RGD Reference Report - Urotensin II and urotensin II-related peptide (URP) in cardiac ischemia-reperfusion injury. - Rat Genome Database

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Urotensin II and urotensin II-related peptide (URP) in cardiac ischemia-reperfusion injury.

Authors: Prosser, HC  Forster, ME  Richards, AM  Pemberton, CJ 
Citation: Prosser HC, etal., Peptides. 2008 May;29(5):770-7. Epub 2007 Aug 21.
RGD ID: 2306836
Pubmed: PMID:17900760   (View Abstract at PubMed)
DOI: DOI:10.1016/j.peptides.2007.08.013   (Journal Full-text)

Circulating urotensin II (UII) concentrations and the tissue expression of its cognate receptor (UT) are elevated in patients with cardiovascular disease (CVD). The functional significance of elevated plasma UII levels in CVD is unclear. Urotensin-related peptide (URP) is a paralog of UII in that it contains the six amino acid ring structures found in UII. Although both peptides are implicated as bioactive factors capable of modulating cardiovascular status, the role of both UII and URP in ischemic injury is unknown. Accordingly, we provide here the first report describing the direct cardiac effects of UII and URP in ischemia-reperfusion injury. Isolated perfused rat hearts were subjected to no-flow global ischemia for 45 min after 30min preconditioning with either 1nM rUII or 10nM URP. Both rUII- and URP-induced significant vasodilation of coronary arteries before (both P<0.05) and after ischemia (both P<0.05). Rat UII alone lowered contractility prior to ischemia (P=0.053). Specific assay of perfusate revealed rUII and URP both significantly inhibited reperfusion myocardial creatine kinase (CK) release (P=0.012 and 0.036, respectively) and atrial natriuretic peptide (ANP) secretion (P=0.025). Antagonism of the UT receptor with 1muM palosuran caused a significant increase in perfusion pressure (PP) prior to and post-ischemia. Furthermore, palosuran significantly inhibited reductions in both PP and myocardial damage marker release induced by both rUII and URP. In conclusion, our data suggests rUII and URP reduce cardiac ischemia-reperfusion injury by increasing flow through the coronary circulation, reducing contractility and therefore myocardial energy demand, and inhibiting reperfusion myocardial damage. Thus, UII and URP present as novel peptides with potential cardioprotective actions.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Uts2rRatpositive regulation of blood pressure  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Uts2  (urotensin 2)
Uts2r  (urotensin 2 receptor)

Genes (Mus musculus)
Uts2  (urotensin 2)
Uts2r  (urotensin 2 receptor)

Genes (Homo sapiens)
UTS2  (urotensin 2)
UTS2R  (urotensin 2 receptor)


Additional Information