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 micrograms of CRF were compared in hearts perfused with Krebs-Henseleit solution, norepinephrine (NE, 10(-9) M), propranolol (3 x 10(-6) M), NG-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.
Grunt
M
M
Department of Applied Physiology, University of Ulm, Germany.
Glaser
J
J
Schmidhuber
H
H
Pauschinger
P
P
Born
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; D011433:Propranolol; D009638:Norepinephrine; D007213:Indomethacin