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Biomedical subjects

B Uvelius

Publications and source records attributed to B Uvelius.

At least 91 records · Page 5Linked to original sources

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↗

Effects of Ca2+ on force-velocity characteristics of normal and hypertrophic smooth muscle of the rat portal vein.

Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days of hypertension the portal veins were taken out and mounted for isometric and quick-release experiments. Portal veins from sham-operated normal rats served as controls. The ligated veins had an increased cross-sectional area, indicating smooth-muscle hypertrophy. Although the absolute magnitude of active force of these veins was increased, the active force per cross-sectional area was decreased, indicating an alteration in the properties of the contractile system. No difference in the Ca2+ concentration-response relations to K+-activated intact control and hypertrophic veins was found. In chemically skinned preparations, devoid of functional plasma membranes, the hypertrophic veins had similar Ca2+ sensitivity (in the presence of I microM calmodulin) but a lower force per cross-sectional area. Force-velocity relations were determined in K+-activated intact preparations. In control veins a reduction in extracellular Ca2+ was associated with a significant reduction in both isometric force and maximal shortening velocity (Vmax). In hypertrophic veins the decreased isometric force at maximal activation was associated with a low Vmax. A comparison between hypertrophic and submaximally stimulated control vessels showed corresponding Vmax and isometric force values. We conclude that the low isometric force of hypertrophic veins is associated with a lower rate of cross-bridge turnover. This could be an effect of alterations in the activation mechanisms or in the intrinsic properties of the contractile system itself.

Animals↗

Renal polyamine metabolism in rats with renovascular hypertension.

A standardized stenosis was induced by applying a silver clip around the left renal artery in male rats. This resulted in arterial hypertension within 10 days (as determined by increase in heart weight). Ornithine decarboxylase (ODC) activity was determined in the right (untouched) kidney, the left kidney, and the adrenal glands 1 day, 10 days, and 3 months after the operation. There was no difference in ODC activity in the right kidney of the operated animals when compared with matched controls. In the left kidney (with artery stenosis), ODC activity decreased to 40% after 1 day. A partial recovery was seen after 10 days (ODC activity 70% of normal), and after 3 months ODC activity had normalized. Removal of the clip 1 day prior to killing induced in the 3-month group a more than two-fold increase in ODC activity in the previously clipped kidney; ODC activity in the contralateral kidney was not affected. Only minor changes in ODC activity occurred in the adrenal glands following the operation. Contents of putrescine and spermidine were increased in the left (stenotic) kidney, and after clip removal, also in the right (untouched) kidney. Our observations thus indicate that alterations in renal blood flow are rapidly followed by changes in ODC activity. Contents of putrescine, spermidine and spermine seemed to a great extent to be independent of the ODC activity.

Adrenal Glands↗

Effects of variations in extracellular osmolality on spontaneous contractile activity and response to nerve stimulation in rat detrusor muscle in vitro.

The effects of hyperosmolar (390, 590 mosm/kg) and hypoosmolar (260 mosm/kg) solutions on myogenic spontaneous contractile activity and response to nerve stimulation were studied on strips of rat detrusor muscle in vitro. In isotonic (290 mosm/kg) solution the mean spontaneous contractile activity was 2.1 +/- 0.6% and the amplitude of the largest spontaneous contractions was 9.8 +/- 3.0% of maximal response to nerve stimulation. In 390 mosm/kg the frequency of spontaneous contractions decreased, but due to a fourfold increase of contraction amplitude a threefold increase of mean contractile activity was recorded. In 260 mosm/kg a similar contraction pattern as in 290 mosm/kg was seen. The spontaneous contractions were resistant to tetrodotoxin (10(-5) g/ml) in all osmolalities. In 590 mosm/kg the spontaneous activity had ceased, and a continuous contracture (resistant to tetrodotoxin) was observed with an amplitude of 41 +/- 1% of the maximal response to nerve stimulation at 290 mosm/kg. Similar maximal responses to nerve stimulation were obtained in 260, 290, and 390 mosm/kg. The frequency-response relation in 390 mosm/kg had a leftward shift at low frequencies. In 590 mosm/kg no response to nerve stimulation or acetylcholine was noted, but the preparations contracted vigorously following depolarization with high-K+ solution.

Animals↗

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↗

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↗

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↗

Structural and mechanical adaptations in rat aorta in response to sustained changes in arterial pressure.

Structural and mechanical adaptations in response to sustained changes in arterial pressure were studied on abdominal aorta of the male rat. Two models were used: 1. Aortic ligature (L), immediately below the renal arteries producing hypotension distal to the knot (duration before sacrifice 6 weeks or 3 months). 2. One-clip renal hypertensive rats (H) (duration 6 weeks). Normotensive sham-operated rats (C) served as controls. At sacrifice mean tail artery pressure was L: 58 +/- 1, C: 110 +/- 3, and H: 163 +/- 5 mmHg (SE, N=6). Segments of abdominal aorta were mounted in vitro for determination of their length-tension relations (activation: High-K+ solution with 2.5 mM Ca2+). At end of experiments the vessels were supramaximally stimulated at optimal circumference (1o) for active force (activation: High-K+ solution with 10 mM Ca2+, and 10(-5) M noradrenaline), and then fixated for light and electron microscopy. Passive and active length-tension relations were shifted towards lower and higher circumference values for hypo- and hypertensive vessels, respectively. The 1o values were L: 3.60 +/- 0.13, C: 4.44 +/- 0.19, and H: 4.91 +/- 0.29 mm. The media thickness at 1o was reduced in L: 56.0 +/- 3.3, and increased in H: 81.3 +/- 2.4 compared to C: 73.4 +/- 1.8 micron. Maximal active wall stress was L: 46.6 +/- 9.8, C: 74.2 +/- 7.0, and H: 83.8 +/- 7.7 mN/mm2. Intracellular volume (ICV) in the media was L: 30 +/- 2, C: 45 +/- 3, and H: 44 +/- 1% (n=4 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Membrane potential in smooth muscle cells from hypertrophic rat portal vein.

Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days the vein was removed and mounted in vitro. In contrast to control (C) veins, hypertensive (H) vessels were almost devoid of spontaneous contractions. Microelectrode recordings showed that the smooth muscle cells of H vessels were hyperpolarized. If [K+]o was increased, or if Ba2+ was added spontaneous activity could be initiated in H vessels. A relation in H cells between hyperpolarization and increased aerobic glycolysis (suggesting an increased electrogenic Na+-K+-pumping) is proposed.

Animals↗

The effects of Ca2+ and Sr2+ at different modes of activation in the smooth muscle of the rat portal vein.

The dependence of Ca2+ for different modes of activation has been investigated in the rat portal vein in vitro by evaluating the effects of substituting Sr2+ for Ca2+ in the extracellular fluid. For the spontaneous contractile activity as well as for contractures induced by depolarizing (high-K+) solution Sr2+ can to a large extent replace Ca2+. Sr2+ is however a poor Ca2+-substitute for the contractile response induced by alpha-stimulation (noradrenaline). The inhibition of spontaneous contractions by beta-stimulation (isoprenaline) is markedly less pronounced in Sr2+ solutions. Available data in the literature suggest that agonist interaction with alpha-receptors, in contrast to beta-receptors, is Ca2+ independent. Our results thus suggest that there exists a Ca2+ specific step between the alpha-receptor agonist occupancy and membrane excitation.

Adrenergic alpha-Agonists↗

Changes in length and volume of smooth muscle cells of the hypertrophied rat urinary bladder.

Rat urinary bladders were denervated by bilateral excision of the pelvic ganglion. After 10 days the hypertrophied bladders were removed, filled with 0.75 ml Krebs solution, fixated and embedded for electron microscopy. Normal bladders filled with the same volume were used as controls. Tangential and transverse sections of longitudinal muscle bundles were cut both for phase contrast and electron microscopy. The profiles of cross-sectioned cells from control bladders had regular, often almost circular contours, and were rather uniform in size. The cell contours from the denervated bladders were irregular with wrinkled surfaces and the cells varied considerably in size. In tangential sections the cells from denervated bladders had corrugated surfaces in contrast to the control cells. Mean length and volume of the muscle cells were determined morphometrically. Whereas cell volume was larger in denervated (3 800 microns 3) than in control bladders (2 200 mu 3), cell length was less (226 versus 335 microns). The finding of shorter cells in denervated bladders favour the opinion, brought forward previously (Ekström & Uvelius 1981), that the rightward shift of the active length-tension curve in denervated bladders is due to an increase in the number of muscle cells that are coupled in series around the bladder circumference.

Animals↗

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.

Animals↗

Force-velocity characteristics and active tension in relation to content and orientation of smooth muscle cells in aortas from normotensive and spontaneous hypertensive rats.

Segments of abdominal aorta from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats (20-25 weeks) were compared with respect to force production and dynamic mechanical properties. The preparations were mounted in vitro for determination of optimal length (lo) for active force, and then maximally stimulated (high-K+ solution, 10 mm Ca2+, 10(-5) m noradrenaline), and fixed for electron microscopy. Muscle cellular volume per mm vessel wall was significantly (p less than 0.01) higher in SHR (0.14 +/- 0.009 mm3, n = 7) compared to WKY (0.11 +/- 0.004 mm3, n = 7). Unchanged cell length and unaltered cross-sectional area (17 micrometers2) of nucleus containing cell profiles in SHR suggest an increased number of cells in the media. No difference was found in maximum force per unit cell area between SHR (271 +/- 31, n = 7) and WKY (305 +/- 49 mN/mm2, n = 7). Cell orientation was almost circular in both groups, showing that force was measured in parallel to the cell long axis. Aortic segments were mounted in an apparatus for quick-release experiments. They were maximally stimulated and force steps were imposed at peak of contractions. The series elastic component, characterized by the initial elastic recoils at 0.75 lo, has similar stiffness values in SHR and WKY. Velocities were measured 100 msec after release. The results were fitted to Hill's equation and maximum shortening velocity (Vmax) computed. No difference in Vmax was found at 0.75 lo (WKY: 0.048 +/- 0.005; SHR: 0.042 +/- 0.006 lo/s, n = 6 for both). At 0.85 lo, the data were corrected for passive tension (40% to total). Vmax at 0.85 lo was 0.071 +/- 0.009 lo/s (n = 5) for WKY, and 0.069 +/- 0.007 lo/s (n = 5) for SHR. Similar Vmax and force per cell cross-sectional area suggest similar characteristics of actomyosin interaction in SHR and WKY aorta.

Animals↗

Length-tension relations of smooth muscle from normal and denervated rat urinary bladders.

Urinary bladders of rats were denervated by bilateral excision of the pelvic ganglion and removed 10 days after the operation. They were filled with 0.75 ml saline and a longitudinal muscle strip was marked out, measured and dissected out. Strips from normal bladders filled with the same volume were used as controls. Denervated bladders were 4-5 times heavier than control bladders. Muscle strips from denervated bladders showed, in contrast to controls, marked phasic spontaneous contractions which were unaffected by tetrodotoxin, indicating a myogenic origin. Active tension in response to AC stimulation was measured at different lengths. In relation to the in situ length (Lin situ) at 0.75 ml the denervated strips had to be stretched to much greater extent than controls in order to reach optimum length (L0) for force development. Furthermore, the denervated strips shortened less in relation to Lin situ than the controls. If active length-tension relations were expressed in relation to L0, the difference between denervated and control strips was abolished. Maximal active force was the same for denervated and control strips. Water content increased significantly in denervated bladders. The results suggest a remodelling of the smooth muscle structure in denervated bladders; the characteristics of the contractile machinery seem, however, to be unaltered.

Animals↗

Structural and mechanical alterations in hypertrophic venous smooth muscle.

Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days the transluminal pressure of the portal vein was measured, and the vessel was fixed in situ for electron-microscopy, or dissected out and mounted in an apparatus recording force and shortening. Portal veins from sham-operated animals were used as controls. Portal venous pressure had increased about twofold after the partial ligation and the cross-sectional area of the longitudinal muscle layer about twofold. Number of muscle cells per mm2 cross-sectional area decreased to half of the control value, whereas extracellular space in the muscle layer and the dry weight of the preparations were unaltered. Number of cells was unchanged suggesting that no hyperplasia had occurred. Length-passive force relations were shifted towards higher force values in the hypertrophic vessels, whereas passive stress-strain characteristics were similar. The structures that carry passive tension have thus increased in proportion to the vessel as a whole. Length-active tension curves obtained by stimulation with AC current or high K+ solutions indicated that the hypertrophic vessels could not, in relation to optimal length for active force, shorten to the same extent as control vessels. Maximum active tension per vessel was unaltered whereas force per unit muscle area and force per cell had decreased. As the preparations were supramaximally stimulated and had optimal extracellular Ca2+ concentrations we suggest that the amount of functional contractile proteins has not increased in proportion to the increase in size of the muscle cells.

Animals↗

Stimulatory effects of Ba2+ on contractile activity in the smooth muscle of the rat portal vein.

The effects on mechanical activity in rat portal vein of adding Ba2+, Sr2+ or Mg2+ (0.3--10 mM) to a tris-buffered solution (Na-tris) with 2.5 mM Ca2+ was investigated and compared to the effects of addition of Ca2+. Ba2+ induced a continuous tetanical activity and increased integrated force from threshold (0.3 mM) to sevenfold (10 mM). Addition of Sr2+ and Ca2+ had only minor effects on mechanical activity, whereas Mg2+ in increasing concentrations exerted an inhibitory effect. Contractures were elicited in K+-high tris solution with 2.5 mM Ca2+. The amplitudes of the contractures were not affected by added Mg2+, whereas Ca2+, Sr2+, and Ba2+ increased contracture force to some extent, the increase being highest for Ba2+ (twofold in 10 mM). Sucrose gap recordings of electrical and mechanical activity showed that added Ba2+ (0.3 mM) to Na-tris with 2.5 mM Ca2+ increased spike discharge and force/spike, the latter almost twofold. A corresponding addition of 0.3 mM Ca2+ had no effect. The effects of adding Sr2+ are very similar to that of added Ca2+, Mg2+ decreased spontaneous mechanical activity. Relaxation rates after K-contractures with 2.5 mM Ca2+, Ba2+, or Sr2+ were determined. No difference was found after K-tris with Ca2+ or Ba2+, whereas the veins relaxed faster after K-tris with Sr2+. We conclude tht Ba2+ acts as a constrictor of the smooth muscle in rat portal vein partly by initiating an increased spike discharge, and partly by increasing the entry or release of Ca2+ per spike, whereas the removal of Ca2+ is unaffected.

Animals↗

Oxygen dependence and energy turnover in normal and hypertrophic rat portal vein.

Oxygen consumption (Jo2), lactate production (JLA), and active force were studied on rat portal veins that had hypertrophied in response to a 5 days period of increased transmural pressure. The vessels were mounted in vitro at optimum lengths for force development. The walls of the hypertrophic (H) veins had in comparison to their controls (C) an increased cross-sectional area (1.14 +/- 0.05 vs. 0.46 +/- 0.03 mm2, S.E., n = 12). The H veins had a diminished or absent spontaneous contractile activity in contrast to C. The influence of surrounding Po2 on amplitude of K+-induced contractures was studied in an open organ bath. For both C and H veins a decline in force was seen at Po2 levels around 275 mmHg and below. Energy metabolism was studied in a closed glass chamber (volume 1.2 ml) at a Po2 of 290 mmHg. In comparison to recordings at 690 mmHg. JLA and active force were unaltered in both groups indicating a sufficient O2 supply. For veins relaxed in Ca2+-free solution Jo2 and JLA were higher in H veins compared to C if expressed per unit vessel length (Jo2:0.47 +/- 0.03 vs. 0.20 +/- 0.02, JLA:0.66 +/- 0.09 vs. 0.22 +/- 0.03 nmol/min x mm, n = 6). When the comparisons were made per unit weight Jo2 was similar, about 0.38 mumol/min x g whereas JLA was higher in the H group (0.53 +/- 0.04 vs. 0.38 +/- 0.05 mumol/min x g). Contractures were elicited in high-K+ solutions with varied amounts of Ca2+ added. Maximal force per unit areas was lower for H veins compared to C (9.5 +/- 1.6 vs. 16.3 +/- 3.3 mN/mm2). For both groups Jo2 increased with active force. JLA increased with force for C but was unaltered for H veins. The relation between calculated ATP production and force was less steep for H indicating a lower metabolic tension cost.

Adenosine Triphosphate↗