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Article: Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors

TitlePotentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors
Authors
Issue Date1992
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 1992, v. 71 n. 1, p. 137-144 How to Cite?
AbstractStudies were designed to investigate the mechanisms underlying the augmentation by angiotensin I converting enzyme (ACE) inhibitors of the endothelium-dependent relaxations evoked by bradykinin. Isometric tension, tissue levels of cGMP, and transmembrane potential were measured in isolated canine coronary arteries as indications of the respective contribution of nitric oxide and endothelium-derived hyperpolarizing factor. In rings of coronary artery with endothelium, relaxations to bradykinin were potentiated by the ACE inhibitors cilazaprilat and perindoprilat. N(G)-Nitro-L-arginine (NLA), a nitric oxide synthase inhibitor, impaired relaxations to bradykinin. But the presence of ACE inhibitors partially restored this activity. Bradykinin stimulated the production of cGMP, and this was enhanced significantly by ACE inhibitors, indicating an augmented release of nitric oxide. NLA abolished the increase induced by bradykinin irrespective of the presence of ACE inhibitors. Electrophysiological studies revealed that bradykinin elicited an endothelium-dependent hyperpolarization of vascular smooth muscle that was insensitive to NLA and potentiated by ACE inhibitors. The bradykinin-induced hyperpolarization and NLA-resistant relaxations were transient and impaired by potassium depolarization. Thus, production of endothelium-derived hyperpolarizing factor may account for the NLA-resistant relaxations of canine coronary arteries. The relaxations induced by bradykinin were unaffected by the B1 kinin receptor antagonist des- Arg9,[Leu8]-bradykinin either in the absence or in the presence of NLA but were antagonized by the B2 kinin receptor antagonist D-Arg[Hyp3,D-Phe7]- bradykinin. Molecular exclusion chromatography of 125I-labeled [Tyr8]- bradykinin and its degradation products demonstrated that the breakdown of the kinin by isolated coronary arteries was prevented in the presence of perindoprilat. The experiments suggest that the potentiating effect of ACE inhibitors on relaxations evoked by bradykinin involves the protection of bradykinin from breakdown by ACE, which results in greater production of endothelium-derived nitric oxide and hyperpolarizing factor, via stimulation of endothelial B2 kinin receptors.
Persistent Identifierhttp://hdl.handle.net/10722/171066
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMombouli, JVen_US
dc.contributor.authorIlliano, Sen_US
dc.contributor.authorNagao, Ten_US
dc.contributor.authorScottBurden, Ten_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:12:03Z-
dc.date.available2012-10-30T06:12:03Z-
dc.date.issued1992en_US
dc.identifier.citationCirculation Research, 1992, v. 71 n. 1, p. 137-144en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/171066-
dc.description.abstractStudies were designed to investigate the mechanisms underlying the augmentation by angiotensin I converting enzyme (ACE) inhibitors of the endothelium-dependent relaxations evoked by bradykinin. Isometric tension, tissue levels of cGMP, and transmembrane potential were measured in isolated canine coronary arteries as indications of the respective contribution of nitric oxide and endothelium-derived hyperpolarizing factor. In rings of coronary artery with endothelium, relaxations to bradykinin were potentiated by the ACE inhibitors cilazaprilat and perindoprilat. N(G)-Nitro-L-arginine (NLA), a nitric oxide synthase inhibitor, impaired relaxations to bradykinin. But the presence of ACE inhibitors partially restored this activity. Bradykinin stimulated the production of cGMP, and this was enhanced significantly by ACE inhibitors, indicating an augmented release of nitric oxide. NLA abolished the increase induced by bradykinin irrespective of the presence of ACE inhibitors. Electrophysiological studies revealed that bradykinin elicited an endothelium-dependent hyperpolarization of vascular smooth muscle that was insensitive to NLA and potentiated by ACE inhibitors. The bradykinin-induced hyperpolarization and NLA-resistant relaxations were transient and impaired by potassium depolarization. Thus, production of endothelium-derived hyperpolarizing factor may account for the NLA-resistant relaxations of canine coronary arteries. The relaxations induced by bradykinin were unaffected by the B1 kinin receptor antagonist des- Arg9,[Leu8]-bradykinin either in the absence or in the presence of NLA but were antagonized by the B2 kinin receptor antagonist D-Arg[Hyp3,D-Phe7]- bradykinin. Molecular exclusion chromatography of 125I-labeled [Tyr8]- bradykinin and its degradation products demonstrated that the breakdown of the kinin by isolated coronary arteries was prevented in the presence of perindoprilat. The experiments suggest that the potentiating effect of ACE inhibitors on relaxations evoked by bradykinin involves the protection of bradykinin from breakdown by ACE, which results in greater production of endothelium-derived nitric oxide and hyperpolarizing factor, via stimulation of endothelial B2 kinin receptors.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.orgen_US
dc.relation.ispartofCirculation Researchen_US
dc.subject.meshAngiotensin I - Metabolismen_US
dc.subject.meshAngiotensin-Converting Enzyme Inhibitors - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshArteriesen_US
dc.subject.meshBradykinin - Metabolism - Pharmacologyen_US
dc.subject.meshCoronary Vessels - Drug Effects - Metabolismen_US
dc.subject.meshCyclic Gmp - Metabolismen_US
dc.subject.meshDogsen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshEndothelium, Vascular - Physiologyen_US
dc.subject.meshNitric Oxide - Physiologyen_US
dc.subject.meshVasodilationen_US
dc.titlePotentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factorsen_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.pmid1318793-
dc.identifier.scopuseid_2-s2.0-0026689477en_US
dc.identifier.volume71en_US
dc.identifier.issue1en_US
dc.identifier.spage137en_US
dc.identifier.epage144en_US
dc.identifier.isiWOS:A1992HZ76000017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMombouli, JV=7004285772en_US
dc.identifier.scopusauthoridIlliano, S=6602119848en_US
dc.identifier.scopusauthoridNagao, T=7401489430en_US
dc.identifier.scopusauthoridScottBurden, T=7004306459en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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