Coronary vasodilation and positive inotropism by urocortin in the isolatedrat heart

Corticotropin-releasing factor (CRF) has a coronary vasodilator effect and a positive inotropic effect on the isolated rat heart. Recently, expression of CRF receptor type 2 (CRF-R2) has been demonstrated in the heart. In add ition, urocortin (Ucn), a new member of the CRF family, has been reported t o have much greater affinity for CRF-R2 than CRF. It is suggested that the cardiac effects of Ucn may be more potent than those of CRF. We compared the effect of Ucn with that: of CRF on isolated rat heart. The effects of Ucn were then analyzed to determine whether these effects were m ediated by CRF receptors and/or any other mediators under the following con ditions: perfusion buffer containing (1) a-helical CRF 9-41, (2) indomethac in, (3) N-G-nitro-L-arginine methylester and (4) propranolol. Ucn exhibited a greater effect with a longer duration of action than CRF. Indomethacin s ignificantly attenuated the vasodilator effects of Ucn (P < 0.05). CRF rece ptor antagonist diminished both coronary vasodilation and the positive inot ropic effects of Ucn (P < 0.05). These results suggest that the cardiac effects of Ucn may be mediated by a CRF receptor, and prostaglandins may be involved in the vasodilator effect.