α‐blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms

Pinggera, Germar-M.; Mitterberger, Michael; Pallwein, Leo; Schuster, Antonius; Herwig, Ralf; Frauscher, Ferdinand; Bartsch, Georg; Strasser, Hannes

doi:10.1111/j.1464-410x.2007.07339.x

Cited by 89 publications

(91 citation statements)

References 39 publications

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“…Increased vascular perfusion of the lower urinary tract especially the prostate or bladder neck can result in a beneficial therapeutic effect and decrease LUTS (19).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication

et al. 2012

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Benign Prostatic Hyperplasia (BPH) is a pathological process responsible for the majority of lower urinary tract symptoms (LUTS) in elderly men (1). In addition, erectile dysfunction (ED), which has negative effect on quality of life (QoL), is another major problem of this age group (2).The incidence of BPH increases with age. It is observed in about 50% of men over 50 year with prevalence increasing up to 90% in those older than 80 year. Moreover, 25% to 50% of men with histological confirmed BPH have LUTS (3).The α-blockers and/or 5-α reductase inhibitors are used for the treatment of BPH frequently. The phosphodiesterase inhibitors are Objectives: To evaluate safety and efficacy of tadalafil on lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in patients treated with standard medication. Materials and Methods:In this case-controlled randomized clinical trial, from november 2008 to August 2009, 132 patients with obstructive and irritative urinary tract symptoms due to BPH, IPSS ≥ 8, no indication for surgical intervention and that reached plateau levels of response to treatment were selected. These patients were randomly allocated in two groups (each containing 66 patients). The treatment group received standard treatment of BPH and tadalafil (10 mg nightly); the placebo group received only standard treatment of BPH. IPSS, maximum urinary flow rate (Q max ) and quality of life were assessed before and after a 3-month period of study. Results: Before treatment, mean IPSS, Q max and quality of life values in the treatment and placebo groups were 13.06 ± 4.37 and 13.66 ± 4.25, 8.92 ± 2.96 mL/s and 9.09 ± 2.91 mL/s, 2.93 ± 0.86 and 2.66 ± 0.78, respectively. After treatment, mean IPSS, Q max , and quality of life values in treatment group were 7.66 ± 3.99, 9.99 ± 4.76 mL/s and 1.80 ± 0.98, respectively. These findings were compared to corresponding values of the placebo group (11.37 ± 3.64, 8.73 ± 2.22 mL/s and 2.19 ± 0.53, respectively): IPSS and quality of life were significantly different but Q max didn't show a significant change. Conclusions: Tadalafil improves quality of life and urinary symptoms in patients with LUTS suggestive of BPH, but doesn't have any significant effect on Qmax. Therefore, this drug may be effectively used in combination with standard medical therapies for BPH. Evaluation of

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“…Increased vascular perfusion of the lower urinary tract especially the prostate or bladder neck can result in a beneficial therapeutic effect and decrease LUTS (19).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication

et al. 2012

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“…They concluded that perfusion is reduced in LUTS patients and increases to almost normal levels after α1-blocker treatment, suggesting that treatment improved perfusion in the lower urinary tract (16). However, in the aforementioned work, blood flow at the dome and the posterior wall was not investigated, while perfusion was not measured during bladder emptying.…”

Section: Commentsmentioning

confidence: 97%

The effect of alpha-blocker treatment on bladder hypoxia inducible factor-1 alpha regulation during lower urinary tract obstruction

et al. 2010

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Aims: To determine whether α1-blocker treatment, in chronic bladder outlet obstruction (BOO), influences bladder tissue ischemia. Materials and Methods: This prospective study included 60 patients with BOO, of which 40 were under α1-blocker medication and 20 without treatment. Patients underwent transurethral resection of the prostate (TURP) or suprapubic prostatectomy (SPP). Ten patients with non-muscle invasive bladder cancer underwent transurethral resection of the bladder tumor and served as the control group. Tissue specimens were immunohistochemically stained for hypoxia inducible factor-1α (HIF-1α). Results: Bladder tissue from obstructed subjects showed high immunoreactivity to HIF-1α. The specimens from the control group, showed no or weak, mainly cytoplasmic immunoreactivity to HIF-1α. Patients under α -blocker treatment did not differ in the number of HIF-1α positive cells compared to subjects with no treatment (median number 86.8 [20-150] and 88.6 [0-175], respectively) (p > 0.05). The lowest bladder pressure at which HIF-1α was up regulated, was detected at detrusor pressure Qmax (PdetQmax) = 60 cm H2O. Conclusions: Treatment with α-blockers in obstructed patients considered as non-responders, does not result in HIF-1α down regulation, thus bladder continues to be under chronic stress.

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“…In addition, these drugs improve LUTS without bladder outflow obstruction. Pinggera and colleagues [Pinggera et al 2008a] reported that α 1 -AR antagonists improved bladder blood flow and symptoms in patients with LUTS, and suggested that these drugs might ameliorate LUTS by increasing bladder blood flow.…”

Section: Mouse Modelmentioning

confidence: 99%

Pharmacological treatment of chronic pelvic ischemia

Andersson

Nomiya

Sawada

et al. 2014

Therapeutic Advances in Urology

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Abstract:Epidemiological studies have shown that lower urinary tract symptoms, including overactive bladder, commonly occur in both men and women, with an age-related increase in both sexes. Vascular endothelial dysfunction and urological symptoms are common in the metabolic syndrome; they also occur during the human ageing process and are independent risk factors for the development of atherosclerosis and hypertension. Pelvic arterial insufficiency may lead to impaired lower urinary tract perfusion and play an important role in the development of bladder dysfunction such as detrusor overactivity and overactive bladder. It seems reasonable, but has not been definitely established clinically, that chronic ischemiarelated bladder dysfunction will progress to bladder underactivity. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension, oxidative stress, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. Several types of drug may be able to prevent some of these changes. Even if the α 1 -adrenoceptor blocker, silodosin, the phosphodiesterase type 5 inhibitor, tadalafil, the β 3 -α 1 -adrenoceptor agonist, mirabegron, and the free radical scavenger, melatonin, were unable to prevent the development of neointimal hyperplasia and consequent luminal occlusion in animal models, they all exerted a protecting effect on urodynamic parameters, and on the functional and morphological changes of the bladder demonstrable in vitro. The different mechanisms of action of the drugs suggest that many factors are involved in the pathogenesis of chronic ischemia-induced bladder dysfunction and can be targets for intervention. Since several of the agents tested are used clinically and effectively for relieving lower urinary tract symptoms, the results from animal models of chronic bladder ischemia seem to have translational value. Animal models may be of relevance for designing clinical studies to demonstrate if a certain drug may prevent progression of ischemia-related functional and morphological bladder changes.

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α‐blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms

Cited by 89 publications

References 39 publications

Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication

Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication

The effect of alpha-blocker treatment on bladder hypoxia inducible factor-1 alpha regulation during lower urinary tract obstruction

Pharmacological treatment of chronic pelvic ischemia

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