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Biomedical subjects

A Mattiasson

Publications and source records attributed to A Mattiasson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Distribution of neuropeptide-, tyrosine hydroxylase- and nitric oxide synthase containing nerve fibers in the external urethral sphincter of the rat.

The occurrence and distribution of adrenergic, peptidergic and nitrergic nerve fibers were investigated within the part of the rat urethra that corresponds to the external urethral sphincteric mechanism. At this level, the urethral wall was found to be composed of the following layers: mucosa/urothelium, lamina propria, smooth muscle, mixed smooth and striated muscle and striated muscle. Nerve fibers containing immunoreactivity against either nitric oxide synthase (NOS) or any of the following peptides were visualised in various amounts in all three muscle layers of rats of both sexes: neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), cholecystokinin (CCK), gastrin releasing peptide (GRP) and pituitary adenylate cyclase-activating peptide. (PACAP) Tyrosine hydroxylase (TH), marker for nonadrenergic nerves, was only found in nerve fibers of the smooth and mixed muscle layers, while enkephalin 8 (ENK-8) was only found in the striated muscle layer. The great number of putative neuromessengers and different nerve fiber populations suggest a complex innervation pattern of the sphincter area.

Animals↗
PubMed1995

Urodynamic and other effects of tolterodine: a novel antimuscarinic drug for the treatment of detrusor overactivity.

Tolterodine, a novel compound intended for treatment of urgency and urge incontinence, has been characterized as a potent muscarinic receptor antagonist in pharmacological in vitro and in vivo studies. In cats, tolerodine was shown to reduce bladder pressure at doses significantly lower than those affecting salivation. To predict clinical effectiveness, an open pilot study was performed in healthy male volunteers. Efficacy was measured by cystometry and by spontaneously reported effects after administration of a single oral dose of tolterodine, 6.4 mg, given as a water solution. Tolterodine had distinct inhibitory effects on urinary bladder function, both at 1 and 5 hours post-dose. At 1 hour, but not at 5 hours post-dose tolterodine also significantly reduced stimulated salvation. In addition to the objectively demonstrated changes in urodynamic parameters, most volunteers experienced voiding difficulties. No significant changes in blood pressure, heart rate, or near point of accommodation were registered. Tolterodine, in the dosage used, was both objectively and subjectively shown to exert a marked inhibitory effect on micturition in healthy subjects, and the data suggest a more pronounced effect on bladder function than on salivation.

Adult↗
PubMed1995

Facilitatory effect of pituitary adenylate cyclase activating polypeptide on micturition in normal, conscious rats.

In unanaesthetized, normal rats, continuous cystometry revealed that pituitary adenylate cyclase activating peptide (PACAP-27), administered intrathecally or intra-arterially near the bladder, stimulated micturition. The localization of PACAP-27 in the rat lower urinary tract was studied by immunohistochemistry, and the direct effects on the smooth muscles of the rat detrusor and urethra were investigated in vitro. In the intact rat, 1.0 nmol of PACAP-27 administered intrathecally as well as intra-arterially close to the bladder, but not intravenously, increased micturition pressure, decreased micturition volume and bladder capacity, and facilitated spontaneous bladder contractions. PACAP-27 immunoreactive structures were extremely scarce in the lower urinary tract, and the peptide had negligible effects on isolated detrusor muscle contracted by carbachol or stimulated electrically, or on urethral preparations contracted by noradrenaline. These results suggest that PACAP-27 has facilitatory actions on micturition both at the spinal cord and peripheral ganglionic levels.

Animals↗
PubMed1995

Prostaglandin E2-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.

Administration, Intravesical↗
PubMed1995

Urodynamic effects of intravesical resiniferatoxin and capsaicin in conscious rats with and without outflow obstruction.

PURPOSE: The urodynamic effects of intravesical resiniferatoxin and capsaicin were investigated in rats. MATERIALS AND METHODS: Continuous cystometry was performed in conscious, female Sprague-Dawley rats with and without outflow obstruction. RESULTS: Intravesical instillation of resiniferatoxin facilitated micturition. The potency of the drug was approximately 1,000 times higher than that of capsaicin. Repeated instillations of resiniferatoxin for 6 consecutive days caused desensitization to resiniferatoxin. This was not found with repeated instillations of capsaicin. Capsaicin was also effective in rats with bladder hypertrophy, while resiniferatoxin was not. CONCLUSIONS: The findings suggest that resiniferatoxin can induce desensitization of vanilloid receptor-mediated release of tachykinins in the rat urinary bladder and that intravesical resiniferatoxin would be an interesting alternative to intravesical capsaicin in the treatment of selected cases of bladder hypersensitivity/hyperactivity.

Administration, Intravesical↗
PubMed1995

Tachykinin effects on bladder activity in conscious normal rats.

When instilled intravesically in normal, unanesthetized rats, neurokinin A (NKA), but not substance P (SP) and neurokinin B (NKB), stimulated micturition. The effect of NKA was inhibited by the NK2 receptor selective antagonists SR 48,968 and MEN 10,627, but not by the NK1 receptor selective antagonist RP 67,580, suggesting that the effect was mediated by stimulation of NK2 receptors. Given intra-arterially near the bladder, NKA produced an increase in basal intravesical pressure before initiating micturition, indicating that the tachykinin had a direct contractant effect on the detrusor smooth muscle. Such a contractile effect was not observed when NKA was given intravesically. The effect of intra-arterial NKA could not be blocked by the NK1 receptor selective antagonist SR 140,333 or the NK2 receptor selective antagonist SR 48,968, but by their combination. Also intra-arterial NKB stimulated micturition, but was less potent than NKA. Intra-arterial SP had only weak stimulating effects. The results suggest that intravesically administered NKA can initiate micturition in the normal rat by stimulation of superficially located NK2 receptors in the urothelium. Intra-arterially administered NKA caused bladder hyperactivity via stimulation of both NK1 and NK2 receptors.

Administration, Intravesical↗
PubMed1995

Effects of neurokinin receptor antagonists on L-dopa induced bladder hyperactivity in normal conscious rats.

PURPOSE: The urodynamic effects of intrathecal neurokinin (NK) receptor blockade on L-dopa-induced bladder hyperactivity were investigated in a rat model. MATERIALS AND METHODS: Continuous cystometry was performed in normal, conscious, female Sprague-Dawley rats. RESULTS: In rats pretreated with intraperitoneal carbidopa 50 mg./kg., intraperitoneal L-dopa 50 mg./kg. caused bladder hyperactivity that could be attenuated by intrathecal administration of the NK1 receptor selective antagonist SR 140,333 (2 nmol.), whereas the NK2 receptor selective antagonist SR 48,968 (2 nmol.) failed to do so. Combination of SR 140,333 (2 nmol.) and SR 48,968 (2 nmol.), which by itself decreased micturition pressure, practically abolished the L-dopa-induced hyperactivity. CONCLUSIONS: The present results suggest that tachykinins, via stimulation of NK1 (and/or NK2) receptors, are involved in L-dopa-induced bladder hyperactivity, most probably at the spinal level. This implies tachykinin involvement in the supraspinal pathways that control the sacral parasympathetic center innervating the urinary bladder. It also implies that spinal NK receptors are a possible target for drugs aimed for elimination of bladder hyperactivity mediated via these pathways.

Animals↗
PubMed1994

Capsaicin-induced bladder hyperactivity in normal conscious rats.

Capsaicin, instilled intravesically in normal, unanesthetized rats induced a concentration-dependent bladder hyperactivity, which could be abolished by hexamethonium, given intra-arterially near the bladder, or by morphine administered intrathecally. The effect was reversible and could be repeated. The NK-2 receptor selective antagonist SR 48,968 and the nonselective NK receptor antagonist spantide, given intra-arterially near the bladder, which by themselves, in the concentrations used, did not affect cystometric parameters, both counteracted the capsaicin-induced hyperactivity, whereas the NK-1 receptor selective antagonist RP 67,580 failed to do so. Blockade of tachykinin receptors in the urinary bladder does not seem to produce changes of the micturition reflex associated with bladder filling in the conscious rat. However, tachykinins released from capsaicin-sensitive nerves by various stimuli may, through stimulation of NK-2 receptors, lower the threshold for initiation of the micturition reflex. In the rat, intravesical capsaicin may be a suitable model for studies of afferent activity caused by stimuli releasing peptides from sensory nerves in the bladder, thereby provoking bladder hyperactivity.

Administration, Intravesical↗
PubMed1994

Micturition and premicturition contractions in unanesthetized rats with bladder outlet obstruction.

The cholinergic and purinergic neurotransmission involved in micturition contraction and premicturition contractile activity (bladder hyperactivity) were investigated by continuous cystometry in unanesthetized rats with outlet obstruction. Adenosine triphosphate (ATP), administered intra-arterially close to the bladder, produced rapid, phasic dose-dependent increases in bladder pressure and micturition immediately after the injections. The percentage volume expelled was 74 +/- 9% after 5 mg/kg. Intra-arterial alpha,beta-methylene ATP also produced a rapid, phasic increase in bladder pressure and micturition immediately after the injection. The percentage volume expelled was 96 +/- 3% after 1 mg./kg; the residual volume of the following voidings increased, and the micturition pressure tended to decrease. However, dribbling incontinence was not produced. The amplitude of the premicturition contractions decreased significantly (p < 0.01) after the administration. Intra-arterial carbachol produced rapid, longlasting dose-dependent increases in bladder pressure and micturition. The percentage volume expelled was 88 +/- 4 after 5 micrograms./kg. Bladder capacity and micturition volume decreased significantly (p < 0.05) during the following spontaneous voidings. Intra-arterial atropine (1 mg./kg.) increased bladder capacity (p < 0.01) and residual volume (p < 0.01), and tended to decrease micturition pressure (by 25%) and micturition volume. However, micturition contractions still remained after the injection, even if they changed appearance, and were of shorter duration. Atropine had no effect on the premicturition contractions. In the presence of atropine, alpha,beta-methylene ATP initially produced a rapid, phasic increase in bladder pressure with micturition. Then, dribbling incontinence was observed in 1 of 5 animals. Hexamethonium, administered intra-arterially in doses producing urinary retention and dribbling incontinence (20 or 40 mg./kg.), increased the amplitude of the premicturition contractions, but decreased the frequency of the contractions. Intra-arterial tetrodotoxin (15 micrograms./kg.) inhibited micturition, and produced dribbling incontinence in all animals tested (n = 6). However, the amplitude of the premicturition contractions was not suppressed. Intra-arterial (+/-)-pinacidil (0.2 mg./kg.) significantly (p < 0.05) decreased both amplitude and frequency of these contractions. It is concluded that both cholinergic and purinergic transmission seem to be of importance for pressure generation and emptying of the bladder in rats with outlet obstruction. The present results also give further support for the view that the premicturition contractions seen in these animals are of myogenic origin.

Adenosine Triphosphate↗
PubMed1994

Role of intrathecal tachykinins for micturition in unanaesthetized rats with and without bladder outlet obstruction.

1. The effects on micturition of RP 67,580, a selective NK1 receptor antagonist, and SR 48,968, a highly, potent antagonist at NK2 receptor sites, given intrathecally (i.t.) or intra-arterially (i.a.) near the bladder, were investigated in unanaesthetized rats with and without bladder outlet obstruction. 2. In normal rats, RP 67,580, given i.t. in doses of 2 and 20 nmol per rat, decreased micturition pressure, but did not change other cystometric parameters. After 20 nmol of RP 67,580, dribbling incontinence due to retention was observed in 1 out of 7 animals. This effect was reversible. I.t. RP 67,580 in a dose of 2 nmol, had no effect on hyperactivity induced by intravesically instilled capsaicin. 3. In animals with bladder hypertrophy secondary to outflow obstruction, RP 67,580, given i.t. in a dose of 2 nmol per rat, decreased the micturition pressure, but had no effect on other cystometric parameters. After 20 nmol, dribbling incontinence due to retention was observed in 5 out of 7 animals. 4. RP 67,580, given i.a. in a dose of 4 nmol, had little effect on the cystometric parameters investigated, both in normal animals and rats with bladder hypertrophy. 5. SR 48,968, given i.t. in doses of 2 and 20 nmol per rat, had no clear-cut effects on the micturition pattern in normal rats, or rats with bladder hypertrophy. However, the drug reduced capsaicin-induced bladder hyperactivity. When given i.a. in a dose of 4 nmol, SR 48,968 had no effect on cystometric parameters in normal rats or rats with bladder hypertrophy. 6. The effects of both RP 67,580 and SR 48,968 were stereoselective, their enantiomers (RP 68,651 and SR 48,965) being inactive.7. These results thus suggest that at the spinal level there is a tachykinin involvement (via NK,receptors) in the micturition reflex induced by bladder filling, both in normal rats, and, more clearly, in animals with bladder hypertrophy secondary to outflow obstruction. The bladder response to filling was not influenced by blockade of vesical NKI and NK2 receptors. On the other hand, the bladder hyperactivity evoked by intravesical capsaicin seems to involve NK2 receptors both at the bladder and spinal levels.

Analgesics↗
PubMed1994

Circumvaginal surface electromyography in women with urinary incontinence and in healthy volunteers.

In this study we developed a probe for surface EMG investigation of the circumvaginal muscle function in women with various forms of urinary incontinence. 69 women were investigated, 20 healthy volunteers, 25 patients with stress incontinence, 11 with urge incontinence and 13 with a mixed type of incontinence. We found that the circumvaginal surface EMG activity at short lasting (2 sec) maximum contraction was significant lower in patients with incontinence compared to healthy volunteers. We also found that the ability to hold a maximum contraction during one minute was significant reduced in all the patient groups compared to controls. The results suggest that patients with stress, urge or mixed incontinence all seem to have a defective function of the circumvaginal musculature. A common aetiology for stress, urge and mixed incontinence seems to be a reasonable working hypothesis for future investigations.

Adult↗
PubMed1993

A rat model for investigation of spinal mechanisms in detrusor instability associated with infravesical outflow obstruction.

A rat model of infravesical outflow obstruction was modified to allow cystometric investigation in conscious, free-moving animals after intrathecal drug administration. The catheter position and extent of drug distribution were controlled by injection of dye and dissection of the spinal canal. Continuous cystometries were performed in awake normal rats as well as rats with bladder hypertrophy and hyperactivity following infravesical outflow obstruction. In some animals of each group, cystometry was performed with simultaneous recording of intra-abdominal pressure. The possible effects of the presence of the intrathecal catheter were studied, as well as the effects of saline, local anesthetics, morphine and naloxone administered through the catheter. Neither the presence of the intrathecal catheter nor injection of saline affected the cystometric pattern. Bupivacaine (50 micrograms) produced paralysis of both lower extremities and a complete, though reversible, suppression of micturition in normal rats. In rats with hypertrophy, intrathecal bupivacaine in doses of 50 micrograms and 100 micrograms produced decreases in micturition pressure, increases in bladder capacity and dribbling incontinence. However, the amplitude of spontaneous contractile activity increased after the administration. The inhibitory effects of morphine (0.5-10 micrograms) on micturition in normal rats, which were rapidly reversed by naloxone, were in accordance with results obtained in previous studies in anesthetized animals. Rats with bladder hypertrophy showed a similar response to morphine and naloxone. However, the bladder hyperactivity was not inhibited by morphine. We conclude that the present model seems reliable for the study of spinal mechanisms in the development of detrusor instability associated with infravesical outflow obstruction.

Animals↗
PubMed1993

Effects of GABA-receptor stimulation and blockade on micturition in normal rats and rats with bladder outflow obstruction.

The effects on micturition of the GABA receptor agonists muscimol (selective for GABAA-receptors) and baclofen (selective for GABAB-receptors), given intrathecally and intra-arterially to unanesthetized rats with and without bladder hypertrophy secondary to outflow obstruction, were studied by continuous cystometry. When given intrathecally in increasing doses, both muscimol (1 to 10 micrograms) and baclofen (0.1 to 5 micrograms) produced a dose-dependent inhibition of micturition with progressive increases in bladder capacity and residual volume, and a decrease in micturition pressure ending with urinary retention and dribbling incontinence. Generally, the effects were similar in normal rats and rats with bladder hypertrophy. In normal rats, bicuculline (blocking GABAA-receptors) decreased bladder capacity and micturition volume, and increased micturition pressure. In both types of rat, the effects of muscimol and baclofen were partly counteracted by bicuculline and baclofen, respectively. In rats with bladder hypertrophy, the amplitude of the spontaneous bladder contractions during filling was significantly increased after administration of muscimol and baclofen. When given intra-arterially in high doses, muscimol (2 to 16 mg./kg.) and baclofen (8 to 16 mg./kg.) produced effects on cystometric parameters and spontaneous bladder contractions similar to those obtained with intrathecal administration. These results suggest that muscimol and baclofen have insignificant peripheral effects on the lower urinary tract, but depress micturition by an effect on the central nervous system. They also suggest that the inhibitory GABA-ergic system does not play a role in the genesis of bladder hyperactivity in rats with outflow obstruction.

Animals↗
PubMed1993

Intravesical instillation of terodiline--an in vivo study of drug absorption in rabbit and man.

The absorption of intravesically administered terodiline was investigated in 8 healthy volunteers (10(-4)) and in 33 rabbits (10(-4)) M., 4 X 10(-4) M. and 1.6 X 10(-3) M.). In the humans, the amount of drug retained and the serum concentration were registered. In the rabbits, the influence of drug concentration, pH (5 and 9.2) and volume (5 and 20 ml.) were evaluated. Liquid scintigraphy of the bladder wall and of serum and tissue samples from striated muscle, kidney and liver was performed. Further, autoradiography of the bladder wall and calculation of drug retention were done. In the humans, 20 +/- 5% of the administered terodiline dose was retained in the body. Clinically significant serum concentrations were not detected. In the rabbits, 21 +/- 4% of the drug was retained with the pH = 5 terodiline solution as compared with 64 +/- 3% with the pH = 9.2 solution. With increasing terodiline concentrations, drug retention increased, as did the tissue and serum activities. At a given concentration, the total amount of drug retained increased with a larger volume. The drug gradient between the bladder muscle layer and serum was of a magnitude of about 100, independent of the drug concentration within the muscle layer. It is concluded that the pH and concentration of the solution are factors of major importance for the amount of terodiline absorbed from the bladder. Compared with the one obtainable by systemic drug administration, the large gradient between the bladder muscle and the serum is conspicuous, and may be of clinical interest.

Administration, Intravesical↗
PubMed1993

Urodynamic effects of intravesical instillation of atropine and phentolamine in patients with detrusor hyperactivity.

The effects of intravesical instillation of atropine (10(-6) M) and phentolamine (10(-6) M) on urodynamic parameters were investigated in patients with detrusor hyperactivity of neurogenic or non-neurogenic origin. A modified cystometric technique with slow intermittent filling was used. The reproducibility of the investigative procedure was first verified in 17 patients. Eighteen patients, 12 with detrusor hyperreflexia and 6 with detrusor instability, were then investigated with atropine and 17 patients, 11 with detrusor hyperreflexia and 6 with detrusor instability, were investigated with phentolamine. In individual patients clinically relevant improvements, such as an increased bladder capacity and a decreased detrusor pressure, were found. Five/12 neurogenic and 1/6 non-neurogenic patients responded to instillation of atropine. Five/11 neurogenic but none of the non-neurogenic patients responded to phentolamine. In the neurogenic group phentolamine caused an increase of the bladder capacity from 247 +/- 57 ml. to 378 +/- 57 ml. (p < 0.05). It is suggested that the different sensitivities to intravesical drug administration in patients with detrusor hyperreflexia and detrusor instability can be explained by pathophysiological differences and concluded that intravesical instillation of drugs may be of therapeutic value in selected groups of patients.

Administration, Intravesical↗
PubMed1993

Facilitatory effect of vasoactive intestinal polypeptide on spinal and peripheral micturition reflex pathways in conscious rats with and without detrusor instability.

In unanesthetized, normal rats, and rats with bladder hypertrophy following infravesical outflow obstruction, cystometry was performed to investigate the effects of spinal and peripheral administration of vasoactive intestinal polypeptide (VIP) on micturition. In addition, the direct effects of the peptide on isolated smooth muscle preparations of detrusor and urethra were studied. In normal animals, 10 micrograms. of VIP administered intrathecally as well as intra-arterially close to the bladder, but not intravenously, decreased micturition volume and bladder capacity, and facilitated spontaneous bladder contractions. In animals with bladder hypertrophy, the same dose of VIP intrathecally had similar effects on these three parameters, but the effects of VIP given intra-arterially were less pronounced. VIP given intravenously was ineffective. Hexamethonium 5 mg. x kg.-1 given intraarterially did not block the stimulatory effect of VIP 10 micrograms. given intra-arterially to normal animals. VIP had negligible effects on isolated detrusor muscle contracted by carbachol or electrical stimulation, or on urethral preparations contracted by noradrenaline. These results suggest that VIP has a facilitatory action on the micturition reflex at the spinal cord and ganglionic levels.

Animals↗
PubMed1993

Functional importance of cholinergic and purinergic neurotransmission for micturition contraction in the normal, unanaesthetized rat.

1. The cholinergic and purinergic neurotransmission involved in micturition in the normal, unanaesthetized rat was investigated by means of continuous cystometry. 2. ATP (1 and 5 mg kg-1), administered intra-arterially (i.a.) close to the bladder, produced rapid, phasic, dose-dependent increases in bladder pressure with micturition immediately after injection. The micturition pressure of the following spontaneous voidings increased, and bladder capacity, micturition volume, and residual volume decreased. Pretreatment with alpha,beta-methylene ATP (1 mg kg-1, i.a.) blocked the effects of ATP (5 mg kg-1). 3. alpha,beta-Methylene ATP (0.25, 0.5 and 1 mg kg-1, i.a.) produced rapid, phasic, increases in bladder pressure with micturition immediately after injection. The effects of alpha,beta-methylene ATP (0.25 mg kg-1, i.a.) were not affected by pretreatment with indomethacin (0.5-2 mg kg-1, i.a.). The micturition pressure of the subsequent spontaneous voidings decreased, and bladder capacity and residual volume increased. 4. Carbachol (5-50 micrograms kg-1, i.a.) produced rapid, sustained, dose-dependent increases in bladder pressure with micturition, and then increased basal pressure, threshold pressure, and micturition pressure, and decreased bladder capacity and micturition volume during the following spontaneous voidings. 5. Atropine (1 mg kg-1, i.a.) decreased micturition pressure and micturition volume, but did not induce dribbling incontinence. Micturition contractions still occurred after the injection, but changed in appearance and were of shorter duration than before. In the presence of atropine (1 mg kg-1, i.a.), alpha,beta-methylene ATP (1 mg kg-1, i.a.) produced initially a phasic increase in bladder pressure with micturition and then dribbling incontinence in all animals tested. 6. After blockade of the micturition reflex with morphine (10 microg intrathecally), ATP (5 mg kg-1, i.a.),alpha,beta-methylene ATP (0.25-1 mg kg-1 , i.a.), and carbachol (5-500 microg kg-1, i.a.) were unable to empty the bladder.7. The results suggest that drug-induced bladder emptying in the normal, unanaesthetized rat requires an intact micturition reflex and they support the view that the two physiologically important transmitters involved in micturition are acetylcholine and ATP.

Adenosine Triphosphate↗