Corticotropin-releasing hormone-receptor 2 is required for acute stress-induced bladder vascular permeability and release of vascular endothelial growth factor
| Autor: | Margaret Michaelian, Duraisamy Kempuraj, Theoharis C. Theoharides, William Boucher |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
endocrine system
medicine.medical_specialty Urinary bladder business.industry Urology Urinary system Interstitial cystitis Vascular permeability medicine.disease Vascular endothelial growth factor chemistry.chemical_compound medicine.anatomical_structure Endocrinology nervous system chemistry Internal medicine polycyclic compounds medicine Antalarmin business hormones hormone substitutes and hormone antagonists medicine.drug Evans Blue Blood vessel |
| Zdroj: | BJU International. 106:1394-1399 |
| ISSN: | 1464-4096 |
| DOI: | 10.1111/j.1464-410x.2010.09237.x |
| Popis: | 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 mm2 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. |
| Databáze: | OpenAIRE |
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