Int Neurourol J.
2022 Dec;26(4):299-307. 10.5213/inj.2244118.059.
Stress-Induced Changes in Trophic Factor Expression in the Rodent Urinary Bladder: Possible Links With Angiogenesis
- Rijk MMd
1,2 - Wolf-Johnston A3
- Kullmann AF3
- Maringer K4,5
- Sims-Lucas S4,5,6
- Koeveringe GAv1,2
- Rodríguez LV7
- Birder LA3,8
- Affiliations
-
- 1Department of Urology, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
- 2Department of Urology, Maastricht University Medical Center+ (MUMC+), Maastricht, The Netherlands
- 3Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- 4Rangos Research Center, Children’s Hospital of Pittsburgh of University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- 5Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- 6Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
- 7Department of Urology, Weill-Cornell Medical Center, New York, NY, USA
- 8Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- KMID: 2537306
- DOI: http://doi.org/10.5213/inj.2244118.059
Abstract
- Purpose
Substantive evidence supports a role of chronic stress in the development, maintenance, and even enhancement of functional bladder disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Increased urinary frequency and bladder hyperalgesia have been reported in rodents exposed to a chronic stress paradigm. Here, we utilized a water avoidance stress (WAS) model in rodents to investigate the effect of chronic stress on vascular perfusion and angiogenesis.
Methods
Female Wistar-Kyoto rats were exposed to WAS for 10 consecutive days. Bladder neck tissues were analyzed by western immunoblot for vascular endothelial growth factor (VEGF) and nerve growth factor precursor (proNGF). Vascular perfusion was assessed by fluorescent microangiography followed by Hypoxyprobe testing to identify regions of tissue hypoxia.
Results
The expression of VEGF and proNGF in the bladder neck mucosa was significantly higher in the WAS rats than in the controls. There was a trend toward increased vascular perfusion, but without a statistically significant difference from the control group. The WAS rats displayed a 1.6-fold increase in perfusion. Additionally, a greater abundance of vessels was observed in the WAS rats, most notably in the microvasculature.
Conclusions
These findings show that chronic psychological stress induces factors that can lead to increased microvasculature formation, especially around the bladder neck, the region that contains most nociceptive bladder afferents. These findings may indicate a link between angiogenesis and other inflammatory factors that contribute to structural changes and pain in IC/BPS.
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