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.