EFFECTS OF CORTICOTROPIN-RELEASING FACTOR ON ISOLATED RAT-HEART ACTIVITY

We investigated effects of bolus administration of corticotropin-releasing factor (CRF) on parameters of cardiac activity in isolated working rat hearts. Effects at a dose of 5 mug of CRF were compared in hearts perfused with Krebs-Henseleit solution, norepinephrine (NE, 10(-9) M), propranolol (3 x 10(-6) M), N(G)-nitro-L-arginine (L-NNA, 3 x 10(-5) M), or indomethacin (3 x 10(-5) M). CRF increased coronary flow for >30 min (P < 0.01) with maximum increases of 31.7%, suggesting a prolonged vasodilatory action of the peptide. CRF, in addition, induced transient (lasting <10 min) increases in maximum aortic pressure and oxygen consumption (P < 0.01), suggesting an inotropic action of the peptide. Perfusions of NE and propranolol did not change the cardiac response to CRF. L-NNA, inhibiting release of endothelium-derived relaxant factor (EDRF), and indomethacin diminished the vasodilatory response to CRF, as indicated by significantly shortened increases in coronary flow after CRF (P < 0.05). Indomethacin also enhanced peak increases in maximum aortic pressure after CRF (P < 0.01). The data confirm direct effects of CRF on cardiac activity. They also suggest that the mediation of coronary vasodilation by CRF involves the endothelial release of prostacyclin and EDRF.