Abstract:
BACKGROUND:Corticotropin-releasing factor (CRF) peptides exert profound effects on the secretomotor function of the gastrointestinal tract. Nevertheless, despite the presence of CRF peptides and receptors in colonic tissue, their influence on colonic blood flow (CBF) is unknown. AIM:To determine the effect and mechanism of members of the CRF peptide family on CBF in isoflurane-anesthetized rats. METHODS:Proximal CBF was measured with laser-Doppler flowmetry simultaneously with mean arterial blood pressure (MABP) measurement. Rats were injected with intravenous human/rat CRF (CRF1 > CRF2 affinity), mouse urocortin 2 (mUcn2, selective CRF2 agonist), or sauvagine (SVG, CRF2 > CRF1 affinity) at 1-30 µg/kg. The nitric oxide (NO) synthase inhibitor, L-NAME (3 mg/kg, iv), the cyclooxygenase inhibitor, indomethacin (Indo, 5 mg/kg, ip), or selective CRF2 antagonist, astressin2-B (Ast2B, 50 µg/kg, iv) was given before SVG injection (10 µg/kg, iv). RESULTS:SVG and mUcn2 dose-dependently increased CBF while decreasing MABP and colonic vascular resistance (CVR). CRF had no effect on CBF, but increased CVR. The hyperemic effect of SVG was inhibited by L-NAME but not by Indo, whereas hypotension was partially reduced by L-NAME. Sensory denervation had no effect on SVG-induced changes. Ast2B inhibited SVG-induced hyperemia and decreased CVR, and partially reduced the hypotension. CONCLUSIONS:Peripheral CRF2 activation induces colonic hyperemia through NO synthesis, without involving prostaglandin synthesis or sensory nerve activation, suggesting a direct action on the endothelium and myenteric neurons. Members of the CRF peptide family may protect the colonic mucosa via the activation of the CRF2 receptor.
journal_name
Dig Dis Scijournal_title
Digestive diseases and sciencesauthors
Akiba Y,Kaunitz JD,Million Mdoi
10.1007/s10620-015-3579-ysubject
Has Abstractpub_date
2015-04-01 00:00:00pages
858-67issue
4eissn
0163-2116issn
1573-2568journal_volume
60pub_type
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