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Article: Effects of the converting enzyme inhibitor cilazaprilat on endothelium-dependent responses

TitleEffects of the converting enzyme inhibitor cilazaprilat on endothelium-dependent responses
Authors
Issue Date1991
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/
Citation
Hypertension, 1991, v. 18 n. 4 SUPPL., p. II22-II29 How to Cite?
AbstractThe effects of cilazaprilat were assessed on endothelium-dependent relaxations and contractions in isolated canine arteries. In coronary arteries incubated with indomethacin, cilazaprilat potentiated endothelium-dependent relaxations to bradykinin. In superfusion-perfusion bioassay studies with femoral arteries, cilazaprilat augmented the release of nonprostanoid endothelium-derived relaxing factors caused by bradykinin. To verify whether this effect was solely due to inhibition of the converting enzyme, the effects of cilazaprilat on responses to a variety of endothelium-dependent vasoactive agents were assessed. Endothelium-dependent relaxations to acetylcholine, thrombin, and vasopressin were not altered significantly by cilazaprilat. However, those induced by ADP and aggregating platelets were enhanced significantly by the compound. Endothelium-dependent relaxations to ADP-β-S were augmented significantly but to a lesser extent. Furthermore, in the presence of the nitric oxide synthase antagonist N(G)-nitro-L-arginine, ADP-β-S still caused small relaxations that were possibly mediated by endothelium-derived hyperpolarizing factor. These relaxations were augmented by cilazaprilat. Thus, the augmentation of purinergic relaxations may involve an increased production of endothelium-derived relaxing factors in addition to the protection of ADP from breakdown. Cilazaprilat did not affect endothelium-dependent contractions to acetylcholine or the calcium ionophore A23187 in canine basilar arteries, previously shown to be mediated by superoxide anions. Thus, cilazaprilat is not a scavenger of superoxide anion. Because this agent potentiates endothelium-dependent relaxations to bradykinin, ADP, and aggregating platelets, the present study suggests that, in addition to the lowering of plasmatic levels of angiotensin II, the antihypertensive and cardioprotective effects of cilazaprilat are mediated through an increased production of endothelium-derived relaxing factors.
Persistent Identifierhttp://hdl.handle.net/10722/171026
ISSN
2015 Impact Factor: 6.294
2015 SCImago Journal Rankings: 3.702

 

DC FieldValueLanguage
dc.contributor.authorMombouli, JVen_US
dc.contributor.authorNephtali, Men_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:11:53Z-
dc.date.available2012-10-30T06:11:53Z-
dc.date.issued1991en_US
dc.identifier.citationHypertension, 1991, v. 18 n. 4 SUPPL., p. II22-II29en_US
dc.identifier.issn0194-911Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/171026-
dc.description.abstractThe effects of cilazaprilat were assessed on endothelium-dependent relaxations and contractions in isolated canine arteries. In coronary arteries incubated with indomethacin, cilazaprilat potentiated endothelium-dependent relaxations to bradykinin. In superfusion-perfusion bioassay studies with femoral arteries, cilazaprilat augmented the release of nonprostanoid endothelium-derived relaxing factors caused by bradykinin. To verify whether this effect was solely due to inhibition of the converting enzyme, the effects of cilazaprilat on responses to a variety of endothelium-dependent vasoactive agents were assessed. Endothelium-dependent relaxations to acetylcholine, thrombin, and vasopressin were not altered significantly by cilazaprilat. However, those induced by ADP and aggregating platelets were enhanced significantly by the compound. Endothelium-dependent relaxations to ADP-β-S were augmented significantly but to a lesser extent. Furthermore, in the presence of the nitric oxide synthase antagonist N(G)-nitro-L-arginine, ADP-β-S still caused small relaxations that were possibly mediated by endothelium-derived hyperpolarizing factor. These relaxations were augmented by cilazaprilat. Thus, the augmentation of purinergic relaxations may involve an increased production of endothelium-derived relaxing factors in addition to the protection of ADP from breakdown. Cilazaprilat did not affect endothelium-dependent contractions to acetylcholine or the calcium ionophore A23187 in canine basilar arteries, previously shown to be mediated by superoxide anions. Thus, cilazaprilat is not a scavenger of superoxide anion. Because this agent potentiates endothelium-dependent relaxations to bradykinin, ADP, and aggregating platelets, the present study suggests that, in addition to the lowering of plasmatic levels of angiotensin II, the antihypertensive and cardioprotective effects of cilazaprilat are mediated through an increased production of endothelium-derived relaxing factors.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/en_US
dc.relation.ispartofHypertensionen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAdenosine Diphosphate - Pharmacologyen_US
dc.subject.meshAngiotensin-Converting Enzyme Inhibitors - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBradykinin - Pharmacologyen_US
dc.subject.meshCilazapril - Analogs & Derivativesen_US
dc.subject.meshCoronary Vessels - Drug Effects - Physiologyen_US
dc.subject.meshDogsen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Physiologyen_US
dc.subject.meshNitric Oxide - Secretionen_US
dc.subject.meshPyridazines - Pharmacologyen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.subject.meshVasodilation - Drug Effectsen_US
dc.titleEffects of the converting enzyme inhibitor cilazaprilat on endothelium-dependent responsesen_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.pmid1916998-
dc.identifier.scopuseid_2-s2.0-0026045866en_US
dc.identifier.volume18en_US
dc.identifier.issue4 SUPPL.en_US
dc.identifier.spageII22en_US
dc.identifier.epageII29en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMombouli, JV=7004285772en_US
dc.identifier.scopusauthoridNephtali, M=6507707101en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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