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Karl-Erik Andersson

Publications and source records attributed to Karl-Erik Andersson.

At least 19 recordsLinked to original sources
PubMed2003

Nerve-mediated bladder contraction is impaired by cytokines: involvement of inducible nitric oxide synthase.

We investigated the possible involvement of inducible nitric oxide synthase (iNOS) in the effect of cytokines on neuromuscular function in isolated rat bladder strips. Bladder strips were incubated in cell culture medium for 24 h with or without tumour necrosis factor-alpha (TNF-alpha)+interleukin-1beta. Mechanical activity in response to electrical field stimulation and carbachol was recorded in organ baths. Both the electrical field stimulation- and carbachol-induced contractions were reduced by the incubation. The electrical field stimulation-induced contraction was significantly further impaired after prolonged exposure to TNF-alpha+interleukin-1beta. This impairment was restored by dexamethasone, the iNOS inhibitor aminoguanidine and partially by brain-derived neurotrophic factor (BDNF). In contrast, carbachol-induced contractions were not affected by cytokines. iNOS protein expression was detected in cytokine-incubated bladder strips by immunohistochemistry and Western blot analysis. The results demonstrated that TNF-alpha+interleukin-1beta impaired nerve-mediated bladder contractions. Aminoguanidine, and to some extent BDNF, exerted neuroprotective effects.

Animals↗
PubMed2003

Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats.

Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP. Cystometric investigations were performed on awake female Sprague-Dawley rats before and 24 h after injection of RTX (0.3 mg/kg s.c.) or vehicle. The effects of intravesically instilled ATP (0.1 or 1.0 mM), capsaicin (30 microM) or acetic acid (pH 4.0) were compared with those of intravesical saline. RTX, but not its vehicle, significantly increased threshold pressure, voiding interval, micturition volume and bladder capacity. In the vehicle-pretreated rats, intravesical instillation of capsaicin or acetic acid significantly decreased voiding interval, micturition volume, and bladder capacity. However, in the RTX-pretreated rats, neither capsaicin nor acetic acid affected any parameter. On the other hand, intravesical ATP (0.1 mM) significantly decreased voiding interval and micturition volume in both groups of animals. At 1.0 mM, ATP also increased basal pressure and decreased the pressure threshold for micturition in both groups. The present results support the view that increased extracellular ATP has a role in mechano-afferent transduction in the rat bladder and that ATP-induced facilitation of the micturition reflex is mediated, at least partly, by nerves other than capsaicin-sensitive afferent nerves.

Acetic Acid↗
PubMed2003

Actions of tramadol on micturition in awake, freely moving rats.

1 (+/-)-Tramadol, a widely used analgesic, is a racemate stimulating opioid receptors and inhibiting reuptake of noradrenaline and serotonin, that is, pharmacological principles previously shown to influence rat micturition. 2 We studied both (+/-)-tramadol and its enantiomers in conscious Sprague-Dawley rats undergoing continuous cystometry. The effects of these agents were compared to those of morphine ( micro -opioid receptor agonist) and tested after pretreatment with naloxone ( micro -opioid receptor antagonist). Cystometries were evaluated before and after intravenous (i.v.), intraperitoneal (i.p.) and intrathecal (i.t.) drug administrations. 3 The most conspicuous effects of i.v. (+/-)-tramadol (0.1-10 mg kg(-1)) was an increase in threshold pressure and an increase in micturition volume. 4 These effects were mimicked by (+)-tramadol (0.1-5 mg kg(-1) i.v.), whereas (-)-tramadol (5 mg kg(-1) i.v.) did not influence threshold pressure and micturition volume. 5 The effects of (+/-)-tramadol 5 mg kg(-1) on micturition volume were blocked by pretreatment with naloxone 0.3 mg kg(-1). Morphine (0.3-10 mg kg(-1) i.p.) increased threshold pressure but did not significantly increase micturition volume in doses not resulting in overflow incontinence. 6 (+/-)-Tramadol 10 mg kg(-1) increased urine production, an effect blocked by desmopressin 25 ng kg(-1). 7 (+/-)-Tramadol effectively inhibits micturition in conscious rats by stimulating micro -opioid receptors. A synergy between opioid receptor stimulation and monoamine reuptake inhibition may contribute to the micturition effects.

Animals↗
PubMed2003

Morphology, phenotype and ultrastructure of fibroblastic cells from normal and neuropathic human detrusor: absence of myofibroblast characteristics.

PURPOSE: Fibroblasts are functionally diverse and fibroblastic cells with smooth muscle-like characteristics (myofibroblasts) regulate smooth muscle activity in certain tissues. The presence of myofibroblasts has been reported in the bladder with important implications for normal function and detrusor overactivity. We assessed fibroblastic cell characteristics to discern features suggesting a myofibroblast phenotype in normal or neuropathic human detrusor. MATERIALS AND METHODS: A total of 25 control samples were obtained from cadaveric organ donors or patients with a mean age of 42.3 years investigated for hematuria and compared with samples from 18 patients with a mean age of 37.4 years with neurogenic detrusor overactivity. Morphology, phenotypic expression of various markers and the ultrastructure of each fibroblastic cell visible in multiple sections from each specimen was evaluated by 2 independent assessors. RESULTS: Fibroblastic cells were observed throughout the smooth muscle and connective tissue. They were located peripherally on muscle fascicles and had a polar stellate appearance with processes ramifying in interfascicular planes and muscle. They possessed vimentin-like immunoreactivity and weak c-kit-like immunoreactivity but not desmin or alpha-smooth muscle actin-like immunoreactivity. Ultrastructurally they showed dilated rough endoplasmic reticulum with a moderately electron dense amorphous content and prominent golgi complexes. Nuclei had clumped peripheral heterochromatin. There were extensive flattened processes that lacked basal laminae. There was no specific contact with nerve fibers or smooth muscle. Neuropathic bladder samples did not differ overtly from those of controls. CONCLUSIONS: The detrusor possesses an extensive network of fibroblastic cells and processes. No evidence of myofibroblast differentiation was discerned in normal or neuropathic detrusor, although a minority subpopulation or regional variability in cellular phenotype could not be excluded.

Adult↗
PubMed2003

Expression of nitric oxide synthase immunoreactivity in the human female intramural striated urethral sphincter.

PURPOSE: While we have recently detected neuronal nitric oxide synthase (nNOS) immunoreactivity in a heterogeneous population of human male urethral striated muscle, to our knowledge the association of nNOS in the female counterpart is unknown. We investigated the association of nNOS with female urethral striated muscle and re-investigated muscle fiber types. MATERIALS AND METHODS: Cryostat sections were taken from the middle third of 4 human female urethras. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and nNOS immunohistochemistry were performed. Muscle fiber types were identified by myofibrillar adenosine triphosphatase histochemistry and fast twitch troponin T immunohistochemistry. The association between nNOS immunoreactivity and muscle fiber type was analyzed. RESULTS: Positive staining for nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and nNOS immunoreactivity were recognized in the sarcolemma of 43.9% of female urethral striated muscle fibers. Immunoreactivity for fast twitch troponin T immunohistochemistry was demonstrated by 2% of the striated fibers. The use of myofibrillar adenosine triphosphatase showed that all fibers darkly stained uniformly at a pH of 9.6, 4.6 and 4.3, suggesting that they were myofibrillar intermediate muscle fibers. The results allowed the differentiation of 2 subgroups of fibers, namely smaller fibers (modal diameter 10.1 to 15.0 microm.) without nNOS immunoreactivity and larger fibers (modal diameter 15.1 to 20.0 microm.) with nNOS immunoreactivity. CONCLUSIONS: To our knowledge female urethral striated muscle has for the first time been found to consist of myofibrillar intermediate fibers and nNOS was positively localized in the sarcolemma of a subgroup of the fibers. This study provides a basis for further investigation into female urethral striated sphincter function and changes in pathological conditions.

Adenosine Triphosphatases↗
PubMed2003

Tramadol inhibits rat detrusor overactivity caused by dopamine receptor stimulation.

PURPOSE: In patients with Parkinson's disease an imbalance between stimulatory D2-like receptors and inhibitory D1-like receptors may contribute to detrusor overactivity. Apomorphine, which stimulates D1-like and D2-like dopamine receptors, induces detrusor overactivity in rats. Tramadol is an analgesic drug that stimulates opioid receptors and inhibits reuptake of serotonin and noradrenaline. To evaluate a potentially inhibitory effect of tramadol the drug was given to rats with apomorphine induced detrusor overactivity. MATERIAL AND METHODS: Female Sprague-Dawley rats were used. During anesthesia catheters were introduced into the bladder dome, femoral vein and subcutaneously (SC). Three days later the rats were placed in a metabolism cage and voiding was stimulated by infusing saline into the bladder. Micturition parameters were recorded and compared after the administration of apomorphine and tramadol or vehicle. Desmopressin was given as pretreatment to suppress the diuresis produced by tramadol. RESULTS: While 30 microg kg-1 apomorphine SC was devoid of effect, 60 and 100 microg kg-1 apomorphine SC induced a transient detrusor overactivity. Tramadol (1 mg kg-1) was without effect but 5 and 10 mg kg-1 tramadol intravenously attenuated the effects of apomorphine, while inducing prominent diuresis. Pretreatment with desmopressin, which did not alter cystometry or the effects of apomorphine, abolished diuresis. In these rats 5 and 10 mg kg-1 tramadol intravenously abolished the overactivity caused by apomorphine SC. CONCLUSIONS: Tramadol effectively suppresses apomorphine induced detrusor overactivity in doses shown to have analgesic activity. Hence, tramadol may provide an approach to treat lower urinary tract disorders in which dopamine receptor activation is involved.

Analgesics, Opioid↗
PubMed2003

Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder.

PURPOSE: Autonomous bladder activity can take the form of localized micromotions (MMs), suggesting that the detrusor may be arranged into component modules, of which each is capable of contracting autonomously. We examined MMs in isolated whole rat bladder and the effects of partial bladder outlet obstruction as a model of detrusor overactivity (DO) to ascertain whether altered modular activity could be an etiological factor in DO. MATERIALS AND METHODS: A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure and simultaneous registration of intramural contractions were performed under standardized conditions. RESULTS: Prior to filling MMs took the form of localized contractions near the vesicoureteral junction in sham operated animals and multifocal microcontractions in obstructed animals. Intravesical volume increases were associated with a change in localized MMs to propagated contraction waves. In sham operated animals stretch resulted in increased MM frequency but decreased amplitude. After obstruction stretch elicited highly coordinated MMs and enhanced intravesical pressure transmission. The time since surgery did not alter observations in the sham or obstructed group. CONCLUSIONS: Detrusor muscle in isolated bladders under conditions modeling urine storage may have a functional modular arrangement with the basolateral region most active prior to filling. Peripheral factors determining intravesical pressure include the number of modules active, coordination and intramural tension at other sites. After bladder outlet obstruction more modules are active at baseline and their coordination is enhanced by stretch, leading to increased pressure fluctuations. Such changes may contribute to the development of DO.

Animals↗
PubMed2003

Bladder overactivity in mice after 1 week of outlet obstruction. Mainly afferent dysfunction?

PURPOSE: Partial bladder outlet obstruction (BOO) is an established way to create bladder overactivity in animals. However, the micturition pattern achieved can vary considerably. We investigated the correlation between different micturition patterns, post-void residual urine, bladder capacity, bladder weight and in vitro contractility in a conscious mouse model of BOO. MATERIALS AND METHODS: Female MNRI mice with moderate (urethral) outlet obstruction were used. After 7 days of BOO cystometry without anesthesia was performed with the animal in a metabolic cage. Results were compared with those in unoperated controls and sham operated animals. In vitro contractility studies were performed. RESULTS: The majority of obstructed animals had an overactive voiding pattern with increased nonvoiding detrusor activity and without increased bladder weight. The remaining obstructed animals had significantly increased bladder weight and normal micturition volume but increased threshold pressure, bladder capacity and post-void residual urine. Subtle in vitro differences were found among the groups. CONCLUSIONS: The urodynamic characteristics of BOO mice correlate with bladder weight. However, detrusor overactivity in obstructed mice may develop without an increase in bladder weight and with only subtle changes in smooth muscle function, as investigated in vitro. This observation suggests that major disturbances caused by BOO may lie in the afferent arm of the signaling pathway.

Animals↗
PubMed2003

Erectile physiological and pathophysiological pathways involved in erectile dysfunction.

PURPOSE: The importance of signaling pathways in penile smooth muscles involved in normal erection and erectile dysfunction (ED) is discussed based on a review of the literature. MATERIALS AND METHODS: Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents but also by visual, olfactory and imaginary stimuli. The generated nervous signals will influence the balance between the contractant and relaxant factors, which control the degree of contraction of penile smooth muscles and, thus, determine the functional state of the penis. The different steps involved in neurotransmission, impulse propagation and intracellular transduction of neural signals may be changed in different types of erectile dysfunction. RESULTS: Recent findings have suggested an important role for RhoA/Rho kinase in the regulation of cavernosal smooth muscle tone and that changes in this pathway may contribute to ED in various patient subgroups, eg diabetes and vascular disease. Neurogenic nitric oxide is still considered the most important factor for immediate relaxation of penile vessels and corpus cavernosum. However, endothelially generated nitric oxide seems essential for maintaining erection. Endothelial dysfunction can contribute to ED in several patient subgroups. In addition, in conditions associated with reduced function of nerves and endothelium, such as aging, hypertension, smoking, hypercholesterolemia and diabetes, circulatory and structural changes in the penile tissues can result in arterial insufficiency and defect muscle relaxation. CONCLUSIONS: Different types of ED often have overlapping pathophysiologies but may also have common pathways contributing to ED. Such pathways may be potential treatment targets.

Amides↗
PubMed2003

Estrogen receptor subtypes and afferent signaling in the bladder.

PURPOSE: The influence of estrogen on bladder function has been the subject of several experimental and clinical studies. In addition to the well-known estrogen receptor (ER)alpha, recently the ER subtype ERbeta was discovered. We investigated potential changes in bladder function in mice lacking either 1 or both receptor subtypes compared with WT mice. MATERIALS AND METHODS: Female mice lacking genes for ERalpha (ERKO), ERbeta (BERKO) or both and their WT littermates were used for the study. Continuous cystometry in awake animals was performed before and after intravesical administration of capsaicin. In addition, in vitro responses to electrical field stimulation before and after incubation with scopolamine and alpha,beta-methylene adenosine triphosphate, and to carbachol were investigated. RESULTS: Control cystometry revealed no significant difference in urodynamic parameters among all strains. After capsaicin instillation the micturition interval and volume decreased, and micturition pressure increased in WT, ERbeta and 2 gene mice, while no changes were seen in ERKO mice. In vitro contractility was similar in all groups. Incubation with scopolamine and alpha,beta-methylene adenosine triphosphate led to significant decreases in the response to electrical field stimulation. There was no difference in the response to carbachol among the groups. CONCLUSIONS: The lack of ERalpha and/or ERbeta had little effect on in vitro contractility or on continuous cystometry in awake animals. The lack of response to capsaicin instillation in ERKO suggests that ER subtypes are important for vanilloid receptor function and mechano-afferent signaling.

Animals↗
PubMed2003

Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo.

Bladder overactivity associated with outflow obstruction is a common human condition recapitulated in the female rat by narrowing the diameter of the urethra. The goal of these studies was to evaluate the role of intercellular communication through connexin43 (Cx43)-derived gap junction channels to bladder overactivity following partial urethral outflow obstruction of 3-day to 6-wk duration. Cx43 mRNA and protein expression were barely detectable by Northern or Western blots, respectively, in the detrusor layer of normal bladders, but bands were found with both techniques after 6 wk of obstruction. Linear regression analysis of the RT-PCR data revealed a statistically significant positive correlation between the duration of obstruction (again, ranging from 3-day to 6-wk duration) and Cx43 mRNA transcript levels, such that after 6 wk of obstruction, Cx43 transcript levels were approximately 15-fold greater than initial control values. When taking into account the approximately fivefold increase in bladder weight over this same time frame, the absolute amount of Cx43 mRNA in the bladder apparently increased by approximately 75-fold. In that regard, as anticipated, and consistent with previous observations, 6 wk of obstruction was also associated with a significant increase in spontaneous bladder contractions between micturitions. The amplitude of these contractions was significantly reduced by heptanol given intravesically. Furthermore, carbachol-precontracted bladder strips from obstructed animals were more sensitive to heptanol-induced relaxation (100 microM) than their unobstructed counterparts (n = 6; P < 0.01). When bladder strips were equivalently precontracted via electrical field stimulation (EFS; 20 Hz), similar heptanol-induced relaxation responses were observed. However, the tetrodotoxin-resistant portion of the EFS-induced contraction was greater in the obstructed than in the unobstructed animals, and this portion of the contractile response was more sensitive to heptanol-induced relaxation in obstructed than unobstructed bladders (n = 7; P < 0.01). Taken together, these observations indicate that partial outlet obstruction produces an overactive bladder that may be more dependent on intercellular communication through gap junctions for modulation of contractile responses than its normal counterpart.

Animals↗
PubMed2002

Effects of NAD-299, a new, highly selective 5-HT1A receptor antagonist, on bladder function in rats.

5-HT is involved in micturition control. In the rat, stimulation of the 5-HT(1A) receptor excites, whereas 5-HT(1A) receptor antagonism inhibits micturition. The present study examined the effects of a new, highly selective, 5-HT(1A) receptor antagonist, NAD-299, on micturition in rats. Comparisons were made with WAY100635, a well-characterised antagonist at the 5-HT(1A) receptor. Female Sprague-Dawley rats, conscious or anaesthetised, were used for cystometric studies. Intravenous (i.v.), intraarterial (i.a.), intrathecal (i.t.) or intracerebroventricular (i.c.v.) catheters were implanted for drug administration. In vitro, rat bladder strips were contracted by carbachol or electrical stimulation of nerves. The effects of NAD-299, WAY100635 and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT(1A) receptor agonist) on cystometric parameters and contraction of bladder strips were recorded. In conscious rats, i.v. NAD-299 and WAY100635 at 1 micro mol kg(-1) increased bladder capacity (24+/-13% and 27+/-19% respectively) and decreased micturition pressure (16+/-8% and 12+/-10% respectively). Given i.a., 5-HT 0.25 micro mol kg(-1) and 8-OH-DPAT 0.37 micro mol kg(-1) stimulated micturition. The effect of 8-OH-DPAT, but not those of 5-HT, was blocked by i.a. NAD-299. 8-OH-DPAT 0.03 micro mol given i.t. or i.c.v. stimulated micturition, an effect blocked by WAY100635 0.1 micro mol, given i.t or i.c.v. NAD-299 or WAY100635 (0.1 micro mol i.t.) were without significant effects, but given i.c.v. at 0.1 micro mol both drugs increased bladder capacity (34+/-12% and 22+/-13% respectively). Neither NAD-299 nor WAY100635 up to 10(-5) M had effects on electrically- or carbachol-induced contractions of rat bladder strips. NAD-299 1 micro mol kg(-1) i.v. suppressed oxyhaemoglobin-induced detrusor over-activity. It is concluded that NAD-299, acting at a supraspinal site, can inhibit micturition in the rat.

Animals↗
PubMed2002

Effects of beta(3)-adrenoceptor stimulation on prostaglandin E(2)-induced bladder hyperactivity and on the cardiovascular system in conscious rats.

AIMS: To investigate the effects of selective beta(2)- and selective beta(3)-adrenoceptor (AR) agonists on prostaglandin (PG) E(2)-induced bladder hyperactivity in conscious free-moving rats. METHODS: Female Sprague-Dawley rats were anesthetized for implantation of bladder, intravenous, and intra-arterial catheters. The effects of a beta(3)-AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE(2) (20-60 microM, 6 mL/hr) in conscious rats produced a concentration-dependent increase in voiding frequency. RESULTS: In this model i.v. CL316,243 (beta(3)-AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a dose-dependent manner, without affecting threshold pressure or micturition pressure. On the other hand, i.v. procaterol (beta(2)-AR agonist) did not counteract the bladder hyperactivity. Atropine (muscarinic antagonist) reduced micturition pressure and micturition volume, and shortened micturition interval. CL316,243 slightly decreased mean blood pressure and increased heart rate only when given at high doses (10 and 100 microg/kg, i.v.). In contrast, procaterol caused a significant decrease in mean blood pressure and a significant increase in heart rate. Atropine significantly increased heart rate. CONCLUSIONS: The present results clearly demonstrated that the beta(3)-AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on beta(3)-AR stimulation. Provided that these results are valid in humans, selective beta(3)-AR agonists might be clinically useful for controlling a certain type of bladder overactivity.

Adrenergic beta-2 Receptor Agonists↗
PubMed2002

Role of supraspinal serotonin receptors for micturition in normal conscious rats.

Serotonin (5-HT) receptors are widely distributed in the central nervous system, including several areas involved in the control of micturition reflex pathways. However, the roles of the different subtypes of 5-HT receptors are not well known. We studied in normal, conscious rats, the effects on the cystometrogram of intracerebroventricular (i.c.v.) administration of 5-HT, 8-hydroxy-2-(di-N-propylaminotetralin) (8-OH-DPAT; agonist at 5-HT(1A) receptors), alpha-methyl-5-hydroxytryptamine maleate (agonist at 5-HT(2) receptors), 2-methyl-5-hydroxytryptamine hydrochloride (agonist at 5-HT(3) receptors), and 1-(4-amino-5-chloro-2methoxyphenyl)-3-(1-n-butyl-4piperidinyl)-1-propanone hydrochloride (RS67506; agonist at 5-HT(4) receptors). Female Sprague-Dawley rats, weighing approximately 230 g, were used. A polyethylene catheter was inserted into the bladder through the dome for cystometric investigations. For administration of drugs, a catheter was implanted into the right cerebral ventricle. Three days after implantation of the bladder catheter, continuous cystometry was performed. Administration of 5-HT (6 nmol/kg i.c.v.), 8-OH-DPAT (6 nmol/kg), alpha-methyl-5-hydroxytryptamine maleate (6 nmol/kg), or RS67506 hydrochloride (6 nmol/kg) significantly (P < 0.05) increased micturition pressure and decreased bladder capacity and micturition volume. The effects increased in a dose-dependent manner (18, 60 nmol/kg). Intracerebroventricular administration of 2-methyl-5-hydroxytryptamine hydrochloride (60 nmol/kg) caused no change in the cystometric parameters. The results suggest that in normal conscious rats, at the supraspinal level, 5-HT (via 5-HT(1A), 5-HT(2), and 5-HT(4) receptors) can enhance the micturition reflex induced by bladder filling. Whether this means that 5-HT(1A), 5-HT(2), and 5-HT(4) receptors can be targets for drugs meant for treatment of bladder hyperactivity, should be explored.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Tamsulosin: an overview.

This article reviews the contemporary literature related to tamsulosin, which is now the most widely used alpha antagonist in treating benign prostatic hyperplasia. The primary emphasis of this article is on the clinical data that exist related to this agent. Currently, there are no adequate studies that effectively compare existing agents for the treatment of benign prostatic hyperplasia using a randomised, placebo-controlled design with adequate numbers and this needs to be addressed in future studies.

Adrenergic alpha-Antagonists↗
PubMed2002

Future drugs for the treatment of benign prostatic hyperplasia.

For at least a decade, no new drug principles have been added to the therapeutic armamentarium for the treatment of lower urinary tract symptoms (LUTS) associated with or suggestive of benign prostatic hyperplasia (BPH). Theoretically, there seem to be several possibilities to improve the current treatment, which is based mainly on alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors and phytotherapy. It cannot be dismissed that subtype selective alpha1-AR antagonists can further improve treatment, but convincing evidence is still lacking. Muscarinic receptor antagonists are currently evaluated in BPH patients, but their eventual place in therapy, as a single treatment or in combination with alpha1-AR antagonists, has to be established. Endothelin receptor antagonists, alone or together with alpha1-AR antagonists, seem to offer a new attractive approach; however, proof of concept studies are lacking. The L-arginine/NO/cGMP pathway awaits further exploration; nitric oxide (NO) donors or phosphodiesterase (PDE) inhibitors may be clinically useful. Purinoceptors are currently the focus of interest as treatment targets in the lower urinary tract and inhibitors of P2X3 (and P2X1) subtypes may offer new opportunities. If a treatment based on desensitising C-fibres in the bladder and urethra is effective, not only in neurogenic bladders, but also for treating LUTS, it would be a viable option. For new treatments of LUTS, targets within the central nervous system (CNS) may offer exciting opportunities.

Adrenergic alpha-Antagonists↗
PubMed2002

alpha-Melanocyte stimulating hormone and oxytocin induced penile erections, and intracavernous pressure increases in the rat.

PURPOSE: alpha-Melanocyte stimulating hormone (alpha-MSH; Fluka Chemie AG, Geneva, Switzerland) and oxytocin induce erection in rats after intracerebroventricular administration. We studied possible interactions of alpha-melanocyte stimulating hormone with mechanisms pertaining to oxytocin or nitric oxide. MATERIALS AND METHODS: We used 78 anesthetized male Sprague-Dawley rats. Catheters were implanted in the lateral cerebral ventricle or into the subarachnoid space at L6 to S1. Intracavernous pressure was documented and arterial blood pressure was directly measured. RESULTS: Intracerebroventricular alpha-MSH (3 microg.) produced a mean of 2.6 +/- 0.6 erectile responses (p <0.05) with a mean duration of 3.4 +/- 1.1 minutes (p <0.05). Mean peak intracavernous pressure was 114 +/- 8 cm. water. An intracerebroventricular dose of 100 microg. N-nitro-L-arginine-methyl ester HCl (Sigma Chemical Co., St. Louis, Missouri) given in intracerebroventricular fashion abolished alpha-MSH induced erectile responses, whereas intracerebroventricular administration of 500 ng. of the oxytocin receptor antagonist l-deamino, 2-D-Tyr(Oet), 4-Thr, 8-Orn-OT (Ferring AB, Malmö, Sweden) had no effect. Intracerebroventricular oxytocin (30 ng.) induced a mean of 3.2 +/- 0.9 erectile responses (p <0.05) with a mean peak intracavernous pressure of 81 +/- 8 cm. water and a mean duration of 3.3 +/- 1.1 minutes. Intrathecal alpha-MSH (3 microg.) did not produce any erectile responses, whereas a mean of 5.7 +/- 0.9 responses (p <0.001) with a mean peak intracavernous pressure of 142 +/- 8 cm. water and mean duration of 5.0 +/- 1.3 minutes was obtained with 30 ng. oxytocin intrathecally. Responses induced by intrathecal oxytocin were abolished by 100 microg. N-nitro-L-arginine-methyl ester HCl intrathecally. CONCLUSIONS: We confirmed by monitoring intracavernous pressure and blood pressure that supraspinal erectile responses induced by alpha-melanocyte stimulating hormone involve effects mediated by nitric oxide but are independent of oxytocinergic mechanisms. At the spinal level oxytocin produces erectile responses involving nitric oxide. alpha-Melanocyte stimulating hormone does not seem to have a spinal site of action.

Animals↗