Prostatic smooth muscle tone in the guinea pig and human prostate gland

2017-03-01T00:17:22Z (GMT) by Chakrabarty, Basu
An increase in smooth muscle tone in the transition zone of the human prostate gland is a major component associated in the pathophysiology of lower urinary tract symptoms associated with benign prostatic hyperplasia. Spontaneous contractions provide an alternative, perhaps more physiological model of understanding contractility and smooth muscle tone in the prostate gland; however no recordings of spontaneous contractions in the human prostate gland have been documented. The majority of previous studies from our laboratory have focused on recording spontaneous contractions, and the underlying spontaneous electrical activity, in isolated tissue from the guinea pig prostate gland. These recordings are obtained using standard tension recording and intracellular microelectrode electrophysiological techniques, respectively. In this study, the addition of the current ‘gold’ standard in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia, tamsulosin (0.1 nM) had a significantly greater effect on the prostate gland from ageing guinea pig in comparison to adult guinea pigs. In contrast, the addition of tamsulosin (0.3 nM) had a significantly greater effect in adult guinea pigs in comparison to ageing guinea pigs. This demonstrates that a drug associated with an increased clinical efficacy in the treatment of lower urinary tract symptoms, directly reduces, but does not abolish, prostatic smooth muscle tone in the adult and ageing guinea pig prostate gland, prompting the need for further insight into spontaneous contractions in the human prostate gland. A new model of human prostatic smooth muscle tone was developed by creating new protocols for human tissue collection and human tissue experimentation, to successfully obtain recordings of spontaneous contractions in the transition zone of the human prostate gland. The contractility profile of the transition zone of the human prostate gland was significantly different and distinct, in comparison to the peripheral zone from the same patient. The transition zone of the human prostate gland has a significantly greater resting basal tension than the peripheral zone, and is the region where benign prostatic hyperplasia arises. Spontaneous contractions in the transition zone of the human prostate gland are myogenic in nature, and mechanisms involved in the regulation of spontaneous contractions validate what has been previously observed in the guinea pig prostate gland. These include the important role of extracellular Ca2+, intracellular Ca2+, Ca2+-activated Cl- channels, and the nitric oxide pathway, in the regulation of human prostatic smooth muscle tone. Furthermore, clinically used drugs for other disorders utilise underlying mechanisms directly involved in the regulation of human prostatic smooth muscle tone, and may be exploited to treat patients exhibiting lower urinary tract symptoms as a comorbidity. Tamsulosin directly attenuated spontaneous contractions in the transition zone of the human prostate gland. The phosphodiesterase 5 inhibitor, sildenafil, an emerging pharmacotherapy for lower urinary tract symptoms, also directly reduced spontaneous contractions in the transition zone. Despite the inherent variability in tissues from different patients, and responses to different drug treatments, the combination of tamsulosin and sildenafil, had a consistent synergistic effect on the attenuation of human prostatic smooth muscle tone, in comparison to either drug alone. In summary, this model of human prostatic smooth muscle tone provides a novel opportunity to understand lower urinary tract symptoms associated with benign prostatic hyperplasia. Further retrospective analysis with patients’ clinical records will further develop this model of prostatic smooth muscle tone. Targeting human prostatic smooth muscle tone will ultimately improve treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia to improve patient outcomes.