Biomedical subjects

B Uvelius

Publications and source records attributed to B Uvelius.

At least 55 records · Page 3Linked to original sources

PubMed1993

Effect and content of arginine vasopressin in normal and obstructed rat urinary bladder: an in vivo and in vitro investigation.

The present investigation was performed to evaluate the possible role of arginine vasopressin (AVP) in detrusor instability in the obstructed rat urinary bladder. The effect of AVP on normal and obstructed rat detrusor smooth muscle was tested in vivo and in vitro. Arginine vasopressin given as a closed intraarterial injection to the bladder transiently decreased micturition volume and increased micturition frequency during cystometry in control rats. In rats with infravesical outlet obstruction the effect of AVP on cystometrical parameters was negligible. In accordance with this finding, the efficacy of AVP in contracting detrusor muscle in vitro was much lower for obstructed bladders than for controls. The EC50 values were, however, similar. Arginine vasopressin added to the bath had no effect on nerve-mediated contractile responses. Obstruction led to a transient decrease in immunoreactive AVP concentration, but the total amount of AVP per bladder increased significantly after 6 weeks of obstruction as a consequence of the 14-fold increase in bladder weight. The decreased excitatory effect of AVP in obstructed bladder makes a role for this peptide in the development of detrusor instability less likely.

Animals↗

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

Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes.

Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7-8 wk duration). Bladder wet wt was almost 4-fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to PO2 100 mmHg for both control and diabetic muscle strips. At zero PO2 force was reduced by approximately 10-20%, in both groups. High-K+ solution induced 'tonic' contractions that were slightly more inhibited by lowering PO2. At intermediate PO2 (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero PO2 no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a PO2 of 290 mmHg and related to the volume of smooth muscle. At zero PO2, lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero PO2. No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue samples was about 2-fold higher in the diabetic bladder muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of unilateral pelvic ganglionectomy on urinary bladder function in the male rat.

Micturition interval and micturition volume were measured in water loaded male rats before and up to 6 weeks after unilateral pelvic ganglionectomy. There was no effect on micturition interval until 7 days after the ganglionectomy. Micturition interval then remained increased. Maximal micturition volume was higher than in the control group from 4 to 14 days after surgery. Cystometrograms were recorded 12 days or 6 weeks after surgery. At 12 days the micturition pressure was lower in the unilaterally ganglionectomized than in the controls. After 6 weeks there was no significant difference in micturition pressure. A reduction of micturition pressure by about 50% was observed after i.v. injection of atropine, but no residual urine developed. Electron microscope investigation showed a considerable decrease in number of nerve terminals on the ganglionectomized side 3 days after surgery. Most of them were devoid of synaptic vesicles. On the contralateral side the majority of nerve terminals appeared normal, but many had a decreased number of vesicles. After 14 days the number of terminals was still lower than normal on the ganglionectomized side. They generally contained only a small number of vesicles. Also, on the contralateral side some nerve endings with the reduced complement of vesicles were found. We suggest that the effects of unilateral ganglionectomy on micturition volume and interval can be explained by a decreased sensory input from the bladder and that the effect on micturition pressure is due to a transient decrease in number and function of motor nerve terminals in the detrusor muscle.

Animals↗

PubMed1992

Hypertrophy and reversal of hypertrophy in rat pelvic ganglion neurons.

An experimental procedure which chronically reduces the lumen of the urethra in adult female rats produced distension of the bladder and conspicuous thickening of its wall, resulting within 6-8 weeks in a ten-fold increase in muscle weight (muscle hypertrophy). During this process, the neurons in the pelvic ganglion that innervate the bladder undergo a large increase in size (neuronal hypertrophy). The average neuronal volume increased by 83%; small neurons became less numerous and large neurons became more numerous than in controls, but there was no increase in the maximum neuronal size. Six weeks after re-operation and removal of the urethral obstruction, the weight of the bladder was reduced (although not quite to the control levels), while the average neuronal size reversed to values very close to controls. In separate experiments, the pelvic ganglion of one side was removed. The nerve fibres in the hemidenervated bladder sprouted, grew and spread to innervate the whole bladder. The neurons in the surviving pelvic ganglion hypertrophied, the average cell volume increasing by 50% in seven weeks. The experiments showed that: (i) the pelvic neurons of adult rats are capable of very extensive growth when the tissue they innervate (bladder muscle) undergoes hypertrophy; (ii) the neuronal hypertrophy is reversible. This was taken to imply that there are factors within the bladder, including trophic substances, that regulate nerve cell volume not only by inducing growth but also by inducing the opposite effect, a cell size reduction; (iii) unilateral ganglionectomy, which did not induce muscle hypertrophy but doubled the amount of muscle innervated by the contralateral ganglion, was followed by marked neuronal hypertrophy.

Animals↗

PubMed1992

Contractile effect and tissue content of arginine vasopressin in the urinary bladder of Brattleboro rats with hereditary diabetes insipidus.

1. Urinary bladders from male rats of the Brattleboro strain with hereditary diabetes insipidus (DI) were analyzed for presence of immunoreactive arginine vasopressin (ir-AVP). Healthy rats were used as controls. 2. Bladders from the DI rats were heavier than controls. Concentration of ir-AVP was lower in DI bladders, but total amount of ir-AVP was similar to that in controls. 3. EC50 values for the AVP concentration-response relations were similar for control and DI bladder strips. Maximum response to AVP relative to response to K+ high solution was lower in the DI group. 4. An AVP receptor antagonist that significantly blocked response to exogenous AVP had no effect on response to field stimulation. 5. We suggest that AVP is synthetized locally and that AVP is not the non-adrenergic non-cholinergic transmitter responsible for the atropine resistant contraction in rat bladder.

Animals↗

PubMed1992

Urinary bladder function in rats with hereditary diabetes insipidus; a cystometrical and in vitro evaluation.

Bladder function was investigated in female rats with hereditary diabetes insipidus (DI) and in healthy controls, in vivo by means of recordings of micturition pattern and cystometry, and in vitro in organ bath experiments. Rats with DI exhibited bladder hypertrophy, the weight of the bladder in these rats being two times that of controls. Recordings of micturition pattern showed that DI-rats had an increased 24 hour diuresis and micturition volume, and decreased micturition interval in comparison with controls. Cystometry recordings revealed increased bladder capacity and micturition volume in DI-rats. However, in these rats basal bladder pressure and threshold pressure were lower than in controls. No significant changes in micturition pressure or bladder compliance were observed, and none of the rats had residual urine. In organ bath studies, a lower maximal response to electrical field stimulation was obtained in bladder strips from DI-rats, than in the control strips, when expressed relative to the response elicited by K(+)-solution. When activated by field stimulation, the DI-bladder strips and the control strips had similar sensitivity to muscarinic receptor blockade with scopolamine at all stimulation frequencies. The sensitivity to carbachol was similar in the two groups. The results suggest that the increased functional demands of DI on the detrusor do not result in major changes pre- or postjunctionally. Further, several of the previously reported urinary bladder changes observed in rats with diabetes mellitus (DM) are similar to those now reported in rats with DI, emphasizing the importance of an increased diuresis per se for the development of alterations in bladder function. However, in contrast to the findings in DM rats, the sensitivity to electrical stimulation of nerves during blockade of muscarinic receptors was similar in DI-rats and their controls. This supports our previous suggestion that the increased resistance to muscarinic receptor blockade of the bladder in DM-rats at low stimulation frequencies is induced by the disease (diabetes mellitus) as such and not by the increased diuresis.

Animals↗

PubMed1992

Effects of age and streptozotocin-induced diabetes on contents and effects of substance P and vasoactive intestinal polypeptide in the lower urinary tract of the rat.

The urinary bladder and urethral content of substance P and vasoactive intestinal polypeptide and the in vitro effects of the peptides on the bladder were studied at 6 weeks and 6 months of streptozotocin-induced diabetes in the rat. The results were compared with those obtained in age-matched control animals. Both short-term and long-term streptozotocin treatment induced a clearcut increase in bladder weight. Bladder substance P content was increased in both groups of diabetic animals but substance P concentration was similar in control and diabetic animals. Vasoactive intestinal polypeptide content was slightly higher in diabetic animals than in controls but vasoactive intestinal polypeptide concentration was significantly lower in the bladders from both short-term and long-term diabetic animals. The bladder contractile response to substance P was similar in all groups of animals and vasoactive intestinal polypeptide was found to be devoid of contractile or relaxatory effects in the rat bladder. No change in urethral weight was seen with diabetes. There were no clear-cut changes in the urethral contents or concentrations of substance P and vasoactive intestinal polypeptide. The study also enabled comparisons between younger (3 months) and older (9 months) rats. This comparison showed a decrease in the concentrations and contents of substance P and vasoactive intestinal polypeptide between young and older rats. The changes were seen in both the bladder and the urethra and were similar in diabetic and normal animals.

Aging↗

PubMed1991

Lactate dehydrogenase activity and isoform distribution in normal and hypertrophic smooth muscle tissue from the rat.

The lactate dehydrogenase (LDH) activity and isoform distribution of LDH were investigated in tissue samples from the rat portal vein, aorta and urinary bladder. In addition, samples were obtained from hypertrophic urinary bladder. The total LDH activity per unit smooth muscle volume was higher in the urinary bladder compared to that in portal vein and aorta. Five LDH isoforms, reflecting different combinations of the two polypeptide chains denoted H and M, could be separated by agarose gel electrophoresis. The aorta contained more of the H form compared to the portal vein and urinary bladder. This difference suggests that the aorta, which is a slow smooth muscle, is more adapted for aerobic metabolism than the faster muscles of portal vein and urinary bladder. In the hypertrophic urinary bladder a shift in LDH isoform pattern towards less of the H form was found, which correlates with a better maintenance of contraction in anoxia in this type of hypertrophic smooth muscle.

Animals↗

PubMed1991

Mechanics and Ca(2+)-sensitivity of human detrusor muscle bundles studied in vitro.

Mechanical properties of isolated smooth muscle strips from human urinary bladder were investigated in vitro. Bladder tissue was obtained from tumour-free wall regions of bladders from male patients undergoing cystectomy for bladder carcinoma. In intact muscle strips, activated with high-K+ solution, half-maximal force occurred at about 0.9 mM extracellular [Ca2+]. The length-active force relation was determined and the muscle strips were fixed for light and electron microscopy at optimal length for active force (1o). The maximal active force per unit smooth muscle cross-sectional area was 208 +/- 49 mN/mm2, n = 6. Chemically skinned preparations were obtained by treatment with triton X-100. These preparations had a steep [Ca2+]-force relation in the micromolar range which was influenced by calmodulin. The skinned preparations could be maximally activated by irreversible thiophosphorylation of the regulatory light chains. The force-velocity relation was determined in the maximally activated skinned muscle at 22 degrees C at 0.51o. When the muscle was shortened by 10%, force was reduced by 35% whereas the maximal shortening velocity was little affected.

Aged↗

PubMed1991

Contractile and cytoskeletal proteins in smooth muscle during hypertrophy and its reversal.

Hypertrophy of rat urinary bladder smooth muscle was induced by partial urethral obstruction. Bladder weight increased from 70 to 240 mg after 10 days and to 700 mg after 7 wk. Removal of the obstruction after 10 days caused a regression of bladder weight to 130 mg. The relative volume of smooth muscle in the bladder wall increased during hypertrophy. The concentration of myosin in the smooth muscle cells decreased in 10-day hypertrophied bladders, whereas the concentration of actin was unchanged. The actin-myosin ratio was 2.3 in controls, 3.3 in 10-day obstructed bladders, and 2.9 in 7-wk obstructed bladders. After removal of obstruction, the ratio was normalized. Two isoforms of myosin heavy chains were identified (SM1 and SM2). The relative amount of SM2 decreased during hypertrophy. The relative proportion of actin isoforms (alpha, beta, and gamma) was altered toward more gamma and less alpha. These changes were reversible upon removal of the obstruction. Desmin was the dominating intermediate filament protein. The concentration of desmin and filamin increased in the hypertrophic bladders. The increased desmin-actin and filamin-actin ratios in obstructed bladders were normalized after removal of the obstruction. The results suggest that the turnover of contractile and cytoskeletal proteins is fast and can be regulated in response to changes in the functional demands in smooth muscle.

Actins↗

PubMed1991

Collagen content in the rat urinary bladder following removal of an experimental infravesical outlet obstruction.

A partial urethral obstruction was induced in female rats. After 6 weeks, detrusor weight had increased eightfold and collagen concentration had decreased to about 40% compared to controls. Due to the weight gain, the total amount of detrusor collagen had increased more than threefold. Removal of the obstruction led to a rapid decrease in detrusor weight to 70, 34 and 30%, 2, 4 and 6 weeks postobstruction, although control levels were not reached. Collagen content decreased more slowly than detrusor weight, and for the same groups was 97, 69 and 67% of the value in the obstructed detrusor. This led to a rapid increase in detrusor collagen concentration which already 4 weeks after removal of the obstruction had increased to a level that did not significantly differ from the control value. The discrepancy between decrease in detrusor weight and in collagen content after removal of the obstruction suggests that a large proportion of the collagen synthesized during the period of outlet obstruction remained. Changes in the ratio between muscle and nonmuscle tissue were limited between control, obstructed and nonobstructed bladders. This suggests that the collagen concentration following obstruction and removal of obstruction is to a large extent due to changes in collagen concentration in the interstitial connective tissue rich in collagen.

Animals↗

PubMed1991

Cytoskeletal and contractile proteins in detrusor smooth muscle from bladders with outlet obstruction--a comparative study in rat and man.

Detrusor biopsies were obtained from patients with urinary outlet obstruction due to prostatic enlargement and from age-matched control patients. The relative amounts of actin and myosin and their isoforms, as well as desmin and filamin were determined and compared with corresponding results from bladders from control rats and rats with 10 days of experimental outlet obstruction of the urinary bladder. In the human control detrusor the actin/myosin ratio was similar to that in the control rat. The isoform distribution of the myosin heavy chains differed between man and rat. In the biopsies from the patients with outlet obstruction and in the obstructed rat bladders the actin/myosin ratio was increased. A change in the myosin heavy chain distribution in the obstructed bladders was observed for both species. The filamin/actin ratio increased significantly in the obstructed rat bladders and tended to increase in the obstructed human bladders. Desmin was the dominating intermediate filament protein. The desmin/actin ratio increased in obstructed bladders in man and in rat.

Actins↗

PubMed1990

Content and contractile effect of arginine vasopressin in rat urinary bladder.

The contractile response of normal male rat urinary bladders to exogenous arginine vasopressin (AVP) and the AVP content of normal and denervated bladders were investigated. In isolated detrusor strips, the maximal response to AVP was about 12% of the contraction elicited by KCl (124 mM), and the EC50 value was 1.03 +/- 0.13 x 10(-8) M. The response to transmural nerve stimulation was not affected by the presence of AVP. Addition of an AVP receptor antagonist strongly reduced the response to exogenous AVP, but did not affect contractions in response to nerve stimulation. In normal bladders, the concentration of immunoreactive (ir) AVP was 29 +/- 6.0 x 10(-15) mol/g. Three days after denervation the bladders had increased 2.4-fold in weight. At this time, the concentration of irAVP was not different from the control value, but the total content had increased significantly. Characterization of bladder irAVP by reverse-phase HPLC revealed that 66.5% of the total immunoreactivity eluted in the position of synthetic AVP. The results suggest a non-neuronal localization of bladder irAVP.

Animals↗

PubMed1990

Urinary bladder of rat: fine structure of normal and hypertrophic musculature.

The fine structure of the muscle of the urinary bladder in female rats is similar to that of other visceral muscles, although it is arranged in bundles of variable length, cross-section and orientation, forming a meshwork. When distended, the musculature is 100-120 microns thick, with some variation and occasional discontinuity. Extended areas of cell-to-cell apposition with uniform intercellular space occur between muscle cells, whereas attachment plaques for mechanical coupling are less common than in other visceral muscles. There are no gap junctions between muscle cells. Many bundles of microfilaments and small elastic fibres run between the muscle cells. After chronic partial obstruction of the urethra, the bladder enlarges and is about 15 times heavier, but has the same shape as in controls; the growth is mainly accounted for by muscle hypertrophy. The outer surface of the hypertrophic bladder is increased 6-fold over the controls; the muscle is increased 3-fold in thickness, and is more compact. Mitoses are not found, but there is a massive increase in muscle cell size. There is a modest decrease in percentage volume of mitochondria, an increase in sarcoplasmic reticulum, and no appreciable change in the pattern of myofilaments. Gap junctions between hypertrophic muscle cells are virtually absent. Intramuscular nerve fibres and vesicle-containing varicosities appear as common in the hypertrophic muscle as in controls. There is no infiltration of the muscle by connective tissue and no significant occurrence of muscle cell death.

Animals↗

PubMed1990

Nerve-mediated functions in the circular and longitudinal muscle layers of the proximal female rabbit urethra.

In the present study, nerve mediated functions in the circular and longitudinal muscle layers of the female rabbit urethra were characterized. Based on light microscopic findings, the interest was focused on the proximal third of the organ. A microsurgical dissection technique was developed, allowing separation of the two muscle layers. The following studies were carried out: functional in vitro investigations including exogenous application of drugs and electrical field stimulation, investigations of the release of 3H-noradrenaline (NA), and autoradiography for visualization of muscarinic receptors. The results can be summarized as follows: the adrenergic nervous influence, which was mediated mainly via alpha 1-adrenoceptors, dominated the contractile response of the circular layer and contributed significantly to the contraction of the longitudinal layer. A previously described fast, non-adrenergic, non-cholinergic response was found in the circular muscle layer. This response should probably be ascribed to striated muscle with a different innervation and/or structure than skeletal muscle in general. Muscarinic cholinoceptors were abundant in the outer parts of the urethral wall and decreased in density in luminal direction. A significant cholinergic contractile component was demonstrated in the longitudinal muscle. A non-adrenergic, non-cholinergic nerve-mediated relaxant response was found in both layers, although more pronounced in the circular one. Vasoactive intestinal polypeptide completely relaxed both circular and longitudinal preparations contracted by noradrenaline. A possible basis for an interaction between adrenergic and cholinergic nerve endings was demonstrated in the circular muscle layer. Stimulation of muscarinic receptors on the adrenergic nerve endings markedly reduced the release of 3H-NA. The present results support the findings in previous studies on circularly and longitudinally oriented full-thickness preparations of the female urethra and further underline the differences in structure, innervation and receptor functions between the different muscle layers of the urethral wall.

Adrenergic Fibers↗

PubMed1990

On the reversibility of functional bladder changes induced by infravesical outflow obstruction in the rat.

Rats were subjected to infravesical outflow obstruction for six weeks. The bladder function was followed by cytometrical and in vitro investigations and by recordings of micturition pattern before and after removal of the obstruction. Cytometrical investigations showed that outflow obstruction for six weeks induced a bladder instability. Further, in the presence of obstruction the micturition pressure was large as was the bladder capacity and the rats had residual urine. After removal of the obstruction the bladder function rapidly normalized. The bladder instability disappeared within one week, bladder capacity decreased as did the micturition pressure. Moreover, only a minor amount of residual urine was present post-obstruction. In vitro investigation showed that the response to carbachol and to electrical stimulation was similar in normal and obstructed bladders. However, after removal of the obstruction a supersensitivity to carbachol as well as to electrical stimulation had developed. Obstructed bladders showed a markedly decreased response to substance P. The sensitivity to substance P was rapidly enhanced post-obstruction and after four days the response was restored to the control level. The present study shows that the bladder function in rats with infravesical outflow obstruction rapidly normalized after removal of the obstruction. The disappearance of the bladder instability despite the developed supersensitivity to muscarinic receptor stimulation supports the opinion that the bladder instability is not of muscarinic origin.

Animals↗

PubMed1990

Functional responses of different muscle types of the female rat urethra in vitro.

The influence of muscle type on functional responses of the female rat urethra was investigated using morphological and functional in-vitro techniques. The urethral submucosa was found to contain longitudinally or obliquely oriented smooth muscle cells. The muscularis layer is composed of circularly oriented muscle cells. Near the bladder orifice smooth muscle fibres dominate, but in the mid-urethra the vast majority is circularly oriented striated muscle cells. Circular preparations responded to electrical field stimulation in vitro with a rapid contraction. Stimulation with single impulses resulted in a twitch response; frequencies exceeding 5-10 Hz induced a summation and tetanus. The response was unaffected by phenoxybenzamine, propranolol and scopolamine and had a low sensitivity to calcium-free solution but was sensitive to suxamethonium and tetrodotoxin. Using longer impulse trains stimulation evoked also a slow contraction, sensitive to calcium-free solution. In longitudinal preparations stimulation induced a relaxation followed by a contraction, responses much smaller than those seen in the circular preparations. Both preparations relaxed on addition of calcitonin gene-related peptide or capsaicin. The relaxation to calcitonin gene-related peptide was larger than that to capsaicin in longitudinal preparations but equally large in the circular ones. Substance P and 5-hydroxytryptamine contracted both preparations. The longitudinal urethra showed a larger contraction to 5-hydroxytryptamine than to substance P, whereas both substances induced similar responses in the circular preparations. The study shows a similar muscle arrangement in the female rat urethra as described in humans and further points to a functional differentiation between the different types of muscle.

Animals↗