Biomedical subjects

A Mattiasson

Publications and source records attributed to A Mattiasson.

At least 91 records · Page 5Linked to original sources

PubMed1987

Bladder vasodilatation and release of vasoactive intestinal polypeptide from the urinary bladder of the cat in response to pelvic nerve stimulation.

In the feline urinary bladder blood flow was determined by means of a direct blood flow measurement technique before and during pelvic nerve stimulation. Simultaneous sampling of venous blood from the bladder was performed, and the output of vasoactive intestinal polypeptide (VIP) was determined by means of radioimmunoassay. Maximal stimulation of the pelvic nerves led to a clearcut increase in intravesical pressure and a small but sustained increase of blood flow in the bladder wall. These changes were associated with a drastic increase in VIP output from the bladder, increasing from a control level of 0.2 fmol./min. to 15 fmol./min. during stimulation. The results suggest that VIP might be the neurotransmitter responsible for the vasodilatation in the feline urinary bladder in response to pelvic nerve stimulation. The discrepancy between the moderate blood flow increase and the pronounced increase in VIP-release might, however, indicate that VIP exerts its main effects elsewhere in the bladder than in the vascular bed, for instance the detrusor smooth muscle.

Animals↗

PubMed1987

Ketanserin interaction with urethral alpha-adrenoceptors.

The selective 5-HT2 receptor blocker ketanserin was found to reduce maximal urethral pressures in healthy females by about 40% without reducing blood pressure. In vitro, ketanserin completely or almost completely reduced contractions of the isolated female rabbit urethra induced by phenylephrine, noradrenaline (NA) and electrical field stimulation. The drug was less effective against responses evoked by clonidine and 5-hydroxytryptamine (5-HT). 5-HT-induced contractions were effectively reduced by methysergide, but little affected by prazosin and rauwolscine. In concentrations exceeding 10(-7) M ketanserin significantly increased efflux of 3H in 3H-NA preloaded preparations of rabbit urethral muscle. Low concentrations of 5-HT, less than 10(-6) M, had slight inhibitory effects of 3H release, whereas 5-HT 10(-5) M caused a significant increase. It is concluded that ketanserin counteracts the effects of postjunctional alpha 1-adrenoceptor stimulation in isolated rabbit urethra. Such an effect might also explain its urethral pressure lowering action in man.

Adult↗

PubMed1987

Interaction between adrenergic and cholinergic nerve terminals in the urinary bladder of rabbit, cat and man.

The influence of muscarinic receptor stimulation (carbachol) and blockade (scopolamine) on the release of 3H-labelled noradrenaline from adrenergic neurons was investigated in isolated detrusor preparations from rabbit, cat and man. A significant influence on the release of 3H from adrenergic nerve terminals was found in the three species with a concentration-dependent decrease and increase induced by carbachol and scopolamine, respectively. Using the alpha 2-adrenoceptor stimulating and blocking agents clonidine and rauwolscine in rabbit and human detrusor preparations, the presence of prejunctionally located inhibitory alpha 2-adrenoceptors could also be demonstrated. The findings indicate the possibility of a functionally important interaction between cholinergic and adrenergic nerves in the urinary bladder mediated via inhibitory muscarinic receptors on adrenergic nerve terminals.

Animals↗

PubMed1987

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.

Anesthesia, General↗

PubMed1986

Contelle: pelvic floor stimulator for female stress-urge incontinence. A multicenter study.

The clinical efficacy of a new device for treatment of female incontinence was studied in a multicenter trial. The device consists of an inflatable electrode carrier and an external stimulator unit. Forty women were treated: 10 had primary or recurrent genuine stress incontinence, 15 had urge incontinence due to idiopathic detrusor instability, not responding to drug treatment, and 15 had stress incontinence combined with detrusor instability. Twenty-five patients were improved by the treatment. Another 8 reported an excellent result of treatment and remained free of symptoms for more than six months after withdrawal of the treatment. The results were more favorable in patients with bladder hyperactivity than in genuine stress incontinence. The patients' general ratings of treatment efficacy correlated well with their recordings of urinary frequency and consumption of incontinence pads. The functional bladder capacity increased in improved patients, but normalization of urodynamic parameters was no prerequisite for clinical improvement. We found intravaginal electrical stimulation to be a valuable alternative to medical and surgical intervention in patients with detrusor instability.

Adult↗

PubMed1986

Detrusor collagen content in the denervated rat urinary bladder.

Neurogenic bladder dysfunction was created in male rats by removal of the pelvic ganglia. The bladders were then emptied manually once daily, and kept free from infection. After 10 days or six weeks the bladders were taken out and the mucosa-submucosa was removed. The detrusors were then weighed and used for collagen assay. Detrusor weight increased 4.5 and six times after 10 days and six weeks, respectively. Total detrusor collagen increased 2.3 and 3.7 times, but due to the increase in detrusor weight the concentration decreased to 60 per cent of normal. The electron microscopic investigation showed that the cross-sectional area of the smooth muscle cells had increased fourfold after six weeks. The collagen fibrils were found mainly in the interstitial tissue between the muscle bundles. As these increased in size following the neurogenic lesion, the collagen-rich tissue component decreased relatively. Our conclusion is that frequent emptying and the avoidance of bladder infection protects the denervated rat urinary bladder wall from injuries that would otherwise lead to an increased collagen concentration.

Animals↗

PubMed1985

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

The 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Characterization of the muscarinic cholinoceptors in the human detrusor.

Contractions of the human detrusor are thought to be mediated mainly via cholinergic muscarinic receptors. In the present study, we used a receptor-binding technique with 1-quinuclidinyl[phenyl 4-3H]benzilate ((-)3H-QNB) as radioligand to directly demonstrate the presence of muscarinic receptors in homogenates of the human detrusor. The binding of (-)3H-QNB was of high affinity (KD = (1.2 +/- 0.1) X 10(-10) M), saturable (Ro = 160 +/- 15 fmol./mg. protein) and possessed the pharmacological specificity expected of an interaction with muscarinic receptors. Muscarinic receptor antagonists were bound to a virtually uniform population of sites, whereas muscarinic receptor agonists recognized more than one population of muscarinic binding sites. The affinities of a series of antimuscarinic drugs, determined in competition experiments with (-)3H-QNB, were found to correlate with the capacity to inhibit carbachol-induced contractions in isolated human bladder muscle. Binding data together with the functional data indicated that the human detrusor does not contain any significant number of muscarinic spare receptors. The results suggest that a selective effect on the muscarinic receptors of human bladder is not possible to obtain with presently available antimuscarinic agents.

Adult↗

PubMed1985

Changes in vascular resistance in the feline urinary bladder in response to bladder filling.

The effect of bladder filling on vesical blood flow was studied in anesthetized cats. The pelvic nerves were sectioned and the bladder venous outflow was recorded by a drop counter. Filling of the bladder induced a sustained increase in vesical blood flow, related to the bladder volume. Thus, injection of 10, 20 and 30 ml. of saline decreased bladder vascular resistance by 27, 47 and 52 per cent, respectively. This vasodilation occurred despite a steady state increase in bladder pressure by 25 to 50 cm. H2O. Upon emptying of the bladder, blood flow decreased towards control values. The response was unaffected by alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol) and muscarinic cholinoceptor blockade (atropine). The vasodilation was eliminated by papaverine, indicating that the response was not due to a rearrangement of the vessels at large bladder volumes. The vasodilation was not associated with any increase in the concentrations of vasoactive intestinal polypeptide (VIP) or substance P in the venous effluent blood. Indomethacin significantly reduced the vasodilatation induced by filling. We conclude that local mechanisms, possibly involving release of prostaglandins, are involved in the vasodilation following bladder distension.

Animals↗

PubMed1985

Effects of vasoactive intestinal polypeptide on isolated urethral and urinary bladder smooth muscle from rabbit and man.

Vasoactive intestinal polypeptide concentration-dependently inhibited the contractant responses of isolated preparations of the female rabbit bladder and urethra induced by electrical field stimulation and exogenous application of acetylcholine (bladder) and noradrenaline (urethra). The inhibition of alpha-adrenoceptor and muscarinic cholinoceptor-mediated activity in the urethra and bladder amounted to 50 to 90 per cent of induced contractions. The nonadrenergic noncholinergic contraction induced by electrical field stimulation in the urethra was reduced slightly, whereas corresponding response in the bladder was more sensitive. The maximum inhibition of both the electrically induced responses and contractions induced by exogenous noradrenaline and acetylcholine was of comparable size in the urethra and the bladder. The effects of vasoactive intestinal polypeptide seemed to be exerted postjunctionally since no significant influence of the peptide was seen on the release of 3H-noradrenaline from adrenergic nerve endings in the urethra. The effects of vasoactive intestinal polypeptide in human urethral and bladder preparations were less consistent. The noradrenaline-induced contraction in urethral preparations was inhibited by 29 +/- 9 per cent (no. = 22). The effects on electrically induced contractions in the urethra, and on responses to acetylcholine and electrical field stimulation in the bladder, were small and inconsistent. It is concluded that vasoactive intestinal polypeptide may be of importance for regulation of lower urinary tract smooth muscle activity in the rabbit. It cannot be excluded that the peptide has a modulatory role in neurotransmission in human urethral muscle. However, the present results do not support the view of vasoactive intestinal polypeptide as an inhibitor of contraction in human detrusor.

Acetylcholine↗

PubMed1985

Adrenergic and non-adrenergic contraction of isolated urethral muscle from rabbit and man.

Isolated urethral muscle from rabbit and man was subjected to electrical field stimulation and the components of the resulting contraction were analyzed. Contraction usually consisted of 2 main components. One was rapidly developing, non-adrenergic and atropine-resistant. The other developed more slowly and was sensitive to alpha-adrenoceptor blockade and to chemical sympathectomy with 6-hydroxydopamine. By lowering the temperature from 37C to 20C, these contraction components could be separated from each other. Both could be blocked by tetrodotoxin but the effects of this drug were not consistent in human tissue. Characteristic for the initial contraction component was its dependence on the tension of the preparation; it increased with increasing tension. The adrenergic part of the contraction could be effectively blocked by phentolamine and prazosin, whereas rauwolscine was less effective. Atropine and scopolamine also inhibited the adrenergic part of the contraction, whereas acetylcholine caused a transient increase. The non-adrenergic contraction component was less sensitive to deprivation of extracellular Ca2+ than the adrenergic; almost 40 per cent remained after exposure to Ca2+ free solution for 40 min., whereas the adrenergic component disappeared after 20 min. exposure. Light and electron microscopic investigation revealed 3 distinct layers of the rabbit urethral wall, 1 outer consisting of smooth and striated muscle, 1 middle consisting of smooth muscle only, and a submucosal layer where vessels and smooth muscle cells were found. Removal of the longitudinal muscle layer did not change the responses to electrical stimulation. The results suggest that the electrically induced adrenergic activation of urethral muscle of both rabbit and man was mediated mainly via alpha-adrenoceptors and that this muscle is innervated not only by sympathetic, adrenergic nerves but also by a type of nerve able to release a non-cholinergic, contraction-mediating transmitter.

Adrenergic Fibers↗

PubMed1985

Contractant and relaxant properties of the female rabbit urethral submucosa.

Isolated submucosal (lamina propria) preparations from the female rabbit urethra exhibited both contractant and relaxant properties. The nerve-mediated contraction to electrical field stimulation was adrenergic in nature, and both this response and the contraction induced by exogenous application of noradrenaline were blocked to a greater extent by alpha 2 than by alpha 1-adrenoceptor blocking agents. Vasoactive intestinal polypeptide was found to be a potent inhibitor of the noradrenaline-mediated contraction. Neuropeptide Y induced contraction of the preparation, but also inhibited the nerve-mediated contractant response. In noradrenaline-contracted preparations, electrical field stimulation induced a non-adrenergic, non-cholinergic relaxation. The maximum relaxant response was significantly greater when the preparations were contracted by clonidine than by noradrenaline. Abundant smooth muscle cells with no obvious connection to vessel walls were found in the submucosa, but to what extent the contractant and relaxant responses can be ascribed to vascular or non-vascular smooth muscle is not settled. The results indicate a non-uniform distribution of the peripheral nervous control within the wall of the female rabbit urethra. The demonstrated contractant and relaxant properties of the submucosal tissue might be of importance for urethral function.

Adrenergic alpha-Antagonists↗

PubMed1984

Differential effects of nifedipine, verapamil, and diltiazem on noradrenaline-induced contractions, adrenergic transmitter release, and alpha-adrenoceptor binding in the female rabbit urethra.

In order to study differences in action between "Ca2+-entry blockers" on smooth muscle and peripheral nerves, the effects of nifedipine, verapamil, and diltiazem on noradrenaline (NA)-induced contractions and electrically evoked release of 3H-NA were investigated in the female rabbit urethra. In addition, possible influences of Ca2+-entry blockers on alpha-adrenoceptors were studied with radioligand binding technique. Exposure to Ca2+-free medium completely abolished the contractile response to 1 microM NA in the rabbit urethra, indicating that the contraction was entirely dependent on influx of extracellular Ca2+. The Ca2+-entry blockers inhibited the NA-induced contractions in the following order of potency: nifedipine greater than verapamil approximately equal to diltiazem. In contrast to nifedipine and diltiazem, which produced a maximum inhibition of between 50 and 60%, verapamil was able to abolish the contractile responses to NA. The electrically evoked efflux of 3H-NA was decreased by diltiazem and increased by verapamil, whereas nifedipine failed to alter the 3H-NA efflux. Only verapamil was effective in inhibiting specific 3H-DHE binding to a crude membrane preparation of the rabbit bladder base and urethra, and the inhibition appeared to be of the competitive type. It is suggested that the effects of verapamil on electrically evoked efflux of 3H-NA and on NA-induced contractions can be partly explained by blockade of pre- and post-junctional alpha-adrenoceptors. The failure of nifedipine and diltiazem to abolish the NA-induced contraction might indicate the existence of different Ca2+-entry pathways in urethral smooth muscle.

Animals↗

PubMed1984

Collagen content in the rat urinary bladder subjected to infravesical outflow obstruction.

Collagen content was determined in the detrusor muscle from control rats and rats subjected to infravesical outflow obstruction for periods of 3 days to 4 months. During the 1st 6 weeks of obstruction the detrusor weight increased 12-fold. The total amount of detrusor collagen increased by a factor of 4, while the concentration of collagen decreased to 1/3 of the initial concentration. A longer period of obstruction, 4 months, did not further affect detrusor weight or collagen content or concentration. Ultrastructurally, both normal and hypertrophic detrusor showed a great number of collagen fibrils (probably synthetized by fibrocytes) between the smooth muscle bundles. Collagen fibrils (probably synthesized by the smooth muscle cells) could also, although less frequently, be found within the bundles. The decreased collagen concentration in the hypertrophic detrusor could largely be explained by a coalescence of the smooth muscle bundles resulting in a relative increase of this tissue component.

Animals↗

PubMed1984

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.

Animals↗

PubMed1984

Supersensitivity to carbachol in the parasympathetically decentralized feline urinary bladder.

We investigated the concentration-response relations for carbachol, the morphological characteristics and the mechanical properties of feline detrusor strips from 1) normal cats, cats subjected to 2) parasympathetic sacral decentralization, 3) urinary diversion followed by parasympathetic sacral decentralization and 4) urinary diversion only. Hypertrophy of the detrusor and supersensitivity to carbachol (a decrease of EC50) were found only after parasympathetic decentralization. No hypertrophy developed and no change in the EC50-value for carbachol was found if urinary diversion preceded the parasympathetic decentralization. A decreased ability of force production per unit cross sectional smooth muscle area was found in the decentralized bladders compared to the controls. However, the total ability of force production and hence also pressure production of the decentralized bladders would be expected to be enhanced due to a 4 to 5-fold increase of bladder weight (mainly muscle mass). No differences in the active length-tension relations were found in the 4 groups. It is suggested that parasympathetic decentralization per se does not give rise to detrusor hypertrophy or increased sensitivity to carbachol. Provided that the situation in man is comparable to that in the cat, it might be that the supersensitivity test a.m. Lapides-Glahn reflects the presence of detrusor hypertrophy rather than the presence of a neurogenic lesion.

Animals↗

PubMed1984

Adrenoceptors and cholinoceptors controlling noradrenaline release from adrenergic nerves in the urethra of rabbit and man.

The possible influence of adreno- and cholinoceptors on noradrenaline release from adrenergic nerve endings in urethral smooth muscle of rabbit and man was investigated in preparations preincubated with 3H-noradrenaline. The preparations were continuously perfused in a temperature controlled ( 37C ) chamber and the amount of electrically induced efflux of 3H calculated as a fraction of the total amount of 3H in the preparation at the time of stimulation. In preparations from both rabbit and man, the fractional release of 3H induced by electrical field stimulation was reproducible, and significantly increased in the presence of the alpha 2-receptor antagonist rauwolscine and the muscarinic cholinoceptor antagonists scopolamine and atropine. There was a significant decrease of 3H-release in the presence of the alpha 2-receptor agonist clonidine and the cholinoceptor agonist carbachol. No evidence for the presence of prejunctionally located alpha 1 or nicotinic receptors was found. The results suggest the possibilities of 1) a negative feed-back regulation of the release of noradrenaline from adrenergic nerve endings in the urethra, mediated via prejunctionally located alpha 2-adrenoceptors, 2) an interaction at the nerve terminal level between adrenergic and cholinergic nerves mediated via muscarinic cholinoceptors on the adrenergic nerve terminals.

Adrenergic Fibers↗

PubMed1984

Pre- and postjunctional adreno- and muscarinic receptor functions in the isolated human corpus spongiosum urethrae.

In isolated tissue from the human corpus spongiosum urethrae (CS) the effects of adrenoreceptor and muscarinic receptor active drugs on release of 3H-noradrenaline (NA) from noradrenergic nerves and on isometric tension were investigated. The electrically induced release of 3H was reduced by clonidine (alpha 2-adrenoreceptor agonist), increased by rauwolscine (alpha 2-adrenoreceptor antagonist), and little affected by phenylephrine (alpha 1-adrenoreceptor agonist) and prazosin (alpha 1-adrenoreceptor antagonist). Isoprenaline (beta 1- and beta 2-adrenoreceptor agonist) and procaterol (beta 2-adrenoreceptor agonist) increased the release, propranolol (beta 1- and beta 2-adrenoreceptor antagonist) reduced it, and prenalterol (beta 1-adrenoreceptor agonist) and atenolol (beta 1-adrenoreceptor antagonist) had no effect. Carbachol (muscarinic receptor agonist) decreased and scopolamine (muscarinic receptor antagonist) increased stimulation-induced efflux of 3H. NA, phenylephrine and clonidine contracted isolated CS preparations, clonidine being less potent and having less intrinsic activity than phenylephrine. Prazosin was more effective than rauwolscine for inhibition of NA-induced contractions, and prazosin, but not rauwolscine, abolished electrically induced contractions. Isoprenaline and procaterol, but not prenalterol, relaxed NA-contracted preparations. These relaxations could be blocked by propranolol but not by atenolol. Acetylcholine and carbachol relaxed NA-contracted preparations but had no contractant effect on any of the preparations tested. The results suggest that prejunctionally in the human CS, the alpha-adrenoreceptors are of alpha 2-type and the beta-adrenoreceptors of beta 2-type. Postjunctionally, the main alpha-adrenoreceptor function seems to be of alpha 1-type and the beta-adrenoreceptor function of beta 2-type. Stimulation of muscarinic receptors may inhibit the effects of NA both by decreasing its release from noradrenergic nerves and by counteracting its postjunctional effects.

Adrenergic alpha-Agonists↗