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

We investigated effects of bolus administration of corticotropin-relea sing factor (CRF) on parameters of cardiac activity in isolated workin g rat hearts. Effects at a dose of 5 mug of CRF were compared in heart s 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 prolo nged vasodilatory action of the peptide. CRF, in addition, induced tra nsient (lasting <10 min) increases in maximum aortic pressure and oxyg en consumption (P < 0.01), suggesting an inotropic action of the pepti de. Perfusions of NE and propranolol did not change the cardiac respon se to CRF. L-NNA, inhibiting release of endothelium-derived relaxant f actor (EDRF), and indomethacin diminished the vasodilatory response to CRF, as indicated by significantly shortened increases in coronary fl ow 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 mediati on of coronary vasodilation by CRF involves the endothelial release of prostacyclin and EDRF.