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Biomedical subjects

W Osswald

Publications and source records attributed to W Osswald.

At least 37 records · Page 2Linked to original sources
PubMed1991

Diosmin therapy alters the in vitro metabolism of noradrenaline by the varicose human saphenous vein.

We have previously shown that diosmin 30-100 mumol/l reduces the metabolism of noradrenaline (NA) in fragments of varicose saphenous veins obtained at surgery. Since diosmin is widely used in patients with chronic venous insufficiency we decided to test if the drug, administered in therapeutic doses to patients, would affect NA metabolism in the veins of the individuals so treated. Sex- and age-matched patients in which surgery was indicated were allocated in the order of admission to control (n = 5) or treated groups (n = 6; 600 mg twice a day, orally, during 10 days). Fragments of saphenous vein were incubated with [3H]NA 0.2 mumol/l during 60 min; the interval between operation and incubation was less than 30 min. Column chromatography and liquid scintillation counting were used to measure [3H]NA and its metabolites. In the treated group, accumulation of [3H]NA was significantly reduced and the formation of metabolites approximately halved. The present results show that oral administration of diosmin has evident effects on the in vitro metabolism of noradrenaline by the varicose tissue.

Administration, Oral↗
PubMed1991

Air pollution: involvement of oxygen radicals (a mini review).

In the past decades air pollution has increased worldwide. We also gained more insight into the complex interactions between different air pollutants in the atmosphere as well as their effects on living cells and organisms. It also has been unequivocally shown by several groups in different countries that oxy radicals play an outstanding role in the interconversion of air pollutants as well as during the manifestation of toxic effects. Not only living systems are affected by air pollutants, but also inorganic systems such as buildings and sculptures. In the following overview the most important reactions occurring in the atmosphere as well as effects of oxidative gaseous compounds and particles such as diesel soot and asbestos will be discussed.

Air Pollutants↗
PubMed1990

Purine agonists prevent trophic changes caused by sympathetic denervation.

Surgical denervation of the lateral saphenous vein of the dog causes marked extraneuronal changes, both of a morphological and functional type. In an attempt to investigate the factor(s) responsible for the trophic effects exerted by the sympathetic innervation on the dog saphenous vein we studied the effects of noradrenaline, adenosine, inosine and N-ethylcarboxamidoadenosine (NECA) on vascular tissue after sympathetic denervation. The saphenous vein was denervated using either surgical or chemical (6-hydroxydopamine, 6-OHDA) methods. Noradrenaline (0.1 microgram/kg per h), adenosine (10 micrograms/kg per h), inosine (10 micrograms/kg per h) or NECA (0.1 microgram/kg per h) were delivered continuously for 5 days through Alzet minipumps connected to the vein. 6-OHDA-induced denervation resulted in morphological changes similar to those described for surgical denervation. Smooth muscle cells and fibroblasts showed ultrastructural signs of increased synthetic activity and their size was significantly increased. In confirmation of earlier studies, constant i.v. infusions of noradrenaline did not prevent the morphological changes induced by denervation. Adenosine prevented the morphological changes induced by chemical or surgical denervation. Similarly to adenosine, infused NECA prevented the structural consequences of denervation. In contrast, inosine did not prevent the changes caused by surgical denervation. The results are compatible with an involvement of purines in the trophic effects of sympathetic innervation. Moreover, the effects of adenosine do not appear to be mediated by inosine.

Adenosine↗
PubMed1990

Oxidative deamination of noradrenaline in human blood vessels.

Human vascular tissue (saphenous vein and uterine artery) was incubated with tritiated noradrenaline. In both vessels, oxidative deamination predominated over O-methylation. Deamination was due to the action of MAO type A and B, as well as of a semicarbazide-sensitive oxidase. Whereas DOPEG was a good index of intraneuronal deamination, NMN, DOMA and OMDA appeared to be entirely extraneuronal in origin. Extraneuronal deamination plays an important role in human vascular tissue and may contribute to the inactivation of circulating catecholamines.

Arteries↗
PubMed1989

Sympathetic denervation caused by long-term noradrenaline infusions; prevention by desipramine and superoxide dismutase.

1. The effects of continuous intravenous infusion of noradrenaline (0.01 and 0.1 microgram kg-1 h-1) were studied in both the infused lateral saphenous vein and the contralateral saphenous vein of normal dogs. Noradrenaline, saline, noradrenaline + desipramine or noradrenaline + superoxide dismutase were infused using Alzet osmotic minipumps. 2. After a 5 day infusion period, the noradrenaline content in plasma and in both saphenous veins was determined, and the venous tissues submitted to light microscope morphometry and ultrastructural study and used for the determination of their O-methylation capacity (with [3H]-isoprenaline as a substrate). 3. Noradrenaline caused dose-dependent damage to the sympathetic nerve endings of the lateral saphenous veins. Concomitant changes in extraneuronal structure and function were observed (hypertrophy of smooth muscle cells, nuclear dysmorphy, thickening of the vessel wall, impairment in O-methylation capacity). 4. Desipramine and superoxide dismutase prevented or reduced the effects of noradrenaline on both the morphological and the biochemical parameters; the protection afforded by superoxide dismutase was more marked than that by desipramine. 5. It is concluded that moderately high doses of noradrenaline exert a 6-hydroxydopamine-like effect and that this chemical sympathectomy is partially or totally prevented by desipramine or superoxide dismutase. The data suggest that a substance derived from noradrenaline, in the formation of which free oxygen radicals are involved and which is subject to neuronal uptake, is the chemical entity responsible for the neurotoxic effect observed.

Animals↗
PubMed1988

The actions of 5-hydroxytryptamine receptor agonists and antagonists at pre- and postjunctional level on the canine saphenous vein.

The prejunctional and postjunctional 5-HT receptors of the canine saphenous vein were studied. The release of 3H-noradrenaline (3H-NA) from incubated saphenous vein strips was inhibited by 5-hydroxytryptamine (5-HT) in a concentration-dependent way (5-HT concentrations: 0.01, 0.1 and 1.0 mumol.l-1), but not by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 1 and 10 mumol.l-1). The inhibitory effect of 5-HT was antagonized by metitepine and methysergide, but not by yohimbine, (-)-pindolol or ketanserin. In strips preincubated with 5-HT (1.2 mumol.l-1), the fractional release of 3H-NA was slightly reduced (paired experiments). 5-HT and 8-OH-DPAT caused concentration-dependent contractions of the saphenous smooth muscle. A parallel shift of the concentration-response curve for 8-OH-DPAT to the right was caused by metitepine and yohimbine, but not by ketanserin. The contractions caused by 5-HT were antagonized by metitepine and yohimbine (parallel displacement of the curves to the right), as well as by ketanserin and methysergide (with a depression of the upper part of the curve). Blockade of alpha-adrenoceptors (due to prazosin plus a low concentration of yohimbine) also resulted in a weak antagonistic effect. Ketanserin and metitepine displaced the noradrenaline concentration-response curve to the right. We conclude that the saphenous vein of the dog is endowed with prejunctional receptors of the 5-HT1 type which can not be classified as belonging either to the 1A or 1B subtype; and that at the postjunctional level 5-HT1 (possibly of the 1D subtype) and 5-HT2 receptors are present.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Spontaneous and ouabain-induced efflux of catecholamines and dihydroxyphenylglycol in two canine blood vessels.

The spontaneous efflux of endogenous noradrenaline, dopamine, dihydroxyphenylglycol (DOPEG) from adrenergic nerve endings of 2 canine blood vessels (the mesenteric artery and the saphenous vein) were studied during 8 successive incubation periods of 15 min each. Extraneuronal uptake and O-methylation were minimized by the presence of adequate concentrations of tropolone and hydrocortisone. Both vessels had an efflux characterized by a decline in the 3 catechols, which was most marked for noradrenaline; the mesenteric artery lost larger amounts than the saphenous vein. Ouabain caused a large increase in the efflux of noradrenaline and dopamine and a reduction of DOPEG efflux. Cocaine had only a modest effect, more evident in the case of the mesenteric artery, increasing noradrenaline and reducing DOPEG effluxes. The combination of ouabain and cocaine had no additive effects, and the effects of ouabain were even reduced (on some parameters) by cocaine. Accordingly, the noradrenaline:DOPEG ratio was markedly increased by ouabain, but not by cocaine; cocaine significantly reduced the effects of ouabain. The ratio dopamine:noradrenaline was decreased by cocaine and by ouabain. Comparison of tissue content and efflux allowed us to conclude that apparently no significant de novo synthesis of noradrenaline occurred during the incubation period. We conclude that a fast and early component of spontaneous efflux is due to loss from the neurons and that its greater magnitude in the mesenteric artery may be due to differences in neuronal [Na+] and/or to differences in neuronal membrane adenosine triphosphatase activity. The results also suggest that neuronal reuptake plays only a minor role in the handling of spontaneously released noradrenaline.

Animals↗
PubMed1985

Effects of a monoamine oxidase A inhibitor, FLA 668 (+) on the adrenergic mechanisms of the dog saphenous vein.

FLA 668 (+) [(S)-(+)-4-amino-2, alpha-dimethylethylphenethylamine (+)-hydrogen bitartrate] selectively inhibited MAO type A in homogenates of dog saphenous vein, with a IC50 of 1 mumol/l for MAO A and greater than 1 mmol/l for MAO B. At concentrations of 1 mumol/l and higher, FLA 668(+) progressively decreased the formation of deaminated metabolites by saphenous vein strips incubated with 3H-noradrenaline, with a preferential action on DOPEG formation. Normetanephrine formation increased but this increase did not wholly compensate for the reduction in the formation of deaminated metabolites. FLA 668(+) caused increased reactivity of saphenous vein strips to noradrenaline and markedly reduced the accumulation of 3H-noradrenaline in the incubated tissue; both effects were still evident in the presence of clorgyline. After cocaine, FLA 668(+) caused no further increase in sensitivity. It is concluded that FLA 668(+) is, in the saphenous vein of the dog, a selective inhibitor of MAO type A and that it exerts a cocaine-like effect.

Animals↗
PubMed1985

Effects of clorgyline and (-)deprenyl on the deamination of normetanephrine and noradrenaline in strips and homogenates of the canine saphenous vein.

The influence of specific inhibitors of MAO A (clorgyline) and MAO B [(-)deprenyl] on the metabolism of normetanephrine (NMN) in strips of canine saphenous vein was studied, both in the absence and in the presence of inhibitors of neuronal (cocaine) and extraneuronal (hydrocortisone) uptake. Moreover, the formation of metabolites of noradrenaline and of NMN by saphenous vein homogenates and the influence of clorgyline or (-)deprenyl on this formation are described. Clorgyline reduced to the same degree (by about 70%) the formation of methoxy-hydroxy-phenylglycol (MOPEG) and of vanillylmandelic acid (VMA) in strips incubated with NMN, whereas (-)deprenyl reduced by about 50% the formation of MOPEG and had no effect on VMA production. Hydrocortisone had effects very similar to those of (-)deprenyl. Saphenous vein homogenates (O-methylation inhibited), deaminated both noradrenaline and NMN; clorgyline and (-)deprenyl reduced the formation of metabolites of both noradrenaline and NMN. It is concluded that both MAO A and B are able to deaminate noradrenaline and NMN, but that in the intact tissue the former has no access to MAO B. Even in intact tissues MAO B may play a role in the metabolism (but not in the inactivation) of noradrenaline by deaminating the NMN formed from noradrenaline and giving preferentially origin to MOPEG.

Animals↗
PubMed1985

Effects of two venotropic drugs on inactivation and O-methylation of catecholamines in an isolated canine vein.

Clobenoside (1-O-ethyl-3-O-propyl-5,6-di-O-chlorbenzyl-D-glucofuranose, CL) and Venoruton [O-(beta-hydroxyethyl)-rutosides, HR] did not cause supersensitivity to either exogenous or endogenous (stimulation-released) noradrenaline, in strips of the saphenous vein of the dog. Both drugs caused a significant blockade of the inactivation of noradrenaline, in oil immersion experiments. In incubation experiments with 3H-isoprenaline, CL and HR (100 to 900 mumol/l) caused a dose-dependent inhibition of O-methylation; they had additive effects with the COMT inhibitor, U-0521 and their effects were abolished in the presence of hydrocortisone. In incubation experiments with 3H-adrenaline, formation of metanephrine was inhibited, neuronal uptake and oxidative deamination remaining unaffected. After intravenous administration of HR (100 mg/kg), the O-methylating capacity of blood vessels was similarly reduced. It is concluded that CL and HR affected exclusively the extraneuronal O-methylating system (probably both by inhibiting COMT and depressing uptake) and that this effect may contribute to their therapeutic actions.

Animals↗
PubMed1984

Structural and functional alterations caused at the extraneuronal level by sympathetic denervation of blood vessels.

The lateral saphenous vein of the dog and the rabbit ear artery were surgically denervated, by clamping the vessel or by removal of the superior cervical ganglion, respectively. Both procedures resulted in denervation of the vessels. The denervated, lateral saphenous vein was supersensitive to exogenous noradrenaline and inactivation of the amine (in oil immersion experiments) was slower in denervated vein strips than in control strips treated with cocaine. Incubation experiments with 3H-noradrenaline confirmed that denervated strips formed considerably fewer metabolites than control ones (in the absence or presence of cocaine) and that O-methylation of noradrenaline was reduced by about 50%. When the strips were incubated with 3H-isoprenaline, the denervated ones accumulated and metabolized isoprenaline to a lesser degree than control strips. Hydrocortisone did not reduce the accumulation of isoprenaline in the denervated vein and had only minor effects on O-methylation. The metabolism of noradrenaline and isoprenaline gradually recovered with time. In the ear artery, denervation was accompanied by a marked reduction in O-methylation, but not in accumulation, of isoprenaline. In both vessels there was a highly significant positive correlation between noradrenaline content and O-methylating capacity; in the saphenous vein accumulation of isoprenaline was also positively correlated to noradrenaline content. Morphological changes observed in the denervated vessels consisted essentially in dedifferentiation of smooth muscle cells (which attained larger dimensions, had an indented, large nucleus, augmented euchromatin and an increased amount of ribosomes), abundance of extracellular material and fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Intra- and extraneuronal metabolism of 5-hydroxytryptamine in the isolated saphenous vein of the dog.

The uptake and metabolism of 3H-5-hydroxytryptamine (5-HT) in the isolated saphenous vein of the dog was studied, as well as the sensitivity to 5-HT and its termination of action (as determined by oil immersion experiments). After exposure of the vein to 0.23 mumol/1 5-HT for 30 min, about one half of the 5-HT removed was accumulated in the tissue, the other half appearing in the form of metabolites. Cocaine, chlorimipramine or denervation reduced the accumulation, but not the metabolism, of 5-HT; hydrocortisone reduced both accumulation and metabolism. Hydrocortisone plus cocaine (or phenoxybenzamine alone) caused a greater reduction of accumulation and metabolism than hydrocortisone or cocaine alone. Pargyline caused an increase in accumulation and virtually abolished metabolism; amezinium also abolished metabolism, but reduced accumulation (the same effects as caused by cocaine plus pargyline). Cocaine (12 mumol/l) caused supersensitivity to 5-HT and a prolongation of the half-time for relaxation in oil; hydrocortisone (40 mumol/l) had no effect on sensitivity, but prolonged somewhat the half-time for relaxation in oil, showing supra-additive effects with cocaine. 5-HT, taken up into adrenergic nerve terminals, was released by electrical stimulation; no appreciable reduction in fractional release occurred during repeated stimulations. Exposure to cocaine prior to incubation with 5-HT prevented the neuronal uptake of 5-HT. Compartmental analysis, done with the help of washout curves of strips pretreated with pargyline and loaded with 3H-5-HT, shows that 3H-5-HT distributed into 3 compartments plus a bound fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

On the mechanism of action of amezinium methylsulphate on the dog saphenous vein.

Strips of dog saphenous vein were used to study the multiple effects of amezinium methylsulphate (AM) on adrenergic mechanisms. The ED50 of the contractile effect was 0.55 microM. After the maximal response to AM had been obtained, increasing the concentration of AM resulted in relaxation; a larger contraction occurred after washout. AM was not able to cause contraction of strips obtained from dogs pretreated with reserpine; phentolamine shifted the dose-response curve of AM to the right. AM 0.1 and 10 microM enhanced the sensitivity of the strips to noradrenaline (NA) about 3.5 and 11 times respectively. When the cocaine-like effect was excluded (by using cocaine itself, either alone or after pretreatment with reserpine) an alpha blocking effect of AM was demonstrated at a concentration of 100 to 150 microM. In homogenates from venous tissue, AM inhibited monoamine oxidase (MAO) activity. AM inhibited preferentially MAO type A, since the IC50 was 5 microM for MAO A and greater than 1 mM for MAO B. In the intact tissue, AM 0.01 microM reduced the formation of [3H]dihydroxyphenylglycol [3H ]DOPEG) without significantly altering the accumulation of [3H]NA or the formation of the other metabolites. AM 0.1 microM reduced the accumulation of NA, and AM 10 microM abolished the accumulation of [3H]NA, reduced the formation of deaminated metabolites and enhanced the formation of [3H]normetanephrine [3H ]NMN). In washout experiments of strips preloaded with [3H]NA, AM enhanced the efflux of [3H]NA and the effect began with 1 microM; washout of AM sustained the efflux of [3H]NA for at least 30 min. The deaminated metabolite [3H]DOPEG was significantly decreased.

Animals↗
PubMed1983

Autoradiographic study of rat hearts perfused with 3H-isoprenaline.

Bönisch et al. (1974) identified kinetically two extraneuronal compartments into which 3H-isoprenaline distributes in the perfused rat heart: compartment III (characterized by a half time for the efflux of 3H-isoprenaline of about 10 min) had about the same size as compartment IV (half time for efflux: 23 min). These authors suggested that compartment III might be located in the vascular smooth muscle, while compartment IV might be located in myocardial cells. The present study was carried out to validate or refute this suggestion. Rat hearts were perfused for 5, 20 or 60 min with 1 mumol/l 3H-isoprenaline; additional hearts were perfused with 1 mumol/l 3H-isoprenaline for 30 min in the presence of either 20 mumol/l corticosterone or 20 mumol/l corticosterone plus 30 mumol/l cocaine. COMT was inhibited in all experiments (by the presence of 100 mumol/l U-0521). Quantitative autoradiography revealed in all groups that the silver grain density (grains/mm2) was greater over small blood vessels (arterioles and venules) than over myocardial cells. However, total silver grains over myocardial cells greatly exceeded those over small blood vessels (by a factor of 6 to 9). Thus, the suggestion of Bönisch et al. (1974) is untenable. Autoradiographic results obtained with small specimens of ventricular muscle are representative of the whole heart, since "silver grains over total tissue" (per mm2) were highly significantly correlated with the 3H-isoprenaline content of the homogenized hearts (in pmol/g). While corticosterone reduced the accumulation of 3H-isoprenaline in myocardial cells, it failed to affect the appearance of silver grains over Purkinje cells. However, cocaine prevented this type of accumulation. Thus, uptake in Purkinje cells appears to resemble neuronal rather than extraneuronal uptake.

Animals↗