Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions

• Published in: PloS one Vol. 13; no. 3; p. e0193923
• Main Authors: McDonnell, Bronagh M, Buchanan, Paul J, Prise, Kevin M, McCloskey, Karen D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.03.2018; Public Library of Science (PLoS)
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Atropine - pharmacology; Biology and Life Sciences; Bladder; Calcium Signaling; Carbachol - pharmacology; Cystitis; Development and progression; Dose-Response Relationship, Radiation; Guinea Pigs; Health aspects; In Vitro Techniques; Male; Medical examination; Medicine and Health Sciences; Mucous Membrane - drug effects; Mucous Membrane - physiology; Muscle Contraction - drug effects; Muscle Contraction - radiation effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Muscle, Smooth - radiation effects; Physical Sciences; Radiation Dosage; Radiation exposure; Urinary Bladder - drug effects; Urinary Bladder - radiation effects
• DOI: 10.1371/journal.pone.0193923
• ISSN: 1932-6203

Radiation-induced bladder toxicity is associated with radiation therapy for pelvic malignancies, arising from unavoidable irradiation of neighbouring normal bladder tissue. This study aimed to investigate the acute impact of ionizing radiation on the contractility of bladder strips and identify the radiation-sensitivity of the mucosa vs the detrusor. Guinea-pig bladder strips (intact or mucosa-free) received ex vivo sham or 20Gy irradiation and were studied with in vitro myography, electrical field stimulation and Ca2+-fluorescence imaging. Frequency-dependent, neurogenic contractions in intact strips were reduced by irradiation across the force-frequency graph. The radiation-difference persisted in atropine (1μM); subsequent addition of PPADs (100μM) blocked the radiation effect at higher stimulation frequencies and decreased the force-frequency plot. Conversely, neurogenic contractions in mucosa-free strips were radiation-insensitive. Radiation did not affect agonist-evoked contractions (1μM carbachol, 5mM ATP) in intact or mucosa-free strips. Interestingly, agonist-evoked contractions were larger in irradiated mucosa-free strips vs irradiated intact strips suggesting that radiation may have unmasked an inhibitory mucosal element. Spontaneous activity was larger in control intact vs mucosa-free preparations; this difference was absent in irradiated strips. Spontaneous Ca2+-transients in smooth muscle cells within tissue preparations were reduced by radiation. Radiation affected neurogenic and agonist-evoked bladder contractions and also reduced Ca2+-signalling events in smooth muscle cells when the mucosal layer was present. Radiation eliminated a positive modulatory effect on spontaneous activity by the mucosa layer. Overall, the findings suggest that radiation impairs contractility via mucosal regulatory mechanisms independent of the development of radiation cystitis.