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Biomedical subjects

K Magyar

Publications and source records attributed to K Magyar.

At least 91 records · Page 5Linked to original sources
PubMed1988

Relaxation by prostacyclin (PGI2) of human, dog and rabbit femoral artery strips. Interspecies difference.

Helically cut femoral artery strips from humans (bypass surgery), dogs and rabbit were set up for isometric recording. The endothelial layer was removed by rubbing, hence the vascular strips used in this study are considered to be arterial smooth muscle preparations without endothelium. The indomethacin-, prostaglandin F2 alpha- and PGI2-induced changes in tone were determined. Indomethacin (3/mumol/l) potentiated the contractile responses of human and canine vessels to PGF2 alpha by 60.0 +/- 10.4 and 108 +/- 12%, respectively. By contrast, the PGF2 alpha-induced contractions of rabbit arteries were not enhanced by the cyclooxygenase inhibitor. PGI2 diminished the tone of the PGF2 alpha-contracted vessels obtained from all the three species in a concentration-related manner. The potency of the relaxant prostanoid differed, however, markedly (p less than 0.02) from species to species. The IC50 values (molar concentrations of PGI2 producing 50 percent reduction in the PGF2 alpha-induced tone) were 20.8 +/- 1.9, 133 +/- 24 and 286 +/- 52 nmol/l for human, dog and rabbit arteries, respectively. The results clearly demonstrate a significant interspecies difference in the prostacyclin-sensitivity of the blood vessels studied. The differential responsiveness to indomethacin may reflect species-difference in the regulatory function of PGI2 in arterial smooth muscle tone.

Animals↗
PubMed1988

Actions of PGE2 and indomethacin on adrenergic neuroeffector transmission in the rabbit coeliac artery.

In the present study we have investigated the pre- and post-synaptic actions of PGE2 and indomethacin on the adrenergic transmission in isolated coeliac arteries of rabbits. The artery segment was preloaded with (3H)NA and suspended in an organ bath (37 degrees C, 5% CO2 - 95% O2, isometric recording). The preparation was superfused with Krebs-solution containing the uptake blockers cocaine and corticosterone. To release neurotransmitter, the artery was stimulated by electrical square-wave pulses (0.5 ms, 5 Hz, 60 s) using platinum wire electrodes. The perfusate was collected in 3 or 6 min samples. The outflow of labelled neurotransmitter was expressed in pmol/3 min. Inhibition of endogenous prostaglandin-biosynthesis by indomethacin (3/mumol/l) potentiated the contractile responses to nerve stimulation (57 +/- 15%, n = 4), but did not influence the release of NA (the release ratio was 1.02 +/- 0.03, n = 4). The endogenous prostaglandins may modulate vascular neuroeffector transmission postjunctionally, because cyclooxygenase inhibition did not cause any change in transmitter release. The effects of exogenous PGE2 on adrenergic transmission and contraction were also studied. In this case, indomethacin was present to minimize the potential complicating actions of endogenous prostanoids. At low concentrations (1, 3 and 10 nmol/l) PGE2 dose-dependently inhibited vasoconstrictor responses to nerve stimulation (IC50 = 4.7 +/- 1.5 nmol/l, n = 4), but was ineffective in influencing transmitter release (the stimulation evoked release ratios were 0.95 +/- 0.05, 1.00 +/- 0.00 and 0.93 +/- 0.11, n = 4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Stimulation of hypothalamic histidine decarboxylase by calcium-calmodulin and protein kinase (cAMP-dependent) inhibitor.

Stimulatory effects of Ca2+-CaM and PKI on partially purified hypothalamic HD (10 fold purification) have been shown under conditions involving inhibition of the enzyme by cAMP-induced phosphorylation and under control conditions. A 1:1 (v/v) mixture of 0.1 mM CaCl2 and 10 units of CaM from human red blood cells reversed the inhibition of HD induced by cAMP-dependent protein phosphorylation activity to the control level. Verapamil (0.01 mM) could partially block the former effect without affecting the control level of enzyme activity. 0.01 mM TPA did not further increase the effect of Ca2+-CaM on HD, in the presence of 0.01 mM ATP, indicating that this stimulation does not require the action of Ca2+-dependent protein kinase. The control level of HD is not influenced by 0.1 mM CaCl2 or 0.02 mM EGTA but is raised by CaM in the presence of CaCl2 (0.1 mM). A highly purified protein kinase (cAMP-dependent) inhibitor (PKI) from bovine heart and a crude inhibitor from rat cerebellum could also reverse the inhibitory effect of cAMP-dependent protein kinase under phosphorylating conditions and enhanced HD activity above control levels. PKI and Ca2+-CaM, added together, produced single, not additive effects. We conclude that cAMP-induced phosphorylation is probable the main regulatory mechanism of histamine formation and this could be influenced by both Ca2+-CaM and PKI. Inhibition of cAMP-dependent protein kinase as well as stimulation of phosphoprotein phosphatase and Ca2+-CaM-dependent phosphodiesterase might be involved in the above actions.

Animals↗
PubMed1987

Inhibition by quinine of endothelium-dependent relaxation of rabbit aortic strips.

1 The effects of quinine sulphate, tetramethylammonium chloride (TMA) and tetraethylammonium chloride (TEA) (all blockers of the Ca2+-activated K+ channels) on the relaxations induced by acetylcholine (ACh), calcium ionophore A23187 and sodium nitrite were studied in helical strips of rabbit aorta. 2 The strips were contracted to a moderate stable tone with phenylephrine (10(-7) M). ACh (4 X 10(-9) to 10(-6) M) as well as A23187 (10(-8) to 3 X 10(-7) M) reduced this tone in a concentration- and endothelium-dependent manner. 3 Pretreatment of the tissues with quinine (2.5 X 10(-5) to 10(-4) M) for 60 min produced a concentration-dependent inhibition of the relaxation induced by ACh. Also 90 min incubation of the strips with TMA (3 X 10(-3) to 6.5 X 10(-2) M) or TEA (10(-3) to 3 X 10(-2) M) inhibited the ACh-evoked relaxation in a manner similar to quinine. 4 Quinine (10(-4) M, 60 min), TMA (6.5 X 10(-2) M, 90 min) or TEA (3 X 10(-2) M, 90 min) produced 5 to 10 fold reductions in the relaxant EC50 values of A23187 and ACh and depressed (by 40 to 95%) the maximal relaxations to the ionophore and ACh. 5. On a molar basis, quinine was more effective than the two tetraalkylammonium ions in reducing the endothelium-dependent relaxations of the aortic strips induced by ACh or A23187. The inhibitory actions were reversible after 60 to 90 min washout. 6. Exposure of the strips to either quinine (10-4M, 60 min), TMA (6.5 x 10-2 M, 90 min) or TEA (3 X 10-2 M, 90 min), however, did not influence significantly the relaxations evoked by sodium nitrite, a direct smooth muscle relaxant. 7. These results suggest that stimulation of the Ca2+-activated K' channels could be, at least partially, responsible for the endothelium-dependent relaxations induced by ACh or A23 187. Their activation might not be required for the endothelium-independent relaxant effects of sodium nitrite.

4-Aminopyridine↗
PubMed1987

Transmitter releasing action of selegiline ((-)-deprenyl) from peripheral sympathetic nerves under different experimental conditions.

A high concentration of selegiline ((-)-deprenyl; 10(-4) M) potentiated low frequency (2 Hz) nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers, and inhibited the postsynaptic response. The transmitter-releasing action of 10(-4) M selegiline was inhibited by a moderate increase of external K+ (23.6 mM). Excess K+ by itself abolished the nerve-evoked release of [3H]noradrenaline but did not increase the resting outflow of radioactivity. Excess Ca2+ (7.5 mM) increased the stimulation-evoked transmitter release. In the presence of excess Ca2+, selegiline (10(-4) M) was effective in increasing the [3H]noradrenaline release in response to nerve-stimulation. Excess Ca2+ partly antagonized the postsynaptic inhibitory action of selegiline. In Ca2+-free, 1 mM EGTA-containing Krebs solution both the nerve-evoked 3H release and the transmitter releasing action of selegiline were abolished in agreement with the 'Ca-hypothesis'. The voltage-dependent K+-channel blocker, 4-aminopyridine (10(-5) M), increased the nerve-stimulation-evoked release of tritium from arteries. If selegiline was also present in the perfusion medium the nerve-evoked transmitter release further increased. 4-Aminopyridine completely antagonized the inhibitory action of selegiline on the postsynaptic contraction.

Animals↗
PubMed1987

[3H]noradrenaline release from rabbit pulmonary artery: sodium-pump-dependent sodium-calcium exchange.

1. The release of [3H]noradrenaline ([3H]NA) from the isolated main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers. 2. K+ removal from the external medium increased the release of [3H]NA, an action transiently inhibited by Ca2+-free (+1 mM-EGTA) solution, i.e. after Ca2+ removal transmitter release was first abolished and then started to increase again after a delay lasting about 90-120 min. 3. Ca2+ readmission to arteries which had been kept in Ca2+- and 'K+-free' solution, markedly increased the [3H]NA release. The rate of transmitter release was dependent on the preceding perfusion period with 'K+-free' solution, being greater for longer exposure times. 4. When Ca2+ and K+ were readmitted together to K+-depleted and Na+-enriched preparations, the release of [3H]NA transiently increased. 5. If K+ was readmitted first, the subsequently applied Ca2+ was ineffective in producing transmitter release. 6. Different alkali metal ions (Rb+, Cs+ or Li+) were also readmitted as K+ substitutes together with Ca2+. In all cases the release of neurotransmitter transiently increased; however, the rate of release was dependent on the monovalent cation used. Thus, Rb+ ions were as effective as, Cs+ about one-third as effective as, and Li+ about one-fifth as effective as K+ in activating the Na+ pump. 7. It is concluded that in the absence of external Ca2+, and in response to Na+-pump inhibition, the release of Ca2+ from internal stores is responsible for the NA release observed. On readmission of Ca2+ the rate of transmitter release is dependent on the Na+ previously gained inside. Furthermore, the activity of the Na+ pump determines the rate of transmitter release through the Na-Ca exchange mechanism.

Animals↗
PubMed1987

Differential contractile responsiveness of femoral arteries from healthy and diabetic dogs: role of endothelium.

Phenylephrine-induced contraction and acetylcholine-induced relaxation of isolated femoral arterial strips (with and without endothelium) of diabetic (alloxan-treated) and metabolically healthy dogs were determined. Alloxan treatment did not change the contractile responsiveness to phenylephrine (PE) of the arteries with intact endothelium. After mechanical removal of the endothelial layer, however, the maximum force generated by the diabetic vessels (22.0 +/- 2.0 mN.m-2) significantly exceeded the maximum contraction produced by the nondiabetic arteries (14.6 +/- 1.8 mN.m-2). The dose-response curve of diabetic arteries to PE was steeper than it was in non-diabetic strips. The EC50 values for PE were similar in these two groups (0.45 +/- 0.12 and 0.58 +/- 0.20 mumol/l in diabetic and nondiabetic vessels, respectively). In the arteries with intact endothelium, acetylcholine produced concentration-related reduction of PE-induced tone. This endothelium-dependent relaxant activity of acetylcholine was similar in the healthy and diabetic arterial strips, IC50 for acetylcholine being 0.17 +/- 0.02 and 0.20 +/- 0.03 mumol/l, respectively. These results suggest that functional alteration of endothelium (probably an increased release of EDRF) prevails in diabetes. This may be important in reducing the hyper-responsiveness of diabetic arterial smooth muscle to PE.

Animals↗
PubMed1986

Species specificity of thrombin-induced changes in vascular tone.

We studied the effects of acetylcholine and human thrombin on the tone of rabbit and dog isolated femoral arteries and aortas with intact endothelium. Acetylcholine (10(-9)-10(-6) mol/l) produced relaxation in the vessels from both species whereas thrombin (10(-9)-3 X 10(-8) mol/l) relaxed only canine arterial smooth muscle. Thrombin pretreatment increased significantly the relaxant potency of acetylcholine in femoral arteries of dogs. The results suggest an interspecies difference in the thrombin-induced endothelium-dependent vasorelaxation.

Acetylcholine↗
PubMed1986

In vivo measurement of the disaggregatory action of prostacyclin. A methodological study.

The disaggregating effect of PGI2 was measured in a modified in vivo model described by Hornstra. The arterial blood of mongrel dogs was directed through an extracorporeal filter by a roller pump, and the pressure proximal to the filter was measured. The filter became spontaneously occluded mostly by aggregates of platelets within a few minutes, and as a result the pressure before the filter increased continuously. PGI2, administered either before the filter or intravenously, produced dose-related reduction in filtration pressure. Results obtained in control experiments revealed that the rate of platelet aggregation was reproducible; neither the count of platelets in the circulating blood nor the in vitro sensitivity of platelets to ADP and PGI2 changes significantly in the course of an experiment. The technique described seems to be useful to determine the disaggregatory potency of prostacyclin and other substances.

Animals↗
PubMed1986

The action of trelibet, a new antidepressive agent on [3H]noradrenaline release from rabbit pulmonary artery.

Trelibet, a new antidepressant, used at 10(-7)-10(-4) M failed to affect the [3H]noradrenaline ([3H]NA) release evoked from the isolated main pulmonary artery of the rabbit low frequency (2 Hz) nerve stimulation whether the neuronal uptake inhibitor cocaine (3 X 10(-5) M) was present or not. Its metabolite (EGYT-2760) however, potentiated the nerve-evoked release of [3H]NA. In the absence of cocaine both the resting and the stimulation-evoked release of 3H increased in response to EGYT-2760. These effect were accompanied by muscle contraction. The EGYT-2760-potentiated transmitter release was inhibited either by exogenously applied 1-noradrenaline (10(-6) M) or clonidine (10(-6) M), preferential agonists of presynaptic alpha 2-adrenoceptors. The 1-noradrenaline-induced inhibition of transmitter release potentiated by EGYT-2760 was antagonized by 3 X 10(-7) M yohimbine, a preferential alpha 2-adrenoceptor inhibitor. In the absence of cocaine, Ca2+ removal from the external medium failed to affect the 3H outflow-increasing effect of EGYT-2760 but abolished the nerve-evoked release-potentiating action of this compound. It is concluded that the metabolite of trelibet exerts a 'yohimbine-like' action, as well as a 'tyramine-like' effect in peripheral sympathetic nerve fibres.

Animals↗
PubMed1986

Effects of indomethacin, prostaglandins E2 and I2 on the tone of human isolated femoral arteries.

Strips of endothelium-denuded femoral arteries from operated patients were set up for isometric recording. Indomethacin (IND, 3 mumol 1(-1] enhanced basal tension of the arteries from 0.13 +/- 0.04 to 0.86 +/- 0.12 mN (P less than 0.001; n = 16) and potentiated the contractile responses of the strips to noradrenaline (NA); EC50 for NA was 1.5 +/- 0.3 mumol 1(-1) (n = 6) in the absence, and 0.4 +/- 0.07 mumol 1(-1) (n = 6) in the presence of IND (P less than 0.01). PGI2 produced dose-related relaxation in IND-treated vessels, its IC50 being 15.0 +/- 1.3 nmol 1(-1). Low concentrations of PGE2 (0.85-8.5 nmol 1(-1] reduced whereas its higher concentrations (28-85 nmol 1(-1] increased smooth muscle tone in the presence of IND. These results indicate that human femoral arteries--unlike femoral arteries of some laboratory animals--are highly sensitive to cyclooxygenase inhibition as well as to PGI2 and PGE2.

Adult↗
PubMed1986

The action of excess potassium and calcium on ouabain-evoked [3H]-noradrenaline release from the rabbit pulmonary artery.

[3H]-noradrenaline [( 3H]-NA) release from the main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers. Removal of K from the external medium increased the [3H]-NA release. In the absence of external K, ouabain (10(-4) M) further enhanced the neurotransmitter release. The 'K-free' stimulated [3H]-NA release was inhibited by an increase of external Ca (7.5 mM), an action antagonized by ouabain. After preperfusion of the preparations for 30 min with either excess K (23.6 mM) or excess Ca (7.5 mM), the ouabain-stimulated [3H]-NA release was inhibited by about 50%; the rates of inhibition did not differ significantly from each other. However, the characteristic initial delay before ouabain-evoked neurotransmitter release was shortened in excess K, and prolonged in excess Ca-containing solution. When both excess K and Ca were applied together 30 min before ouabain perfusion, the action of ouabain in releasing neurotransmitter was also inhibited but the rate of inhibition did not differ significantly from that seen when K or Ca were applied separately. The action of K in shortening the initial delay was partly antagonized by Ca. Excess Ca antagonized the inhibition of ouabain-stimulated [3H]-NA release caused by excess K when Ca and ouabain were applied together after 30 min preperfusion with excess K-containing solution. Again excess Ca failed to inhibit the ouabain-evoked neurotransmitter release if ouabain and excess K were applied together after excess Ca preperfusion (30 min). In both cases the initial delay of ouabain action was greatly shortened. 6 The results suggest a Na-Ca competition at the external activation site of the nerve terminal sodium-pump similar to that of Na-K competition. Furthermore it seems that there is a sort of K-Ca competition as well, suggested by the finding that excess Ca prevented the inhibition caused by excess K of ouabain-evoked noradrenaline release and vice versa.

Animals↗