COMPARISON OF HCRF AND OCRF EFFECTS ON CARDIOVASCULAR-RESPONSES AFTER CENTRAL, PERIPHERAL, AND IN-VITRO APPLICATION

Three assays have been used to show that the neuropeptides human corticotropin-releasing factor (hCRF) and the ovine analogue oCRF produced substantial dose-dependent cardiovascular responses. The assays included intracerebroventricular (ICV) and intravenous (IV) administration in conscious rats, and also in vitro experiments with resistance arteries. Central administration of the peptides (0.1-10 mu g, ICV) caused an increase in blood pressure and heart rate, whereas peripheral administration (0.75-750 mu g/kg, IV) produced a decrease in blood pressure and tachycardia. Isometric ring preparations of mesenteric resistance arteries (diameter 200 mu m) relaxed in response to both peptides (1-100 nM). In all cases, the effects were more pronounced for hCRF compared to oCRF. Furthermore, all effects were inhibited by the CRF analogue alpha-helical CRF(9-41), the effect of the analogue being most potent against oCRF. The results of all three assays indicate that the difference in structure between hCRF and oCRF produces differences in biological activity.