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Article: Inhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation

TitleInhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation
Authors
Issue Date2003
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/healun
Citation
Journal Of Heart And Lung Transplantation, 2003, v. 22 n. 4, p. 439-451 How to Cite?
AbstractBackground: The endothelium protects the vascular wall through the nitric oxide (NO) release. Coronary endothelial dysfunction occurs early after heart transplantation and predicts the development of intimal thickening typical of graft coronary vasculopathy. Objective: We designed this study to examine the effect of endothelial NO synthase (eNOS) inhibition on the endothelial dysfunction caused by rejection and on the development of accelerated atherosclerosis after heart transplantation. Methods: To study the effect on these 2 end-points of inhibiting eNOS with intracoronary L-nitro arginine methyl ester (L-NAME; 1 mg/kg/day), infused with an osmotic pump for 30 days, we used a porcine model of heterotopic heart transplantation with pre-operative immunologic typing, to permit slow rejection without the need for immunosuppression. The endothelium-dependent relaxations of allografted coronary arteries, allografted arteries infused with L-NAME, allografted arteries mounted with the pump, and vehicle and native coronary arteries were compared 30 days after graft implantation using standard organ chamber experiments. We evaluated intimal thickening using a semi-quantitative scale (0-4+ grading). Results: A significant decrease in relaxations to serotonin (5-HT) occurred in allografted arteries infused directly with L-NAME compared with allografted arteries from swine receiving 5-HT, and relaxations in the latter were decreased compared with those of swine receiving the vehicle and native coronary arteries (p < 0.05). We found no significant differences in endothelium-dependent relaxations to bradykinin among coronary rings from all groups. We observed a significant increase in the prevalence and severity of intimal thickening in allografted coronary arteries infused with L-NAME compared with allografts not infused (p < 0.05), which had significantly more intimal thickening compared with native coronary arteries (p < 0.05). Conclusion: These results demonstrate that inhibiting the NO pathway worsens the endothelial dysfunction caused by rejection after heart transplantation and accelerates the intimal thickening process, leading to graft coronary vasculopathy. Strategies designed to preserve endothelial integrity and function of the endothelial NO pathway should be used to prevent graft coronary vasculopathy.
Persistent Identifierhttp://hdl.handle.net/10722/171291
ISSN
2015 Impact Factor: 7.509
2015 SCImago Journal Rankings: 3.655
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPerrault, LPen_US
dc.contributor.authorMalo, Oen_US
dc.contributor.authorBidouard, JPen_US
dc.contributor.authorVilleneuve, Nen_US
dc.contributor.authorVilaine, JPen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:13:13Z-
dc.date.available2012-10-30T06:13:13Z-
dc.date.issued2003en_US
dc.identifier.citationJournal Of Heart And Lung Transplantation, 2003, v. 22 n. 4, p. 439-451en_US
dc.identifier.issn1053-2498en_US
dc.identifier.urihttp://hdl.handle.net/10722/171291-
dc.description.abstractBackground: The endothelium protects the vascular wall through the nitric oxide (NO) release. Coronary endothelial dysfunction occurs early after heart transplantation and predicts the development of intimal thickening typical of graft coronary vasculopathy. Objective: We designed this study to examine the effect of endothelial NO synthase (eNOS) inhibition on the endothelial dysfunction caused by rejection and on the development of accelerated atherosclerosis after heart transplantation. Methods: To study the effect on these 2 end-points of inhibiting eNOS with intracoronary L-nitro arginine methyl ester (L-NAME; 1 mg/kg/day), infused with an osmotic pump for 30 days, we used a porcine model of heterotopic heart transplantation with pre-operative immunologic typing, to permit slow rejection without the need for immunosuppression. The endothelium-dependent relaxations of allografted coronary arteries, allografted arteries infused with L-NAME, allografted arteries mounted with the pump, and vehicle and native coronary arteries were compared 30 days after graft implantation using standard organ chamber experiments. We evaluated intimal thickening using a semi-quantitative scale (0-4+ grading). Results: A significant decrease in relaxations to serotonin (5-HT) occurred in allografted arteries infused directly with L-NAME compared with allografted arteries from swine receiving 5-HT, and relaxations in the latter were decreased compared with those of swine receiving the vehicle and native coronary arteries (p < 0.05). We found no significant differences in endothelium-dependent relaxations to bradykinin among coronary rings from all groups. We observed a significant increase in the prevalence and severity of intimal thickening in allografted coronary arteries infused with L-NAME compared with allografts not infused (p < 0.05), which had significantly more intimal thickening compared with native coronary arteries (p < 0.05). Conclusion: These results demonstrate that inhibiting the NO pathway worsens the endothelial dysfunction caused by rejection after heart transplantation and accelerates the intimal thickening process, leading to graft coronary vasculopathy. Strategies designed to preserve endothelial integrity and function of the endothelial NO pathway should be used to prevent graft coronary vasculopathy.en_US
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/healunen_US
dc.relation.ispartofJournal of Heart and Lung Transplantationen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCoronary Artery Disease - Etiology - Pathology - Physiopathologyen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Pathology - Physiopathologyen_US
dc.subject.meshEnzyme Inhibitors - Administration & Dosage - Therapeutic Useen_US
dc.subject.meshFemaleen_US
dc.subject.meshGraft Rejection - Etiology - Pathology - Physiopathologyen_US
dc.subject.meshHeart Transplantation - Adverse Effectsen_US
dc.subject.meshHyperplasia - Etiology - Pathology - Physiopathologyen_US
dc.subject.meshInfusions, Parenteralen_US
dc.subject.meshMaleen_US
dc.subject.meshNg-Nitroarginine Methyl Ester - Administration & Dosage - Therapeutic Useen_US
dc.subject.meshNitric Oxide Synthase - Antagonists & Inhibitorsen_US
dc.subject.meshSeverity Of Illness Indexen_US
dc.subject.meshSignal Transduction - Drug Effectsen_US
dc.subject.meshSwineen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTunica Intima - Drug Effects - Pathology - Physiopathologyen_US
dc.titleInhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantationen_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.doi10.1016/S1053-2498(02)00494-1en_US
dc.identifier.pmid12681422-
dc.identifier.scopuseid_2-s2.0-0037381109en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037381109&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume22en_US
dc.identifier.issue4en_US
dc.identifier.spage439en_US
dc.identifier.epage451en_US
dc.identifier.isiWOS:000182020300009-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPerrault, LP=7004370552en_US
dc.identifier.scopusauthoridMalo, O=6602767845en_US
dc.identifier.scopusauthoridBidouard, JP=6601955808en_US
dc.identifier.scopusauthoridVilleneuve, N=7003458215en_US
dc.identifier.scopusauthoridVilaine, JP=7004617134en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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