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Comparison of hCRF and oCRF effects on cardiovascular responses after central, peripheral, and in vitro application
1Institute of Molecular Pharmacology, Berlin, Germany.
Insights
Human corticotropin-releasing factor (hCRF) and ovine CRF (oCRF) impact cardiovascular responses differently. These neuropeptides show distinct effects on blood pressure and heart rate, with hCRF generally being more potent.
Area of Science:
- Cardiovascular Physiology
- Neuroendocrinology
- Pharmacology
Background:
- Neuropeptides like corticotropin-releasing factor (CRF) play roles in stress response and physiological regulation.
- Understanding the cardiovascular effects of different CRF analogues is crucial for elucidating their biological functions.
Purpose of the Study:
- To investigate and compare the cardiovascular effects of human corticotropin-releasing factor (hCRF) and ovine corticotropin-releasing factor (oCRF).
- To determine the dose-dependent responses and identify structural differences influencing biological activity.
Main Methods:
- Administered hCRF and oCRF intracerebroventricularly (ICV) and intravenously (IV) in conscious rats.
- Conducted in vitro experiments using isometric ring preparations of mesenteric resistance arteries.
- Utilized a CRF analogue, alpha-helical CRF(9-41), to inhibit peptide effects.
Main Results:
- Central hCRF and oCRF administration (ICV) dose-dependently increased blood pressure and heart rate.
- Peripheral administration (IV) of hCRF and oCRF dose-dependently decreased blood pressure and caused tachycardia.
- Both peptides induced relaxation in mesenteric resistance arteries in vitro, with hCRF showing a more pronounced effect.
- Alpha-helical CRF(9-41) inhibited all observed cardiovascular effects, most potently against oCRF.
Conclusions:
- Structural differences between hCRF and oCRF lead to distinct cardiovascular activities.
- Both central and peripheral administration of these neuropeptides elicit significant, albeit different, physiological responses.
- CRF analogues exhibit potent inhibitory effects on CRF-mediated cardiovascular actions.
Abstract:
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 micrograms, ICV) caused an increase in blood pressure and heart rate, whereas peripheral administration (0.75-750 micrograms/kg, IV) produced a decrease in blood pressure and tachycardia. Isometric ring preparations of mesenteric resistance arteries (diameter 200 microns) relaxed in response to both peptides (1-100 nM). In all cases, the effects were more pronounced for hCRF compared to 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.