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K-E Andersson

Publications and source records attributed to K-E Andersson.

17 recordsLinked to original sources
PubMed2006

Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate.

OBJECTIVES: With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate. The aim of the present study was to evaluate by means of immunohistochemistry the expression and distribution of some cAMP- and cGMP-PDE isoenzymes in the prostate. MATERIAL & METHODS: Cryostat sections (10 microM) of formaldehyde-fixated tissue segments excised from the transition zone of human prostates were incubated with primary antibodies directed against the PDE isoenzymes 3, 4, 5, and 11. Then, sections were exposed to either fluorescein isothiocyanate- (FITC) or Texas Red- (TR) labeled secondary antibodies and visualization was commenced by means of laser fluorescence microscopy. RESULTS: TR-immunofluorescence indicating the presence of PDE4 (cAMP-PDE) was abundantly observed in the fibromuscular stroma as well as in glandular structures of the transition zone. In contrast to the distribution of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE) was mainly observed in glandular and subglandular areas. No immunostaining for PDE3 (cGMP-inhibited PDE) was detected. CONCLUSION: Our results confirm the presence of PDE isoenzymes 4, 5 and 11 in the transition zone of the human prostate and present evidence that these isoenzymes are not evenly distributed. These findings are in support of the hypothesis that there might be a rationale for the use of PDE inhibitors in the pharmacotherapy of BPH and LUTS.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Muscarinic stimulation of the rat isolated whole bladder: pathophysiological models of detrusor overactivity.

1 Hypotheses as to the pathophysiological basis of bladder detrusor muscle overactivity (DO) have identified both central nervous and peripheral mechanisms as likely contributory factors. In this paper, we describe peripheral autonomous bladder activity in two animal models of DO and discuss how the differences observed between the two models support the likelihood that clinical DO has a multifactorial basis. 2 A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Six adult female spontaneously hypertensive rats (SHR) were compared with normal Wistar controls. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure in response to the muscarinic receptor agonist arecaidine were performed under standardized conditions. 3 In the partially obstructed rat bladder, the amplitude of pressure fluctuations elicited by the muscarinic agonist arecaidine was significantly increased compared with sham-operated animals. The tonic component of the response was no different for the two groups. No difference from controls was apparent in the SHR. 4 We conclude that alterations in autonomous bladder activity in the obstructed rat model suggest that peripheral functional changes contribute to the pathophysiological abnormality. In contrast, the fundamental abnormality in the SHR appears to be at a more central level. The observations support the supposition that lesions at widely separate sites can give rise to apparently similar abnormalities of lower urinary tract function.

Animals↗
PubMed2006

Treatment-resistant detrusor overactivity--underlying pharmacology and potential mechanisms.

Bladder function during filling and micturition is regulated by peripheral and central nervous and hormonal control systems. Micturition occurs in response to afferent signals from the lower urinary tract, and distention of the bladder wall is the primary stimulus. In the animal and human bladder, efferent adrenergic, cholinergic and nonadrenergic, noncholinergic (NANC) neurotransmission has been demonstrated. The most important receptors for activation of contraction are muscarinic (M3) and purinergic receptors (P2X1), however, the contribution of these receptors to contraction may differ between species, and may be changed in bladder dysfunction associated with detrusor overactivity (DO) and/or the overactive bladder (OAB) syndrome, such as outflow obstruction, neurogenic bladders, idiopathic DO and diabetes. The NANC component of the nerve-induced response in such disorders may be responsible for up to 40-50% of the total bladder contraction. Whether this in vitro'atropine-resistance' corresponds to DO/OAB seen in patients not responding to antimuscarinic treatment is not known. Afferent signalling from the urothelium may be involved in both normal bladder function and in DO/OAB, but its role in antimuscarinic-refractory patients remains to be established. Several central nervous system (CNS) transmitters/transmitter systems, including gamma aminobutyric acid (GABA), opioid, serotonin, noradrenaline, dopamine or glutamatergic receptors and mechanisms are known to be involved in micturition control. The contribution of these receptors and mechanisms in DO/OAB resistant to treatment with antimuscarinics is not known, but drugs acting at these sites may offer future treatment possibilities.

Animals↗
PubMed2005

Nocturia: morbidity and management in adults.

Nocturia is an increasingly prevalent and bothersome urinary symptom associated with considerable impact and morbidity in later life. Nocturnal frequency is associated with a number of underlying pathologies, both related and unrelated to the lower urinary tract. Following careful assessment, diagnosis and management, the condition is amenable to amelioration, if not complete cure in the majority of cases. This paper outlines the epidemiology, underlying pathophysiology and diseases associated with nocturia and reviews current treatment strategies.

Adrenergic alpha-Antagonists↗
PubMed2004

[Changes in muscarinic receptors of the aging bladder].

The prevalence of the overactive bladder syndrome (OAB) increases with age. Unfortunately, treatment of the condition is still unsatisfactory. Since muscarinic receptor antagonists are the only effective drug treatment to date, it is logical to assume that muscarinic receptors play an important role in the pathogenesis of OAB. Muscarinic receptors are involved in both the normal and overactive detrusor contraction, and age-dependent changes in muscarinic receptor functions have been found in both animals and human detrusors. In animals as well as humans, two components of detrusor contraction have been demonstrated, the dominating one mediated by muscarinic receptors and the other by ATP (atropine-resistant component). The muscarinic receptor-mediated component decreases with age, and the ATP (purinergic) part increases. However, the clinical consequence of this is unclear, since no major age-dependent changes in the efficacy of antimuscarinic agents in the treatment of OAB have been demonstrated.

Aged↗
PubMed2003

Antimuscarinics and the overactive detrusor--which is the main mechanism of action?

Contraction of the bladder, voluntary or involuntary, involves stimulation of the muscarinic receptors on the detrusor by acetylcholine, released from activated cholinergic nerves. Antimuscarinics are the drugs of choice for treatment of detrusor overactivity and the overactive bladder (OAB) syndrome. However, antimuscarinics at clinically recommended doses have little effect on voiding contractions, and may act mainly during the bladder storage phase, during which there is normally no parasympathetic outflow from the spinal cord. Supporting this, antimuscarinics have been shown to reduce bladder tone during storage, and to increase cystometric bladder capacity. A basal release of acetylcholine from non-neuronal (urothelial) as well as neuronal sources has been demonstrated in isolated human detrusor muscle. It is suggested that this release, which is increased by stretching the muscle and in the aging bladder, contributes to detrusor overactivity and OAB by eventually increasing bladder afferent activity during storage.

Humans↗
PubMed2003

Differences between nocturics and non-nocturics in voiding patterns: an analysis of frequency-volume charts from community-dwelling elderly.

OBJECTIVE: To evaluate differences between elderly people with and without nocturia (waking up in the night to void) in terms of voiding habits, urine production and voided volumes. SUBJECTS AND METHODS: Nocturics or= two voids/night) and non-nocturics (< one void/night) were recruited from a questionnaire survey. Subjects were asked to complete a 3-day frequency-volume chart, including time and volume of each void, and their bedtime and waking time. Diaries from 108 non-nocturics and 116 nocturics were analysed. The number of voids, urine production, largest and average voided volumes were analysed using repeated-measures analysis of variance models, controlling for variables such as age, gender, body weight and gender-diagnosis interaction. RESULTS: Nocturnal urine volume was higher in nocturics than in non-nocturics. The difference between the groups was larger among the men (estimated difference 384 mL) than among the women (227 mL), but highly statistically significant (P < 0.001) in both genders. Among the men the diurnal urine and 24-h urine volumes were significantly higher in nocturics (difference, diurnal 131 mL, 24-h 462 mL, both P < 0.001). In the women the diurnal urine volume was lower in nocturics than in non-nocturics (difference 147 mL P = 0.0022) with no difference detected in 24-h urine volume. The largest voided volume was significantly less in nocturics than in non-nocturics; the difference was larger in women (128 mL, P < 0.001) than in men (42 mL, P = 0.0027). The average voided volume was 85 mL less (P < 0.001) in nocturics. The overlap between the groups in nocturnal urine and voided volumes was substantial and several significant covariates identified. The ratio between nocturnal urine volume and largest voided volume was the most statistically significant predictor of the number of nocturnal voids. CONCLUSION: Elderly nocturics had a higher nocturnal urine production and lower volume per void than non-nocturics. Differences between nocturics and non-nocturics in urine production and largest voided volume did not follow the same pattern in men and women. Nocturia was a result of a mismatch between nocturnal urine volume and largest voided volume, rather than abnormal values in either. The treatment of nocturia should be directed at one or both of these factors, depending on the findings from the 3-day frequency-volume chart of the individual.

Aged↗
PubMed2003

Desmopressin in elderly patients with nocturia: short-term safety and effects on urine output, sleep and voiding patterns.

OBJECTIVE: To investigate the short-term safety of desmopressin in elderly patients with nocturia, with special focus on the risk of hyponatraemia, and to assess the short-term effects on urine output, sleep and voiding patterns. PATIENTS AND METHODS: Patients (72) were recruited from a study using frequency-volume charts, which in turn was preceded by a questionnaire study. Each patient took one 0.2 mg desmopressin tablet at bedtime for three consecutive nights and kept a frequency-volume chart. Serum sodium was assessed in the morning after the first and the third dose. Patients with a mean serum sodium level during treatment deviating more than five units from baseline were considered sensitive to change in serum sodium. Potential predictors for sodium sensitivity and response were investigated with logistic and multiple regression. RESULTS: All 72 enrolled patients completed the trial; no serious adverse events occurred and no adverse events of severe intensity were recorded. Six patients were sensitive to change in serum sodium. The risk (odds ratio, 95% confidence interval) increased with increasing age (1.3, 1.1-1.6), concomitant cardiac disease (10.0, 0.9-105.8) and increasing baseline 24-h urine output (1.2, 1.0-1.5). Patients sensitive to change in serum sodium were pharmacological responders and desmopressin had a greater effect on their 24-h diuresis, indicating that the drug effect was not limited to the night only. CONCLUSION: Desmopressin was well tolerated in elderly patients with nocturia, but the results suggest that serum sodium should be measured before and after a few days of treatment.

Aged↗
PubMed2003

Nocturia and associated morbidity in a community-dwelling elderly population.

OBJECTIVE: To investigate the association between nocturia and selected concomitant diseases and medications in a community-dwelling elderly population. SUBJECTS AND METHODS: Data were obtained with a validated questionnaire mailed to all inhabitants aged >or= 65 years in Tierp, Sweden. Descriptive statistics on age, gender, concomitant diseases and medications were calculated for non-nocturics (subjects reporting a mean of < 1 void/night), intermediate (reporting a mean of 1-2 voids/night) and nocturics (reporting a mean of >or= 2 voids/night). Correlations between the number of nocturnal voids/week and concomitant diseases/medications were investigated with logistic regression, controlling for age and gender. RESULTS: Of the 4264 questionnaires sent, 67% (2866) were returned, of which 73% (2081) were fully evaluable on nocturia and incorporated in the analysis. Of these, 62% reported >or= 1 void/night and 29%>or= 2 voids/night. The median (range) age of the respondents was 74 (65-99) years. The prevalence of nocturia increased with age and men reported more nocturia than women. The nocturic group had the highest percentage of reported disease and medication on each question. In the logistic regression, controlling for age and gender, there was no significant correlation between the number of nocturnal voids and hypertension, angina pectoris or diabetes mellitus, nor with treatment of these diseases. Neither was there any correlation for congestive heart failure, snoring, use of diuretics or hypnotics. There were highly statistically significant correlations (P < 0.001) between the increase in number of nocturnal voids and incontinence, daytime urge and nocturnal thirst. The increase in number of nocturnal voids was negatively correlated with good sleep and with feeling in good health (P < 0.001). CONCLUSION: There was no correlation between the number of nocturnal voids and a known and treated hypertension, angina pectoris, congestive heart failure or diabetes mellitus. The number of nocturnal voids was highly correlated with urge and incontinence.

Age Distribution↗
PubMed2002

Expression of nitric oxide synthase in bladder smooth muscle cells: regulation by cytokines and L-arginine.

PURPOSE: The expression and regulation of the different isoforms of nitric oxide synthase (NOS) in bladder smooth muscle cells are controversial and to our knowledge have not yet been studied systematically. Therefore, the expression and regulation of NOS were studied in rat bladder smooth muscle cells after stimulation with cytokines, lipopolysaccharide and L-arginine. MATERIALS AND METHODS: Primary cell cultures were prepared from rat bladders. The expression of NOS mRNA was examined by reverse transcriptase-polymerase chain reaction and inducible NOS (iNOS) protein expression was studied by Western blot analysis and immunohistochemistry. Nitrite accumulation in the culture medium was determined by the Griess assay. The expression of iNOS was also studied immunohistochemically in whole bladder strips stimulated by cytokines. RESULTS: NOS mRNA expression was not detected in unstimulated cells. Stimulating bladder smooth muscle cells with a cytokine mixture of interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta induced iNOS mRNA and protein expression. The combination of interleukin-1beta plus tumor necrosis factor-alpha appeared to be crucial for iNOS induction in bladder smooth muscle cells. Exposing bladder smooth muscle cells to lipopolysaccharide did not induce iNOS. Adding L-arginine increased nitrite accumulation in cytokine mixture stimulated bladder smooth muscle cells, while iNOS positive cells were detected in the smooth muscle layer of cytokine mixture stimulated bladder strips. CONCLUSIONS: NOS was not detected in unstimulated bladder smooth muscle cells. However, bladder smooth muscle has the potential to express iNOS when exposed to cytokines known to be produced during urinary tract infection.

Animals↗
PubMed2002

Effect of apomorphine on intracavernous pressure and blood pressure in conscious, spinalized rats.

Apomorphine, given subcutaneously (s.c.), induces erection and bladder overactivity in rats through stimulation of dopamine (D1- and D2-like) receptors in the central nervous system. In paraplegic patients, apomorphine was reported to cause bladder overactivity. This suggests that apomorphine may have a spinal site of action also for stimulation of erection. The present study was initiated to evaluate the effect of apomorphine on erectile function in spinalized rats. Apomorphine (100 microg/kg, s.c.) was given to awake, unrestrained male Sprague-Dawley rats (300 g) with or without spinal cord injury, made at the Th 8 level 2 weeks before the experiment. Intracavernous pressure changes from baseline were evaluated as time to first response to apomorphine (TFR; sec), number of phasic pressure changes in the first 30 min (PP30), duration (D; sec) of the phasic pressure changes, the amount of increase in tonic peak pressure (TPP; cmH2O), and burst peak pressure (BPP; cmH2O). Blood pressure (cmH2O) was recorded via an intra-arterial catheter. Apomorphine, 100 microg/kg, caused no significant differences in TFR (217.8 vs 271.2), PP30 (6.4 vs 6.5), D (38.9 vs 37.6.), TPP (51.0 vs 54.0) and BPP (128.9 vs 160.4) between normal (n=8) and spinalized rats (n=6). However, blood pressure decreased significantly more in spinalized than in normal animals (17.7 vs 43.3; P<0.05). The results suggest that both in normal rats, and in rats with spinal cord injury, apomorphine given s.c., can produce erection. This finding supports the use of apomorphine for treatment of erectile dysfunction in paraplegia patients. However, due consideration should be given to possible decreases in blood pressure.

Animals↗
PubMed2002

Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.

PURPOSE: Activation of soluble guanylate cyclase with a subsequent increase in intracellular levels of cyclic guanosine monophosphate is necessary for normal erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1) (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1 modulates erectile responses in the rat. MATERIALS AND METHODS: The effects of YC-1 given intracavernously or intraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronal and endothelial nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted preparations of rat isolated corpus cavernosum. RESULTS: Intracavernous YC-1 (10 micromol. kg.-1) produced erectile responses with a mean intracavernous pressure plus or minus standard error of mean of 81 +/- 17 cm. water (p <0.001) and a mean duration of 7.1 +/- 3.3 minutes (p <0.001). YC-1 (10 micromol. kg.-1) given intraperitoneally also increased the amplitude and duration of erectile responses to cavernous nerve stimulation. Mean peak intracavernous pressure increased from 63 +/- 6 to 10(2) +/- 16 cm. water (p <0.05). Erections induced by a submaximal dose of 25 microg. kg.-1 apomorphine s.c. increased in number after 10 micromol. kg.-1 YC-1 intraperitoneally (p <0.05). In vitro nerve induced relaxant responses were enhanced by increasing concentrations of YC-1. Relaxations at 20 Hz. were increased from a mean of 9% +/- 5% to 52% +/- 5% at a YC-1 concentration of 10(-5) M. (p <0.001). At this concentration carbachol induced relaxations were enhanced from a mean of 19% +/- 3% to 40% +/- 9% (p <0.05). CONCLUSIONS: YC-1 can evoke erectile responses when given intracavernously and it enhances erections induced by cavernous nerve stimulation and apomorphine when given systemically. In vitro YC-1 enhances electrically evoked relaxations in rat corpus cavernosum. YC-1 represents an interesting pharmacological principle that may be useful for treating erectile dysfunction.

Animals↗
PubMed1999

The pharmacological perspective: role for the sympathetic nervous system in micturition and sexual function.

The predominant effects of the sympathetic innervation of the lower urinary tract in man are mediation of contraction of the bladder base and the urethra and inhibition of the parasympathetic pathways at spinal and ganglion levels. Sympathetic tone also mediates the contractility of smooth muscle fibres in the prostatic stroma, and it has an important role in maintaining the penis in a flaccid state and in ejaculation. In the detrusor muscle of most species, beta-adrenoceptors (beta-ARs) mediating relaxation normally dominate over alpha-ARs mediating contraction, and the effect of noradrenaline (NA) is relaxation. The human detrusor is able to express beta(1)-, beta(2)- and beta(3)-ARs and stimulation of beta(3)-ARs causes relaxation. Low, but reproducible expression of alpha(1)-ARs (alpha(1a) and alpha(1d)) has been found in human detrusor muscle, but the alpha(1)-AR subtypes mediating contraction have not been established. The sympathetic pathways to the penis may mediate anti-erectile as well as erectile effects. Although alpha(1) and alpha(2)-ARs have been demonstrated in human corpus cavernosum tissue, available information supports the view of a functional predominance of alpha(1)-ARs. The human vas deferens also has an important adrenergic innervation and alpha(1A)-ARs seem to mediate contraction.

Journal Article↗