Anders Mattiasson

Cystometrical Evaluation of Bladder Instability in Rats with Infravesical Outflow Obstruction

Cystometries were performed in normal rats and in rats with bladder hypertrophy due to infravesical outflow obstruction. Investigations were performed in the presence and absence of anesthesia. pentobarbital anesthesia depressed spontaneous contractile activity in the bladder and the micturition reflex, thereby making measurements of other variables, such as bladder capacity and residual volume, impossible. In conscious animals infravesical outflow obstruction led to development of increased bladder capacity, marked residual volume, and unstable detrusor contractions. The model seems to be well suited for further evaluation of the mechanisms involved in the development of detrusor instability and the responses to pharmacological treatment.

Atropine Resistance of Transmurally Stimulated Isolated Human Bladder Muscle

Human detrusor strips were obtained from patients undergoing reimplantation of ureters because of reflux, transvesical prostatectomy, or cysto-urethrectomy en bloc because of bladder malignancy. The strips were electrically stimulated. A frequency-dependent contractant response was obtained that was potentiated by physostigmine and abolished by tetrodotoxin. The maximum response approximately equaled that of acetylcholine in a maximum concentration. In most bladder preparations from patients without known functional bladder disturbances, atropine (0.01 to 0.1 microM) had a marked inhibitory effect, and at concentrations exceeding 1 microM the blockade was complete. In strips obtained from patients undergoing transvesical prostatectomy, and who also had a cystometrically verified unstable bladder, there was a varying degree of atropine resistance, with some preparations showing a 50 per cent resistance to atropine. Prazosin, phentolamine, yohimbine, guanethidine, clonidine, and noradrenaline had no consistent effects on the electrically induced bladder contraction. Nifedipine and nimodipine caused a maximum of 65 per cent inhibition of the response. Addition of nimodipine to atropine-resistant strips when maximum atropine inhibition had been reached abolished the contractions. Omitting calcium from the bath solution rapidly abolished the electrically induced contraction. It is suggested that in the normal human bladder the contraction induced by electrical stimulation is mainly atropine sensitive. However, in the functionally disturbed bladder, part of the bladder contraction is atropine resistant, a finding that may have clinical implications.

Efficacy of desmopressin in the treatment of nocturia: a double‐blind placebo‐controlled study in men

Objective To investigate the efficacy and safety of oral desmopressin in the treatment of nocturia in men.

Changes in Contractile Properties in Hypertrophic Rat Urinary Bladder

Hypertrophy was induced in female rat urinary bladders by partial obstruction of the urethra. After 6 weeks the bladder weight had increased almost 7-fold compared to the matched controls. At this stage the animals were anesthetized and the pelvic nerves stimulated bilaterally at different bladder volumes. Isovolumetric pressures were measured by means of a catheter inserted via the urethra. For control (C) bladders maximum active pressure (104 +/- 11 cm. H2O, n = 5) was attained with 0.10 ml. content. For volumes above this a rapid progressive decrease in active pressure was noted. For hypertrophic (H) bladders maximum active pressure (92 +/- 14 cm. H2O, n = 6) was reached at 0.50 ml. Further filling decreased active pressure only slightly. By use of the law of Laplace the volume-active pressure relations were transformed to radius-force curves. The maximum active stress was similar for C and H bladders. The radius-force relation for H bladders was shifted to the right compared to the C curve (optimum radius for active force: C: 0.4 cm., H: greater than 0.9 cm.). This shift, responsible for the decreased ability to pressure production of the H bladders at small volumes indicates a dramatic remodelling of the smooth muscle in the hypertrophic bladder wall.

Smooth Muscle Cell Hypertrophy and Hyperplasia in the Rat Detrusor after Short-Time Infravesical Outflow Obstruction

Infravesical outflow obstruction of a duration of 3 days, 10 days and 6 weeks was induced in female rats by a standardized degree of urethral obstruction. A striking ability of the detrusor to respond to an acute obstruction with both smooth muscle cell hypertrophy and hyperplasia leading to an approximately 10-fold increase of the total muscle mass of the bladder wall after 6 weeks of obstruction was found. The maximum relative growth rate was greatest in the bladders subjected to obstruction for only 3 days, and this was also reflected by the concentrations of ornithine decarboxylase and the polyamines spermidine and spermine. The total amount of DNA in the detrusor was already significantly increased after 3 days, while a 9-fold increase was observed in the group subjected to obstruction for 6 weeks. At this time the smooth muscle cell nucleus volume also showed a considerable increase, and a comparison of the nucleus density and the DNA concentration suggested an increased mean DNA content per muscle cell nucleus. The concentration of RNA in the detrusor had already increased significantly after 3 days and also remained so after 10 days and 6 weeks of obstruction, a finding that coincided with the abundant appearance of nucleoli seen at electron microscopic investigation. The previously reported decreased ability to pressure production at small volumes in the rat urinary bladder subjected to an acute infravesical outflow obstruction might thus, at least in part, be due to changed contractile properties of the hypertrophic cells, and/or to an inefficient incorporation of the newly formed smooth muscle cells.

Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro

1 The present study was performed to investigate how blockade of the l‐arginine/nitric oxide (NO) pathway influences the function of the lower urinary tract in vivo, as studied by cystometry in conscious rats and in vitro, in isolated muscle preparations from the rat detrusor and urethra. 2 l‐NG‐nitro arginine methyl ester (l‐NAME), 10 and 20 mg kg−1, administered intra‐arterially, decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions. d‐NAME (20 mg kg−1) had no effect. No changes in the urodynamic parameters were recorded if l‐NAME (20 mg kg−1) was administered in combination with l‐arginine (200 mg kg−1). 3 Cystometries performed after intra‐arterial administration of sodium nitroprusside (SNP) (3 mg kg−1) and 3‐morpholino‐sydnonimin hydrochloride (SIN‐1, 2 mg kg−1) showed a decrease in bladder capacity, micturition volume and threshold pressure. SIN‐1, but not SNP, induced spontaneous bladder contractions. 4 Isolated precontracted urethral preparations responded to electrical stimulation with a frequency‐dependent tetrodotoxin‐sensitive relaxation. l‐NAME (10−4 m), but not d‐NAME, reduced the maximal relaxation to 31 ± 8% (n = 8) of the response prior to drug administration. The inhibition induced by l‐NAME was completely reversed by l‐arginine (10−3 m). SNP (10−8−10−4 m), SIN‐1 (10−6−3 × 10−4 m) and NO (10−5−10−3 m; present in acidified solution of NaNO2), caused relaxation (93–100%) of urethral preparations. l‐NAME did not affect these relaxations. 5 Detrusor strips contracted by carbachol or K+ showed contractions in response to electrical stimulation, even when pretreated with α,β‐methylene ATP and/or atropine. Small relaxations (14–41%) of detrusor strips were evoked by SNP (10−6−10−4 m), SIN‐1 (10−5−3 × 10−4 m) and NO (10−5−10−3 m). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition of l‐NAME (10−6−10−4 m) or l‐arginine (10−3 m). 6 The present results suggest that the l‐arginine/NO pathway is of functional importance for the bladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site of action of l‐NAME for inducing bladder hyperactivity in the rat is the outlet region rather than the detrusor muscle.

The standardization of terminology in nocturia: report from the standardization subcommittee of the International Continence Society

P. VAN KER REBROECK 1 , P. ABRAMS 2 , D. CHAIKIN 3 , J. DONOVAN 4 , D. FONDA 5 , S. JACKSON 6 , P. JENNUM 7 , T. JOHNSON 8 , G.R. LOSE 9 , A. MATTIASSON 10 , G.L. ROBER TSON 11 and J. WEISS 12 1 Chairman of the International Continence Society Standardization Committee, Department of Urology, University Hospital Maastricht, the Netherlands, 2 Bristol Urological Institute, Southmead Hospital, Bristol, UK, 3 Morristown Memorial Hospital, Morristown NJ, and Department of Urology, Weill Medical College of Cornell University, USA, 4 Department of Social Medicine, University of Bristol, Bristol, UK, 5 Aged Care Services, Caulfield General Medical Centre, Victoria, Australia, 6 Department of Gynaecology, John Radcliffe Hospital, Oxford, UK, 7 Department of Clinical Neurophysiology, University of Copenhagen and Sleep Laboratory, Glostrup, Denmark, 8 Rehabilitation Research and Development Center, Atlanta VA Medical Centre, Georgia, USA, 9 Department of Obstetrics and Gynaecology, Glostrup County Hospital, University of Copenhagen, Denmark, 10 Department of Urology, Lund University Hospital, Lund, Sweden, 11 Northwestern University Medical School, Chicago, USA, 12 Department of Urology, Weill Medical College of Cornell University and The New York Presbyterian Hospital, New York, NY, USA

Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of a new, once‐daily extended‐release (ER) formulation of tolterodine in treating overactive bladder in older (≥65) and younger (<65) patients.

Origin and distribution of neuropeptide Y-, vasoactive intestinal polypeptide- and substance P-containing nerve fibers in the urinary bladder of the rat

SummaryThe origin and distribution in the urinary bladder of nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and substance P (SP) were investigated in rats. Experimental procedures comprised preganglionic decentralization or postganglionic denervation of the bladder and also chemical sympathectomy as well as capsaicin treatment of newborn rats.Nerve fibers containing NPY were richly distributed in the detrusor muscle and also in the pelvic ganglia. Numerous NPY-containing nerve cell bodies were found in pelvic ganglia. A rich occurrence of VIP fibers and a more sparse distribution of SP-containing fibers were also found in the bladder as well as a relatively rich representation of VIP- containing nerve cell bodies in the pelvic ganglia. After decentralization the intensity of VIP and NPY immunofluorescence increased in nerve cell bodies of the pelvic ganglia and in nerve fibers in the wall of the bladder. Postganglionic denervation, on the other hand, eliminated all peptides examined in the bladder wall. After postganglionic denervation the situation in the ganglia was approximately the same as after decentralization. Chemical sympathectomy (6-OHDA) did not seem to change significantly the frequency and distribution of VIP-, SP- and NPY-fibers in the muscle layer of the bladder or in the pelvic ganglia, while the NPY-containing nerve fibers in the submucosal layer and around blood vessels of the bladder disappeared. Adrenergic nerve fibers in the wall of the bladder (visualized by histofluorescence) were markedly reduced in number after administration of 6-OHDA. Capsaicin-treatment of newborn rats caused a loss of SP-fibers in the wall of the bladder, supporting the view that these fibers are sensory in nature in the urinary bladder. Although it cannot be entirely excluded that NPY-containing fibers in the wall of the bladder are adrenergic, the present results suggest that the NPY-fibers as well as the VIP-fibers of the bladder wall originate mainly in non-adrenergic cell bodies of the pelvic ganglia. However, perivascular NPY-containing nerve fibers are adrenergic in nature.

Prostaglandin E sub 2 −Induced Bladder Hyperactivity in Normal, Conscious Rats: Involvement of Tachykinins?

In normal conscious rats investigated by continuous cystometry, intravesically instilled prostaglandin (PG) E2 facilitated micturition and increased basal intravesical pressure. The effect was attenuated by both the NK1 receptor selective antagonist RP 67,580 and the NK2 receptor selective antagonist SR 48,968, given intra-arterially, suggesting that it was mediated by stimulation of both NK1 and NK2 receptors. Intra-arterially given PGE2 produced a distinct increase in bladder pressure before initiating a micturition reflex, indicating that the PG had a direct contractant effect on the detrusor smooth muscle. The effect of intra-arterial PGE2 could not be blocked by intra-arterial RP 67,580 or SR 48,968, which opens the possibility that the micturition reflex elicited by intra-arterial PGE2 was mediated by pathways other than the reflex initiated when the PG was given intravesically. The present results thus suggest that intra-arterial PGE2, given near the bladder, may initiate micturition in the normal rat chiefly by directly contracting the smooth muscle of the detrusor. However, when given intravesically, PGE2 may stimulate micturition by releasing tachykinins from nerves in and/or immediately below the urothelium. These tachykinins, in turn, initiate a micturition reflex by stimulating NK1 and NK2 receptors. Prostanoids may, via release of tachykinins, contribute to both urge and bladder hyperactivity seen in inflammatory conditions of the lower urinary tract.