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Title: Age related differences in responsiveness to sildenafil and tamsulosin are due to myogenic smooth muscle tone in the human prostate
Austin Authors: Lee, Sophie N;Chakrabarty, Basu;Wittmer, Brad;Papargiris, Melissa;Ryan, Andrew;Frydenberg, Mark;Lawrentschuk, Nathan;Middendorff, Ralf;Risbridger, Gail P;Ellem, Stuart J;Exintaris, Betty
Affiliation: Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Melbourne, Victoria, Australia
TissuePath, Melbourne, Victoria, Australia
Department of Surgery, Monash University, Melbourne, Victoria, Australia
Australian Urology Associates, Melbourne, Victoria, Australia
Department of Surgery, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Justus-Liebig-University Giessen, Institute of Anatomy and Cell Biology, Giessen, Germany
Issue Date: 31-Aug-2017
Publication information: Scientific Reports 2017; 7(1): 10150
Abstract: Lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) are highly prevalent in older men, having a profound impact on patient quality of life. Current therapeutics for BPH/LUTS target neurogenic smooth muscle tone, but response is unpredictable and many patients fail to respond. Spontaneous myogenic tone is another component of smooth muscle contractility that is uncharacterized in human prostate. To better understand and improve the predictability of patient response, we defined myogenic contractility using human prostate specimens and examined the effect of existing therapeutics. We show that myogenic activity is present in the human prostate with the frequency of contractions in transition zone (TZ) specimens from BPH diagnosed patients approximately 160% greater than matched controls. α1-adrenoreceptor antagonists (Tamsulosin) and PDE5 inhibitors (Sildenafil) both significantly reduced myogenic contractile parameters, including frequency, with notable interpatient variability. Tamsulosin was more effective in older patients (R(2) = 0.36, p < 0.01) and men with larger prostate volumes (R(2) = 0.41, p < 0.05), while Sildenafil was more effective in younger men (R(2) = 0.45, p < 0.05). As myogenic tone is significantly increased in BPH, therapeutics targeting this mechanism used with reference to patient characteristics could improve clinical outcomes and better predict patient response.
Gov't Doc #: 28860509
DOI: 10.1038/s41598-017-07861-x
ORCID: 0000-0001-8553-5618
Journal: Scientific Reports
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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