Ucn2 (
urocortin 2) is a recently discovered
peptide with therapeutic potential in
heart failure. As any new treatment is likely to be used in conjunction with standard ACEI (
angiotensin-converting enzyme inhibitor)
therapy, it is important that the combined effects of these agents are assessed. In the present study, we investigated the effects of Ucn2 and an ACEI (
captopril) administered for 3 h, both separately and together, in eight sheep with pacing-induced
heart failure. Ucn2 and
captopril alone both increased CO (cardiac output; Ucn2>
captopril) and decreased arterial pressure (
captopril>Ucn2), left atrial pressure (Ucn2>
captopril) and peripheral resistance (Ucn2=
captopril) relative to controls. Compared with either treatment alone, combined treatment further improved CO and reduced peripheral resistance and cardiac preload, without inducing further falls in blood pressure. In contrast with the marked increase in plasma
renin activity observed with
captopril alone, Ucn2 administration reduced
renin activity, whereas the combined agents resulted in intermediate
renin levels. All active treatments decreased circulating levels of
aldosterone (Ucn2+captopril>Ucn2=
captopril),
endothelin-1 and the
natriuretic peptides (Ucn2+captopril=Ucn2>
captopril), whereas
adrenaline (
epinephrine) fell only with Ucn2 (Ucn2+captopril=Ucn2), and
vasopressin increased during
captopril alone. Ucn2, both separately and in conjunction with
captopril, increased urine output,
sodium and
creatinine excretion and
creatinine clearance. Conversely,
captopril administered alone adversely affected these renal indices. In conclusion, co-treatment with Ucn2 and an ACEI in
heart failure produced significantly greater improvements in haemodynamics, hormonal profile and renal function than achieved by
captopril alone. These results indicate that dual treatment with these two agents is beneficial.