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Article: Role of cyclooxygenase in ventricular effects of adrenomedullin: Is adrenomedullin a double-edged sword in sepsis?

TitleRole of cyclooxygenase in ventricular effects of adrenomedullin: Is adrenomedullin a double-edged sword in sepsis?
Authors
Issue Date2004
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal Of Physiology - Heart And Circulatory Physiology, 2004, v. 286 n. 3 55-3, p. H1034-H1042 How to Cite?
AbstractAdrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions. However, the direct inotropic effect of ADM on normal and compromised cardiomyocytes is not clear. In rat ventricular myocytes, ADM produced an initial (<30 min) increase in cell shortening and Ca 2+ transient and, on prolonged incubation (>1 h), a marked decrease in cell shortening and Ca2+ transient. Both effects were sensitive to inhibition by the ADM antagonist ADM-(22-52). The increase and decrease in cell shortening and Ca2+ transient were attenuated by pretreatment with indomethacin [a nonspecific cyclooxygenase (COX) inhibitor], nimesulide and SC-236 (specific COX-2 inhibitors), and tranylcypromine (a prostacyclin synthase inhibitor); SQ-29548 (a thromboxane receptor antagonist) was without effect. Cells isolated from LPS-treated rats that were in the late, hypodynamic phase of septic shock also showed a marked decrease in cell shortening and Ca2+ transient. Because ADM is overexpressed in sepsis, we repeated the above protocol in cells isolated from LPS-treated rats. At 4 h after LPS injection, ADM levels markedly increased in plasma, ventricles, and freshly isolated ventricular myocytes. Decreases in cell shortening and Ca2+ transient in LPS-treated cells were reversed by pretreatment with ADM-(22-52). Anti-ADM (rat) IgG also reversed the decrease in cell shortening and other parameters of cell kinetics. Indomethacin, SC-236, and tranylcypromine restored cell contractility and the decrease in Ca2+ transient, whereas SQ-29548 had no effect, implying that prostacyclin played a role in both effects. However, with regard to cell-shortening kinetics, indomethacin and SQ-29548 decreased the amount of time taken by the cells to return to baseline, whereas SC-236 and tranylcypromine did not, implying that not only prostacyclin, but also thromboxane, is involved. The results indicate that ADM interacts with COX to yield prostanoids, which mediate its negative inotropic effect in LPS-treated rat ventricular myocytes.
Persistent Identifierhttp://hdl.handle.net/10722/81147
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMittra, Sen_HK
dc.contributor.authorHyvelin, JMen_HK
dc.contributor.authorShan, Qen_HK
dc.contributor.authorTang, Fen_HK
dc.contributor.authorBourreau, JPen_HK
dc.date.accessioned2010-09-06T08:14:22Z-
dc.date.available2010-09-06T08:14:22Z-
dc.date.issued2004en_HK
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 2004, v. 286 n. 3 55-3, p. H1034-H1042en_HK
dc.identifier.issn0363-6135en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81147-
dc.description.abstractAdrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions. However, the direct inotropic effect of ADM on normal and compromised cardiomyocytes is not clear. In rat ventricular myocytes, ADM produced an initial (<30 min) increase in cell shortening and Ca 2+ transient and, on prolonged incubation (>1 h), a marked decrease in cell shortening and Ca2+ transient. Both effects were sensitive to inhibition by the ADM antagonist ADM-(22-52). The increase and decrease in cell shortening and Ca2+ transient were attenuated by pretreatment with indomethacin [a nonspecific cyclooxygenase (COX) inhibitor], nimesulide and SC-236 (specific COX-2 inhibitors), and tranylcypromine (a prostacyclin synthase inhibitor); SQ-29548 (a thromboxane receptor antagonist) was without effect. Cells isolated from LPS-treated rats that were in the late, hypodynamic phase of septic shock also showed a marked decrease in cell shortening and Ca2+ transient. Because ADM is overexpressed in sepsis, we repeated the above protocol in cells isolated from LPS-treated rats. At 4 h after LPS injection, ADM levels markedly increased in plasma, ventricles, and freshly isolated ventricular myocytes. Decreases in cell shortening and Ca2+ transient in LPS-treated cells were reversed by pretreatment with ADM-(22-52). Anti-ADM (rat) IgG also reversed the decrease in cell shortening and other parameters of cell kinetics. Indomethacin, SC-236, and tranylcypromine restored cell contractility and the decrease in Ca2+ transient, whereas SQ-29548 had no effect, implying that prostacyclin played a role in both effects. However, with regard to cell-shortening kinetics, indomethacin and SQ-29548 decreased the amount of time taken by the cells to return to baseline, whereas SC-236 and tranylcypromine did not, implying that not only prostacyclin, but also thromboxane, is involved. The results indicate that ADM interacts with COX to yield prostanoids, which mediate its negative inotropic effect in LPS-treated rat ventricular myocytes.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_HK
dc.subject.meshAdrenomedullinen_HK
dc.subject.meshAnesthesiaen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlood Pressureen_HK
dc.subject.meshCalcium Signaling - drug effects - physiologyen_HK
dc.subject.meshCyclooxygenase 1en_HK
dc.subject.meshCyclooxygenase 2en_HK
dc.subject.meshIsoenzymes - metabolismen_HK
dc.subject.meshLipopolysaccharides - pharmacologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMembrane Proteinsen_HK
dc.subject.meshMyocardial Contraction - drug effectsen_HK
dc.subject.meshMyocytes, Cardiac - metabolismen_HK
dc.subject.meshPeptide Fragments - pharmacologyen_HK
dc.subject.meshPeptides - metabolismen_HK
dc.subject.meshProstaglandin-Endoperoxide Synthases - metabolismen_HK
dc.subject.meshRadioimmunoassayen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.subject.meshSepsis - metabolismen_HK
dc.titleRole of cyclooxygenase in ventricular effects of adrenomedullin: Is adrenomedullin a double-edged sword in sepsis?en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9513&volume=286&spage=H1034&epage=H1042&date=2004&atitle=Role+of+cyclooxygenase+in+ventricular+effects+of+adrenomedullin:+is+adrenomedullin+a+double-edged+sword+in+sepsis?en_HK
dc.identifier.emailTang, F: ftang@hkucc.hku.hken_HK
dc.identifier.emailBourreau, JP: bourreau@hkucc.hku.hken_HK
dc.identifier.authorityTang, F=rp00327en_HK
dc.identifier.authorityBourreau, JP=rp00389en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpheart.00337.2003-
dc.identifier.pmid14766677-
dc.identifier.scopuseid_2-s2.0-1342325505en_HK
dc.identifier.hkuros92666en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1342325505&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue3 55-3en_HK
dc.identifier.spageH1034en_HK
dc.identifier.epageH1042en_HK
dc.identifier.isiWOS:000188783200030-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMittra, S=36725463300en_HK
dc.identifier.scopusauthoridHyvelin, JM=6602435488en_HK
dc.identifier.scopusauthoridShan, Q=7007145043en_HK
dc.identifier.scopusauthoridTang, F=7201979770en_HK
dc.identifier.scopusauthoridBourreau, JP=7003927886en_HK

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