Corticotropin-releasing hormone-receptor 2 is required for acute stress-induced bladder vascular permeability and release of vascular endothelial growth factor.

Abstract

OBJECTIVE:

To investigate the corticotropin-releasing hormone (CRH) receptor (CRH-R) requirement for the effect of acute stress on bladder vascular permeability and release of vascular endothelial growth factor (VEGF), as increasing evidence indicates that acute stress worsens certain inflammatory disorders, including interstitial cystitis/painful bladder syndrome (IC/PBlS), which is characterized by pain, variable bladder inflammation, increased expression of bladder vascular endothelial growth factor (VEGF), and many detrusor mast cells.

MATERIALS AND METHODS:

Bladders of normal C57BL/6, and C57BL/6- derived CRH-R1, CRH-R2 or double CRH-R1 + 2 knockout (-/-) female mice (10-12 weeks old) were catheterized under anaesthesia. After emptying the urine, normal saline was instilled with or without intravesical CRH-R antagonists in C57BL/6 mice before they were stressed by placing them in a restrainer for 30 min. Evans blue was injected in the tail vein before stress for the permeability experiments. The bladders from C57BL/6 or CRH-R -/- mice were then removed, minced into 1 mm(2) pieces and cultured overnight. Culture media were collected 24 h later for VEGF assay. C57BL/6 bladder was processed for CRH-R immunohistochemistry.

RESULTS:

Acute stress increased bladder vascular permeability in control C57BL/6 and CRH-R1 -/- mice, but not CRH-R2 -/- or CRH-R1+2 -/- mice. The CRH-R2 antagonist Astressin 2B, but not the CRH-R1 antagonist Antalarmin, inhibited stress-induced VEGF release from C57BL/6 mouse bladder explants. Stress could not induce a VEGF increase from bladder explants of CRH-R2 -/- or CRH-R1+2 -/- mice, but did so in CRH-R1 -/- mice. Bladder CRH-R2 immunoreactivity was detected in C57BL/6 bladders.

CONCLUSIONS:

Acute stress induces bladder vascular permeability and VEGF release that is dependent on CRH-R2. These findings suggest that CRH and VEGF might participate in the pathogenesis of IC/PBlS and provide for new therapeutic targets.

• Authors: William Boucher, Duraisamy Kempuraj, Margaret Michaelian, Theoharis C Theoharides
• Journal: BJU international (BJU Int) Vol. 106 Issue 9 Pg. 1394-9 (Nov 2010) ISSN: 1464-410X [Electronic] England
• PMID: 20201838 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

Chemical References

• CRF receptor type 2
• Receptors, Corticotropin-Releasing Hormone
• Vascular Endothelial Growth Factor A

Topics

• Acute Disease
• Animals
• Capillary Permeability (physiology)
• Cystitis, Interstitial (etiology, physiopathology)
• Female
• Immunohistochemistry
• Mast Cells (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Corticotropin-Releasing Hormone (metabolism)
• Stress, Psychological (complications, physiopathology)
• Vascular Endothelial Growth Factor A (metabolism)