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#167

Amelioration of benign prostatic obstruction by the soluble guanylate cyclase activator, cinaciguat, in aged male mice—evaluated using novel telemetric cystometry Ikeda Y1, Zabbarova I1, Kozlowski M1, Kanai A1 1. University of Pittsburgh KEYWORDS: Animal Study, Benign Prostatic Hyperplasia (BPH), Pathophysiology, Pharmacology, Bladder Outlet Obstruction Lower urinary tract (LUT) symptoms secondary to benign prostatic hyperplasia (BPH) and obstruction (BPO) are highly prevalent in the aging male population. Currently available pharmacotherapies include α-adrenoceptor antagonists, aromatase inhibitors and phosphodiesterase type 5 inhibitors. However, refractoriness and limited efficacy are issues with these agents as demonstrated by the high number of BPO surgeries performed each year. Accordingly, there is a significant need for more effective therapeutic option. Our data indicate that daily treatment of aged mice with the soluble guanylate cyclase (sGC) activator, cinaciguat, reduces hyperplasia within the prostatic urethra and surrounding region encircled by the external urethral sphincter (EUS), relieving urethral compression. Therefore, our aim was to determine whether prostatic hyperplasia in mice correlates with functional outlet obstruction and the effects of cinaciguat treatment. To achieve this, we implanted telemetric pressure sensors into the bladders of adult and aged male mice. Pressure recordings from awake freely mobile mice were combined with customized metabolic cages equipped with high sensitivity load cells. These allowed recording of small voided volumes at high acquisition rates to facilitate extrapolation of urine flow rate. This novel methodology allowed us to demonstrate for the first time a naturally occurring BPO, defined by high micturition pressures and low flow rates, in aged male mice supporting their use as a preclinical model for the study of BPH/BPO. Read the full abstract text here: https://www.ics.org/2020/abstract/167