Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/16830
Title: Age related differences in responsiveness to sildenafil and tamsulosin are due to myogenic smooth muscle tone in the human prostate
Authors: Lee, Sophie N;Chakrabarty, Basu;Wittmer, Brad;Papargiris, Melissa;Ryan, Andrew;Frydenberg, Mark;Lawrentschuk, Nathan L ;Middendorff, Ralf;Risbridger, Gail P;Ellem, Stuart J;Exintaris, Betty
Issue Date: 31-Aug-2017
Citation: 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.
Internal ID Number: 28860509
URI: http://ahro.austin.org.au/austinjspui/handle/1/16830
DOI: 10.1038/s41598-017-07861-x
ORCID: 0000-0001-8553-5618
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/28860509
Type: Journal Article
Appears in Collections:Journal articles

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