Autonomic receptors in human prostate adenomas.

Radioligand receptor binding techniques were used to characterize alpha 1 adrenergic, alpha 2 adrenergic and muscarinic cholinergic (MCh) binding sites in human prostate adenomas obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH). Prostate adenoma specimens were obtained from nine men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). A quantitative symptoms score analysis and urinary flow rate determinations documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The mean equilibrium dissociation constants (Kd) and the mean densities of 125I-Heat (alpha 1 adrenergic) and 3H-NMS (MCh) binding sites were similar in tissue homogenates obtained from men with asymptomatic and symptomatic BPH. The mean Kd of 3H-Rauwolscine (3H-Ra) was significantly greater in the prostatectomy specimens obtained from men with symptomatic BPH compared to the specimens obtained from men with asymptomatic BPH (p less than 0.05). The density of 3H-Ra (alpha 2 adrenergic) binding sites was significantly greater in the prostate adenomas obtained from men with symptomatic BPH compared to the prostate adenomas obtained from men with asymptomatic BPH (p less than 0.05). The difference in alpha 2 adrenoceptor density was accounted for by an increased receptor density in the open prostatectomy specimens. There was no significant correlation between alpha 2 adrenergic, alpha 1 adrenergic, and MCh receptor densities and prostate weight or patient age. This study indicates that the development of infravesical obstruction in men with BPH is not related to upregulation or altered binding affinity of alpha 1 adrenergic or MCh receptor binding sites. The significance of the observed upregulation of alpha 2 adrenoreceptors in the prostate adenomas obtained from men undergoing open prostatectomy is unknown, and requires further investigation.     

The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia.

The specific features of the prostate adenoma predisposing to the development of symptomatic benign prostatic hyperplasia (BPH) are unknown. Our objective was to determine whether the histological composition of the prostate adenoma is related to the development of symptomatic BPH. Prostate adenomas were obtained from men with asymptomatic BPH undergoing cystoprostatectomy for invasive transitional cell carcinoma, and from men with symptomatic BPH undergoing open prostatectomy, transurethral resection of the prostate and pharmacotherapy. The severity of bladder outlet obstruction was evaluated with the Boyarsky symptom score and uroflowmetry. The percentages of stroma, epithelium and glandular lumen were determined in the prostate adenomas via quantitative image analysis on a computer-assisted morphometry system. The prostate adenomas from the 33 men with symptomatic BPH contained 62 +/- 1%, 15 +/- 1% and 23 +/- 1 of stroma, epithelium and glandular lumen, respectively. The prostate adenomas from 6 men with asymptomatic disease contained 54 +/- 1%, 21 +/- 1% and 25 +/- 1% of stroma, epithelium and glandular lumen, respectively. The ratios of stromal-to-epithelial hyperplasia in the prostate adenomas from men with symptomatic and asymptomatic disease were 4.6 +/- 0.3 and 2.7 +/- 0.1, respectively. The differences in percentage of stroma and epithelium, and the stromal-to-epithelial ratio in the prostate adenomas from men with symptomatic and asymptomatic BPH were statistically significant. Our study suggests that the histological composition of the prostate adenoma is related to the development of symptomatic BPH.     

Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia.

The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population.     

Alpha 2 adrenergic receptors in canine prostate: biochemical and functional correlations

The sympathetic innervation of human prostate adenomas has been previously demonstrated using fluorescence microscopy and in vitro isometric studies. A clinical implication of these observations is that bladder outlet obstruction in men with benign prostatic hypertrophy may be subject to pharmacologic manipulation using adrenergic drugs. Randomized clinical trials have demonstrated the efficacy of alpha adrenergic antagonists for symptomatic BPH. We have previously characterized the alpha1 and alpha2 adrenergic receptors in the human prostate using [3H]prazosin and [3H]rauwolscine, respectively. The mean alpha1 and alpha2 receptor densities in the adenomas studied were equivalent. The effect of alpha2 adrenergic drugs on prostatic urethral pressure has not been examined in the human or in an animal model. In this study a canine model was used to define the effect of alpha2 drugs on prostatic urethral pressure. Intravenous administration of clonidine, a selective alpha2 agonist, resulted in a dose dependent increase in prostatic urethral pressure. The maximal increase in urethral pressure ranged between 18 to 30 cm. H2O. The maximal response to clonidine was approximately 50% less than the response to epinephrine, indicating that clonidine acts as a partial agonist. Pretreatment with yohimbine, a selective alpha2 adrenergic antagonist, abolished the effects of clonidine and epinephrine. The alpha2 adrenergic receptors were then studied in the canine prostates using [3H]rauwolscine. The equilibrium dissociation constant, Kd, ranged between 0.68 to 1.80 nM and the receptor density ranged between 14.8 to 69.3 fmol./mg. protein. The receptor density was homogeneous in specimens obtained from the proximal, midportion, and distal canine prostate suggesting that the effect of alpha2 drugs is not sphincter mediated. These in vitro and in vivo studies provide the basis for investigating the effects of alpha2 antagonists in men with symptomatic BPH.     

The effect of electrocautery on neurotransmitter receptor binding assays in the canine prostate

The purpose of this study was to determine whether resection of the prostate with electrocautery alters the binding properties of various neurotransmitter ligands. Prostate glands were removed from four adult male dogs. The prostates were divided in the midsaggital plane and one half of the prostate was resected using a resectoscope. Saturation experiments were performed on the resected and control prostatic tissue using 3H-NMS, 125I-Heat, and 3H-rauwolscine. The mean equilibrium dissociation constants (Kd) and the mean densities of 3H-NMS, 125I-Heat, and 3H-Rauwolscine binding sites were similar in tissue homogenates obtained from control and resected portions of the prostate (p greater than 0.05). Resection of the prostate using electrocautery did not alter the binding properties of various neurotransmitter ligands for characterizing and quantifying muscarinic cholinergic, alpha 1 adrenergic, and alpha 2 adrenergic binding sites in the canine prostate. Approximately 90% of prostatectomies for symptomatic BPH (benign prostatic hyperplasia) are performed transurethrally. The ability to accurately measure neurotransmitter receptor densities in prostate tissues obtained following transurethral resection is imperative for our future studies designed to elucidate the role of alpha adrenergic receptors in the development of bladder outlet obstruction in men with BPH.     

Pharmacological characterization of isolated human prostate

PURPOSE: Human prostate contains alpha-1 adrenergic, cholinergic and nonadrenergic noncholinergic neuroreceptors. Using agonistic and antagonistic agents at these neuroreceptors we studied the resultant contractile responses in isolated human prostate. MATERIALS AND METHODS: Human prostate tissue was obtained at prostatectomy for benign prostatic hyperplasia in 37 adult male patients. Tissues were suspended in tissue bath chambers connected to force displacement transducers. Specimens were subjected to agonist induced contractions, the first always being norepinephrine (NE). Specimens were pretreated with antagonist (adrenergic, cholinergic, nonadrenergic noncholinergic or none if control), followed by contraction with a second agonist (NE or other). Contractile tensions were recorded on a polygraph and then statistically analyzed. RESULTS: The order of highest to lowest agonist induced tensile forces was NE, dopamine, acetylcholine, bethanechol, histamine and serotonin. Excitatory concentration EC(50) values were determined for each agonist tested. Significant differences were found between specific alpha-1 adrenergic receptor blockers (terazosin, prazosin and the experimental drug LY253352). In addition, many other agents antagonized the alpha-1 adrenergic receptor. Inhibitory concentration IC(50) values were obtained and the order of alpha-1 adrenergic antagonistic strengths from strongest to weakest was LY253352, prazosin, terazosin, ketanserin, SCH23390, diphenhydramine, DO710, dopamine, serotonin and histamine. CONCLUSIONS: Human prostate neuroreceptors were determined to be alpha-1 adrenergic, dopaminergic, muscarinic cholinergic, 2A serotonergic and H1 histaminergic. Dopamine, serotonin, histamine and their antagonists blocked the adrenergic response, indicating possible receptor-receptor interaction. Further study of the pharmacology of human prostate would likely identify new drugs for treating patients with bladder outlet obstruction due to benign prostatic hyperplasia.     

Alpha 2 adrenergic receptors in hyperplastic human prostate: identification and characterization using [3H] rauwolscine

[3H]Rauwolscine ([3H]Ra), a selective ligand for the alpha 2 adrenergic receptor, was used to identify and characterize alpha 2 adrenergic receptors in prostate glands of men with benign prostatic hyperplasia. Specific binding of [3H]Ra to prostatic tissue homogenates was rapid and readily reversible by addition of excess unlabelled phentolamine. Scatchard analysis of saturation experiments demonstrates a single, saturable class of high affinity binding sites (Bmax = 0.31 +/- 0.04 fmol./microgram. DNA, Kd = 0.9 +/- 0.11 nM.). The relative potency of alpha adrenergic drugs (clonidine, alpha-methylnorepinephrine and prazosin) in competing for [3H]Ra binding sites was consistent with the order predicted for an alpha 2 subtype. The role of alpha 2 adrenergic receptors in normal prostatic function and in men with bladder outlet obstruction secondary to BPH requires further investigation.     

Clinical and experimental aspects of Adreno‐muscarinic synergy in the bladder base and prostate

Recent clinical trials have shown that combination therapy using an alpha‐receptor antagonist and an antimuscarinic is more effective than either agent alone in improving quality of life and objective urodynamic variables in men with bladder outflow obstruction. There appear to be no negative effects on bladder function. The mode of action of this combination is unknown but presumed to be an antimuscarinic reduction in detrusor overactivity and the alpha‐receptor antagonist reduced outflow tract resistance. We have shown with in vitro experiments that in smooth muscles influencing outflow tract resistance (prostate, trigone) there is a profound contractile synergy between adrenergic and muscarinic pathways. We propose the hypothesis that both arms of the combination therapy reduce contractile tone of the outflow tract and that their simultaneous attenuation has a disproportionately large effect on outflow tract resistance. Our data from trigone muscle suggest that adrenergic and muscarinic receptor activation increase the intracellular [Ca²⁺] but the adrenergic pathway also operates through Ca²⁺‐sensitisation of the contractile apparatus, primarily through a PKC‐dependent pathway. Neurourol. Urodynam. 28:938–943, 2009. © 2009 Wiley‐Liss, Inc.     

Alpha-adrenoceptors and muscarinic receptors in the isolated human prostate

Prostatic specimens of adenomatous tissue (PA) were obtained from the lateral lobe of the prostate in patients with benign prostatic hyperplasia (BPH). Non-hyperplastic specimens of the outer prostatic tissue (PC) were taken from the dorsal part of the prostate in patients undergoing cystourethrectomy. Effects of alpha-adrenoceptor and muscarinic receptor active drugs were studied. Noradrenaline (NA) and the alpha 1-adrenoceptor agonist phenylephrine induced concentration-dependent contractions in PC and PA preparations. The alpha 2-adrenoceptor agonist clonidine was without effect on PC but contracted PA preparations; it was less potent and had less intrinsic activity than phenylephrine. In PC and PA strips, the alpha 1-adrenoceptor antagonist prazosin was more effective than the alpha 2-adrenoceptor antagonist rauwolscine to inhibit NA-induced contractions. Prazosin, but not rauwolscine, inhibited electrically induced contractions in PC strips. The muscarinic receptor agonists acetylcholine and carbachol were without effect in PC and PA preparations. In both PC and PA preparations, clonidine decreased and rauwolscine increased the electrically elicited 3H-efflux after pre-loading of the tissues with 3H-noradrenaline. Carbachol and scopolamine were without consistent effects. In radioligand receptor binding experiments, the occurrence of alpha 1- and alpha 2-adrenoceptor binding sites was demonstrated; the ratio between alpha 1- and alpha 2-adrenoceptor binding sites was 3/2 in PC, but 2/3 in PA tissue. By autoradiography, muscarinic receptors were found to be localized exclusively to the glandular epithelium, consistent with the lack of contractile effects of muscarinic receptor active drugs on PC and PA preparations. Our results thus suggest that the main alpha-adrenoceptor function in human prostatic smooth muscle is of the alpha 1-type and that muscarinic receptors in the prostate are involved in processes other than control of smooth muscle contraction.     

A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.     

Autoradiographic localisation and contractile properties of prostatic endothelin receptors in patients with bladder outlet obstruction

OBJECTIVES: Previous studies have used endothelin (ET) receptor agonists and antagonists to localise ET receptor subtypes in prostatic tissue. We have utilised high affinity ET(A) ([(125)I]PD151242) and ET(B) ([(125)I]BQ3020) receptor-specific radioligands to determine the density and distribution of ET receptor subtypes in prostatic tissues obtained from patients with symptomatic benign prostatic hyperplasia (BPH). The contractile properties of the ET receptor subtypes as well as the effect of ET-1 on alpha(1)-adrenergic receptor-mediated prostatic smooth muscle contraction were assessed. PATIENTS AND METHODS: Saturation binding and quantitative autoradiographic studies were performed using specific radioligands for ET(A) and ET(B) receptors on prostate sections obtained from patients with bladder outflow obstruction secondary to BPH. In vitro isometric tension studies were carried out to characterise the ET receptor subtypes in prostatic smooth muscle strips from the same group of patients. In addition, the effect of ET-1 on alpha(1)-adrenergic receptor-induced prostatic smooth muscle contraction was also investigated. RESULTS: There were dense ET(A) and ET(B) receptor-binding sites in the prostatic stroma. ET(A) receptor-binding sites were also prominent on the prostatic epithelium. ET-1 and sarafotoxin 6 c (ET(B) receptor agonist) elicited prostatic smooth muscle contraction (-log EC(50) 8.31+/-0.15 and 8.22+/-0.22 M, respectively). Both BQ123 (ET(A) antagonist) and BQ788 (ET(B) antagonist) significantly inhibited ET-1- and S6c-mediated prostatic smooth muscle contractile responses, respectively. ET-1 at sub-threshold concentrations significantly enhanced alpha(1)-adrenergic receptor-mediated prostatic smooth muscle contractile responses. CONCLUSIONS: ET(A) receptor-binding sites are prominent in both prostatic stroma and epithelium, whereas ET(B) receptor-binding sites were predominantly seen in the prostatic stroma in symptomatic BPH. Both ET(A) and ET(B) receptors mediate prostatic smooth muscle contraction. ET-1 enhances alpha(1)-adrenergic receptor-mediated contractile responses, suggesting that ET may play a pathophysiological role in bladder outlet obstruction associated with BPH.     

The ability of systematic transrectal ultrasound guided biopsy to detect prostate cancer in men with the clinical diagnosis of benign prostatic hyperplasia.

Multiple directed and systematic ultrasound guided biopsies of the prostate were performed in 73 men with the clinical diagnosis of benign prostatic hyperplasia (BPH). Seven men (10%) had prostate cancer. Of the 67 patients with benign biopsies 40 underwent subsequent transurethral prostatectomy and 2 (5%) had prostate cancer. Multiple directed and systematic biopsies of the prostate detected 78% of the nonpalpable prostate cancers diagnosed in the study population. Radical prostatectomy was performed in all 9 men with prostate cancer: there were 3 small organ-confined tumors, 5 large organ-confined tumors and 1 stage C tumor with 1 focus of microscopic capsular penetration. Our results suggest that multiple directed and systematic ultrasound guided biopsies are capable of detecting low volume nonpalpable prostate cancer in men with BPH. However, the exact indication for pre-treatment ultrasound guided biopsy of the prostate in men with symptomatic BPH remains unclear. It may be that use of this modality is most appropriate for patients undergoing pharmacological therapy or balloon dilation of BPH rather than for those undergoing transurethral prostatectomy.     

Determination of norepinephrine levels in the adult human prostate.

Tissue levels of norepinephrine were measured in prostate tissue from 24 men ranging in age between 41 and 83 years. Prostatic tissue was obtained from men with subtle palpable prostate nodules undergoing transperineal needle biopsy. None of the patients were shown to have histologic evidence of adenocarcinoma. The severity of the symptoms of prostatism was evaluated prospectively using a standardized micturition symptom score questionnaire. Norepinephrine levels were quantified using a sensitive radioenzymatic assay (REA). Overall, the prostates contained relatively high levels of norepinephrine (1666 +/- 124 ng./gm.). Inverse correlations were observed between tissue norepinephrine levels and severity of symptoms of prostatism (r = -0.58; p = 0.003); age (r = -0.53; p = .008); and prostate size (r = -0.48; p = .02). Norepinephrine levels were also measured in tissue specimens obtained from men undergoing enucleation prostatectomy and transurethral resection of the prostate (TURP). The level of norepinephrine in these prostatectomy specimens (115 ng./gm.) was only 14% the level of the prostate biopsy specimens. The relatively low level of norepinephrine in the specimens obtained from patients with symptoms necessitating prostatectomy provides further evidence that norepinephrine levels are inversely related to the degree of symptomatic bladder outlet obstruction.     

Medikamentöse Therapie des benignen Prostatasyndroms

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (>?30–40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.     

Value of the Danish prostate symptom score compared to the AUA symptom score and pressure/flow studies in the preoperative evaluation of men with symptomatic benign prostatic hyperplasia

The Danish Prostate Symptom Score (DAN-PSS) is a new questionnaire for the assessment of lower tract urinary symptoms (LUTS), which claims to be able to predict bladder outlet obstruction. We evaluated the ability of the DAN-PSS to assess LUTS, to predict obstruction, and to predict treatment outcome in men with symptomatic uncomplicated BPH. Twenty-five consecutive men with symptomatic uncomplicated BPH filled in the AUA symptom score and the DAN-PSS and underwent uroflowmetry and pressure-flow studies prior to transurethral prostatic resection (TURP). Patients were reevaluated 4 days and 8 months after surgery. AUA score and DAN-PSS both assessed LUTS and were sensitive to symptom changes after therapy. Compared to pressure/flow studies, neither score correlated with bladder outlet obstruction. Peak urinary flow, however, correlated significantly with obstruction. None of the diagnostic tools used was able to improve patient selection for surgical treatment. The DAN-PSS is a valid and sensitive questionnaire for the assessment of LUTS. It is not able, however, to predict bladder outlet obstruction. In men with uncomplicated BPH, urodynamic evaluation of bladder outlet obstruction did not improve the subjective outcome of TURP. Neurourol. Urodynam. 16:9–18, 1998. © 1998 Wiley-Liss, Inc.     

Effects of pregnancy on adrenergic function in the rabbit urinary bladder

Pregnancy induces morphological as well as functional changes in the urinary tract. Urinary frequency, incontinence, and an increase in residual urine are common clinical findings during gestation. Previous studies from this laboratory have shown a decreased cholinergic response and cholinergic receptor density in the urinary bladders of pregnant rabbits. In the present study, the adrenergic functions of the bladders of pregnant and virgin New Zealand White rabbits were compared using isolated muscle strips. Dose-response curves showed that the contractile responses to epinephrine (alpha and beta agonist) and methoxamine (alpha agonist) were significantly reduced in tissues from the base and the mid-segment, but not the body of the pregnant rabbit bladders. No significant difference was observed in the degree of isoproterenol (beta agonist) induced relaxations between the two groups. Thus, the results demonstrated a decreased alpha responsiveness in the midsegment and base of the pregnant bladders. Physiologically, a decrease in alpha tone at the bladder base would be advantageous for bladder emptying as the resultant relaxation at the bladder outlet theoretically would alleviate the effect of decreased bladder body contractility as well as any mechanical stress imposed on the urethra by the enlarging uterus.     

The function of autonomic receptors in canine ureteral smooth muscle]

I have investigated the effects of autonomic drugs and prostaglandins on in vitro smooth muscle spontaneous contractions and made the quantitative analysis of autonomic receptors in the canine ureter. Ureteral muscle strip cut helically usually generated spontaneous contractions whereas those cut circularly or longitudinally did not generate spontaneous contractions. These results suggest the importance of knowing which direction to cut the ureteral smooth muscle in order to generate spontaneous contractions. Norepinephrine (alpha), phenylephrine (alpha 1), carbachol (muscarinic) and PGF2 alpha caused significant increase in contractile force. Terbutaline (beta 2) and PGE2 caused significant decreases in contractile force, while dobutamine (beta 1) and clonidine (alpha) caused no effect. Autonomic receptor densities were determined using radiology and binding techniques. The number of maximum binding sites (Bmax) of 3H-prazosin (PZ), 3H-yohimbine (YOH), 3H-dihydroaloprenolol (DHA) and 3H-quinuclidinylbenzilate (QNB) were 53.8, 16.9, 11.2 and 5.28 fmol/ml protein, respectively. These data suggest that the contractile responses to adrenergic and cholinergic agonists in the canine ureter are mediated through functional adrenergic (alpha 1, beta 2) and muscarinic cholinergic receptors and that the prostaglandins have a role in the contraction of the canine ureter.     

Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alpha1A and alpha1D-adrenergic receptor antagonist tamsulosin

PURPOSE: Alpha1-adrenergic receptor (alpha1-AR) antagonists are effective for treating patients with lower urinary tract symptoms associated with bladder outlet obstruction (BOO). In humans up-regulation of alpha1-AR function in the detrusor in patients with BOO has been suggested but to our knowledge it is not yet confirmed. We investigated the effect of phenylephrine, an alpha1-AR agonist, on isometric tension in small detrusor muscle biopsies from patients with lower urinary tract symptoms and BOO compared with controls. MATERIALS AND METHODS: Detrusor biopsies were obtained from 7 men with BOO undergoing prostatectomy and 7 undergoing cystectomy for bladder cancer (controls). Patients were characterized by symptom score and urodynamics. Isometric tension was measured in detrusor biopsies with an especially built mini myograph. RESULTS: Mean International Prostate Symptom Score +/- SEM in patients with BOO and controls were 22.3 +/- 2.3 and 4.0 +/- 0.8, respectively. Phenylephrine (10(-6) to 10(-3) M) induced a significant contractile response increase in detrusor biopsies from patients with BOO compared with controls at all concentrations. Tamsulosin (0.1 to 3.0 nM) inhibited phenylephrine induced contraction in a dose dependent manner. CONCLUSIONS: To our knowledge this functional study shows for the first time a highly significant increase in contractile force to phenylephrine in patients with BOO compared with controls. These results suggest up-regulation of alpha1-AR function in BOO since contractile responses were potently inhibited by the alpha1A/D-AR antagonist tamsulosin.     

Medikamentöse Therapie der benignen Prostatahyperplasie

The majority of men with benign prostatic hyperplasia (BPH) seek medical help because of lower urinary tract symptoms (LUTS). Pharmacological treatment of BPH is indicated if the patient has no absolute indications for prostate surgery or benign prostatic obstruction (BPO), but LUTS with a decrease of quality of life. Plant extracts can be prescribed in men with mild to moderate symptoms. α-Blockers can quickly and effectively decrease LUTS and symptomatic disease progression. If patients have predominantly bladder filling symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of an α-blocker plus a muscarinic receptor antagonist is more effective than single drugs used alone. Especially in men with larger prostates, 5α-reductase inhibitors can decrease LUTS and the probability of acute urinary retention as well as need for prostate surgery. The combination of α-blocker plus 5α-reductase inhibitor can reduce LUTS and disease progression more effectively than single drugs.     

Interactions between prostate volume, filling cystometric estimated parameters, and data from pressure-flow studies in 565 men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

The aim of this study was to establish the characteristics and to investigate the interactions between prostate volume, degree of obstruction, bladder contractility, the prevalence of residual volume, bladder compliance, bladder capacities, and the prevalence of instability in a large, well-defined group of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). The 565 consecutive men included in this study met the criteria of the International Consensus Committee on BPH and voided more than 150 mL during uroflowmetry. Their residual urine volume and prostate size were estimated, and filling cystometry and pressure-flow studies were performed. Fifty-three percent of the men appeared to have obstruction. We found a positive correlation between prostate volume and Sch?fer's obstruction grade, except that mean prostate volume decreased at Sch?fer's grades 5 and 6. Significant negative correlations existed between Sch?fer's grade and cystometric bladder capacity and effective capacity. Bladder outlet obstruction results in incomplete emptying. Of all men, 26% had a significant residual volume ( > 20% of cystometric capacity). Thirty-nine percent did not have residual volume. Of the 565 men, 46% had an unstable bladder. In particular, patients with an unstable bladder in the sitting and lying positions have a significantly higher Sch?fer's grade and contractility grade and a significantly lower cystometric and effective bladder capacity compared with patients without instability. Patients with a residual volume or instability were significantly older. We conclude that in men with LUTS suggestive of BPH, abnormalities of bladder and bladder outlet function vary greatly and have complex mutual interactions.