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Investigating the Pharmacological Impact of Atosiban, an Oxytocin Receptor Antagonist, on Bladder and Prostate Contractions Within OBESE and Non-Obese Rats

Affiliation
Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia
Badshah, Masroor;
Affiliation
Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia
Ibrahim, Jibriil;
Affiliation
Hull York Medical School, University of Hull, Hull HU6 7RX, UK
Su, Nguok;
Affiliation
Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia
Whiley, Penny;
Affiliation
Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia
Turpin-Nolan, Sarah M.;
Affiliation
Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Riyadh 11533, Saudi Arabia
Elnahriry, Khaled A.;
ORCID
0000-0002-5390-2564
Affiliation
Institute of Anatomy and Cell Biology, Justus-Liebig-University, 35390 Giessen, Germany
Middendorff, Ralf;
ORCID
0000-0001-5706-3932
Affiliation
Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia
Whittaker, Michael;
ORCID
0000-0002-3260-2175
Affiliation
Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia
Exintaris, Betty

Background/Objectives: Lower urinary tract symptoms (LUTS), such as frequency, urgency, nocturia, and urge incontinence, are commonly linked to overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Oxytocin receptor (OXTR) upregulation has been proposed to enhance bladder and prostate contractility, while obesity is a recognized risk factor for LUTS, OAB, and BPH. This study aimed to investigate whether the OXTR antagonist atosiban attenuates spontaneous and oxytocin-induced contractions in bladder and prostate tissues from obese and non-obese rats. Methods: Bladder and prostate tissues were obtained from obese and non-obese rats and studied in in vitro organ bath preparations. The effects of atosiban (1 µM and 10 µM) on spontaneous contractility and oxytocin-induced responses were examined. Immunohistochemistry was performed to evaluate OXTR expression in the bladder. Results: Atosiban significantly reduced spontaneous contractions in the bladder ( p < 0.0001 in obese; p < 0.01 in non-obese) and prostate ( p < 0.01 in obese; p < 0.0001 in non-obese). Oxytocin-induced bladder contractions were significantly increased in obese rats but were attenuated by atosiban at 10 µM ( p < 0.05), an effect absent in non-obese rats. Immunohistochemical analysis confirmed elevated OXTR expression in both epithelial and stromal compartments of the bladder in obese rats ( p < 0.05). Conclusions: These findings indicate that oxytocin contributes to bladder and prostate hypercontractility, particularly in obesity. Targeting OXTR with atosiban may represent a novel therapeutic strategy for the management of LUTS, OAB, and BPH.

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