subject.meshReceptors, Adrenergic, Alpha-1 - Physiologyen_US
dc.subject.meshTetrahydronaphthalenes - Pharmacologyen_US
dc.titleEffects of the Ca2+ antagonist RO 40-5967 on endothelium-dependent responses of isolated arteriesen_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/00005344-199406000-00003-
dc.identifier.pmid7523777-
dc.identifier.scopuseid_2-s2.0-0028182896en_US
dc.identifier.volume23en_US
dc.identifier.issue6en_US
dc.identifier.spage869en_US
dc.identifier.epage876en_US
dc.identifier.isiWOS:A1994NP56100003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBoulanger, CM=7006599024en_US
dc.identifier.scopusauthoridNakashima, M=35599797500en_US
dc.identifier.scopusauthoridOlmos, L=7005286818en_US
dc.identifier.scopusauthoridJoly, G=7005110329en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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