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Biomedical subjects

E Dóra

Publications and source records attributed to E Dóra.

At least 19 recordsLinked to original sources
PubMed1992

Effect of small changes in extracellular magnesium concentration on the tone of feline mesenteric arteries: involvement of endothelium.

The aim of this study was to investigate the effect of small alterations in extracellular magnesium concentration on the tone of feline mesenteric arteries and to examine the role of endothelium in these responses. We measured isometrical tension of isolated arterial rings, placed between two stainless steel wires in a tissue chamber containing Krebs-Henseleit solution, aerated with a gas mixture containing 95% O2 and 5% CO2 at 37 degrees C. After precontraction with noradrenaline, a decrease of extracellular magnesium concentration from 1.2 mM to 1.0 and 0.8 mM resulted in sustained relaxations, whereas the elevation of extracellular magnesium from 0.8 mM to 1.2 mM caused an increase in vascular tone when endothelium was intact. The magnesium-withdrawal related dilations were absent in endothelium-denuded vessels and were inhibited by oxyhemoglobin (5 x 10(-6) M) and methylene blue (10(-5) M), suggesting the involvement of endothelium-derived relaxing factor in this vascular response. Nifedipine (5 x 10(-7) M) or dichlorobenzamil (3 x 10(-5) M), however, did not affect the magnesium-deficiency related relaxations. Therefore, in this vascular action of magnesium, nifedipine-sensitive calcium channels or the sodium- calcium antiport system are not involved. We conclude that small alterations in extracellular magnesium concentration, possibly within the physiological range, are able to modify the basal formation and release of EDRF, and thus alter arterial smooth muscle tone in this vascular bed. This endothelium- and magnesium-dependent system appears to be more sensitive than the direct smooth muscle actions of magnesium. The possible physiological and pathophysiological consequences of these observations are discussed.

Animals↗
PubMed1991

Contractile and endothelium-dependent dilatory responses of cerebral arteries at various extracellular magnesium concentrations.

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10(-8)-10(-5) M norepinephrine, were significantly potentiated at low Mg2+ (0.8 mM v. the normal, 1.2 mM). High (1.6 and 2.0 mM) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 10(-8)-10(-5) M acetylcholine were inhibited by high (1.6 and 2.0 mM) Mg2+. Lowering of the Mg2+ concentration to 0.8 mM or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

Acetylcholine↗
PubMed1991

Endothelium-dependent influence of small changes in extracellular magnesium concentration on the tone of feline middle cerebral arteries.

The aim of this study was to investigate the effect of small alterations in the extracellular magnesium concentration on the tone of feline middle cerebral arteries and to examine the role of the endothelium in these responses. We measured the isometric tension of isolated arterial rings placed between two stainless steel wires in a tissue chamber containing Krebs-Henseleit solution aerated with a gas mixture containing 95% O2 and 5% CO2 at 37 degrees C. After precontraction with noradrenaline, a decrease of the extracellular magnesium concentration from 1.2 mM to 1.0 and 0.8 mM resulted in sustained relaxations, whereas elevation of the extracellular magnesium concentration from 0.8 mM to 1.2 mM caused an increase in vascular tone when the endothelium was intact. The magnesium deficiency-related dilations were absent in endothelium-denuded vessels and were inhibited by 5 x 10(-6) M oxyhemoglobin and 10(-5) M methylene blue, suggesting the involvement of an endothelium-derived relaxing factor in this vascular response. However, 5 x 10(-7) M nifedipine or 3 x 10(-5) M dichlorobenzamil did not affect the magnesium deficiency-related relaxations. Therefore, nifedipine-sensitive calcium channels or the sodium/calcium antiport system are not involved in this vascular action of magnesium. We conclude that small alterations in the extracellular magnesium concentration, possibly within the physiological range, are able to modify the basal formation and release of endothelium-derived relaxing factor and thus alter arterial smooth muscle tone in this vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1991

Influence of extracellular magnesium on the contractile and endothelium-dependent dilatory responses of feline mesenteric arteries.

To clarify the effect of extracellular magnesium on the vascular reactivity of feline isolated mesenteric arteries, the effects of slight alterations in the extracellular magnesium concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by noradrenaline 10(-8)-10(-5) M, were not affected in the mesenteric artery at low extracellular magnesium (0.8 mM versus to the normal, 1.2 mM). High (1.6 and 2.0 mM) magnesium exerted a modest inhibitory effect on the contractile responses. This depression of the contraction was accompanied with a significant shift to the right in the EC50 value for noradrenaline. The endothelium-dependent relaxations induced by acetylcholine 10(-8)-10(-5) M, were inhibited by high (1.6 and 2.0 mM) magnesium. Lowering of the extracellular magnesium concentration to 0.8 mM, however, failed to alter the dilatory potency of acetylcholine. The depression of the dilatory responses was also accompanied with a shift to the right in the EC50 values for acetylcholine. The present results show, that contractions and endothelium-dependent relaxations of the mesenteric artery are modulated by the extracellular magnesium asymmetrically: slight magnesium deficiency does not affect these responses, whereas elevation of the concentration of this ion inhibits both processes. Extracellular magnesium probably affects rather the binding of these contractile and endothelium-dependent dilatory agonists to their receptors than the calcium influx into the endothelial- and smooth muscle cells in this vessel.

Acetylcholine↗
PubMed1991

Differential vascular actions of ethanol in feline middle cerebral and mesenteric artery.

The vascular actions of ethanol on feline middle cerebral and mesenteric arteries were investigated in vitro. Ethanol (20-500 mM) caused potent contraction in cerebral arteries, but it contracted the mesenteric arteries only weakly. In the middle cerebral artery (but not in the mesenteric artery) ethanol (300 mM) potentiated the noradrenaline (5.10(-6) M) induced contractions. Antiserum for endothelin (in an appropriate concentration to inhibit endothelin-induced contraction; 0.02 mg/ml) did not inhibit the ethanol-induced contractions. Endothelium-dependent relaxations induced by acetylcholine and ATP were also affected by ethanol (300 mM); in the cerebral artery acetylcholine- but not ATP-induced relaxations, whereas in the mesenteric artery ATP- but not acetylcholine-induced relaxations were inhibited significantly. The results suggest that ethanol causes strong (endothelin-independent) contraction and facilitates the response to noradrenaline in the middle cerebral, but not in the mesenteric artery; and it selectively inhibits endothelium-dependent relaxation. These actions of ethanol may contribute to the development of vascular diseases.

Acetylcholine↗
PubMed1986

Effect of surplus amount of oxygen on the cerebrocortical microcirculatory reactions associated to moderate arterial hypotension.

The aim of the present study was to clarify whether tissue hypoxia is involved in the autoregulatory dilatation of cerebrocortical vessels occurring at moderate arterial hypotension. In order to avoid hypoxia that may occur during arterial hypotension, in one part of the experiments the brain cortices were superfused with oxygen saturated (pO2, approximately 500 mm Hg) artificial cerebrospinal fluid (mock CSF). In the other part of the experiments arterial hypotension was induced without superfusing the brain cortices (closed skull). Mean arterial blood pressure (MABP) was decreased in both experimental groups by bleeding to 75-85 mm Hg for approximately 5 min, then the shed blood was reinfused. Changes in cortical vascular volume (CVV), mean transit time of cortical blood flow (tm), and blood flow (CBF) were measured through a cranial window with a microscope reflectometer. Although CSF pO2 differed markedly between the superfused and nonsuperfused experimental groups, arterial hypotension led to similar changes in CVV and tm in both groups. Due to the proper dilatation of the cerebrocortical arterioles, CBF was not altered by arterial hypotension in either of the groups. These results suggest that the brain cortex does not become hypoxic at moderate arterial hypotension and, consequently, incipient tissue hypoxia has no role in the autoregulatory dilatation of the cerebrocortical arterial network.

Animals↗
PubMed1986

Effect of theophylline treatment on the functional hyperaemic and hypoxic responses of cerebrocortical microcirculation.

The purpose of the present study was to elucidate the importance of extracellular adenosine (ADO) in the regulation of cerebrocortical microcirculation during rest, hypoxia, and brain activation. Cerebrocortical microcirculation and fluorescence of reduced nicotinamide adenine dinucleotide (NADH) were measured by surface fluororeflectometry through a cranial window. Arterial hypoxia and brain activation were produced by respirating the animals with a gas mixture containing 6-7% O2 and by injecting 4-6 mg/kg metrazol into the lingual artery, respectively. These reactions were used as test before and after theophylline (THEO) treatment. In some of the experiments only the cortical area beneath the cranial window was treated with THEO (10(-4) M), in others 2 X 10(-4) mol/kg THEO was injected intraperitoneally. Potency of THEO in antagonizing the cerebral blood flow (CBF) increasing effect of topically applied ADO was also tested. It was found that superfusion of the brain cortex with artificial cerebrospinal fluid (mock CSF) containing 10(-4) M THEO does not alter resting CBF, but inhibits the CBF increasing effect of 10(-6) M and 10(-5) M ADO by approximately 70% and 40%, respectively. Intraperitoneally injected THEO increased CBF by approximately 60%, which has been attributed mostly to its action on the systemic circulation. Under control conditions, arterial hypoxia and epileptic seizures increased CBF by approximately 150% and 300%, respectively. Since neither topical nor systemic THEO treatment altered the vasodilatory and CBF increasing potency of arterial hypoxia and attenuated these effects of epilepsy slightly, it was concluded that extracellular ADO is not a critical factor in the regulation of cerebrocortical microcirculation.

Adenosine↗
PubMed1985

Effect of adenosine and its stabile analogue 2-chloroadenosine on cerebrocortical microcirculation and NAD/NADH redox state.

In the present study, the effects of topically applied adenosine (ADO) and its stabile analogue 2-chloroadenosine (CADO) on cerebrocortical microcirculation and NAD/NADH redox state (oxidized/reduced nicotinamide adenine dinucleotide) were investigated. Vascular volume (CVV), mean transit time of blood flow (tm), blood flow (CBF), and NADH fluorescence of the cat brain cortex were measured through a cranial window with a microscope fluororeflectometer. The reference values of CVV, tm, and CBF, measured in the artificial cerebrospinal fluid (mock CSF) which superfused brain cortex, were regarded as 100%. Adenosine and 2-chloroadenosine, in the concentration range of 10(-6) - 10(-3) M, resulted in concentration-dependent increases in CBF and NAD reduction. 10(-5) M adenosine and 2-chloroadenosine increased CBF by 49.6 +/- 5.6% and 80.4 +/- 10.3%, respectively. At a pharmacologically high concentration (10(-3) M), ADO increased CBF by 164.6 +/- 13.5%, CADO by 333 +/- 44%. At the same time, 10(-3) M ADO and CADO shifted the cortical NAD/NADH redox state by 7.9 +/- 0.4% and 12.4 +/- 0.7%, respectively toward a more reduced state. Our results, concerning the vasodilator potency of adenosine and 2-chloroadenosine, accord with available data in the literature. However, the pronounced NAD reduction obtained with these adenosine nucleosides suggests that, besides an action on vascular adenosine receptors, some other changes, such as increased substrate mobilization and possibly cAMP production, may contribute to the vasodilator effect of adenosine and 2-chloroadenosine.

2-Chloroadenosine↗
PubMed1985

Effect of "flow anoxia" and "non flow anoxia" on the NAD/NADH redox state of the intact brain cortex of the cat.

In the present study, we compared the nicotinamide adenine dinucleotide (NAD) reducing potencies of "flow anoxia" and "non flow anoxia" in the cat brain cortex. In animals anaesthetized with alpha D-glucochloralose "flow anoxia" and "non flow anoxia" were produced by ventilating for 2 and 25 min, respectively, with nitrogen gas. Following "non flow anoxia" the brain cortices of dead animals were superfused with oxygen saturated artificial cerebrospinal fluid (mock CSF), and subsequently with CSF containing various concentrations (10(-3 -10 -1) M) of potassium cyanide. NADH (reduced NAD) fluorescence of the brain cortex was measured through a cranial window with a microscope fluororeflectometer. Ventilating the animals for 2 and 25 min with nitrogen gas increased cortical NADH fluorescence (NAD reduction) by 43.5 +/- 2.8% and 135.3 +/- 6.1%, respectively. Oxygen saturated CSF superfusion of the ischemic brain cortex restored the cortical NAD/NADH redox state to the preanoxic level (oxidation of NADH). 10(-1) M cyanide, applied after superfusion of the brain cortex with oxygen saturated CSF resulted in comparable NAD reduction to that produced by "non flow anoxia". On the basis of these findings it is suggested that "non flow anoxia" leads to much greater cortical NAD reduction than "flow anoxia", because oxygen tension in the cortex may not fall to zero mm Hg during nitrogen anoxia lasting for 2 min. Besides this, a more pronounced substrate mobilization and acidosis may also contribute to the greater NAD reducing potency of "now flow anoxia".(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Further studies on reflectometric monitoring of cerebrocortical microcirculation. Importance of lactate anions in coupling between cerebral blood flow and metabolism.

In order to elucidate the possible role of lactate anions in the coupling between cerebral metabolism and blood flow (CBF), a circumscribed area of the brain cortex of chloralose anaesthetized cats was superfused with various concentrations (1-50 mM) of lithium-(1)-lactate. Cerebrocortical microcirculation (vascular volume, mean transit time, blood flow) and fluorescence of reduced nicotinamide adenine dinucleotide (NADH) were measured with a microscope fluoro-reflectometer. Before carrying out these experiments, the penetration depth of the 366 nm exciting light onto the brain cortex has been determined in vitro in cortical brain slices. In addition, in model experiments we studied the effect of deoxygenation of haemoglobin on intensity of the fluorescence and reflected lights measured at 450 nm and 366 nm, respectively. The in vitro experiments showed that approximately 95% of the exciting light may be absorbed by the 0.24 mm thick superficial layers of the brain cortex. A reasonably good linear relationship (correlation coefficient -0.96) was obtained between the blood content of the samples (blood content was varied between 1000 times and 10 times diluted arterial blood) and the reflectance signal (366 nm), and this relationship was not altered discernibly by 0.1 M sodium sulphite. These results indicate that the reflectance signal, measured at 366 nm in vivo in the intact brain cortex, is a good measure of the changes of cortical blood content, i.e. vascular volume. Topically applied lactate increased cerebrocortical NAD reduction in dependence on the concentration. The lactate-produced increase in NADH fluorescence was probably due to the conversion of lactate to pyruvate by the enzyme lactate dehydrogenase and, hence, the reduction of mitochondrial NAD (substrate effect). Because even 50 mM lactate increased CBF only slightly, by 9.4 +/- 2.5%, our results may rule out the involvement of lactate anions (without concomitant acidosis) in the coupling between cerebral metabolism and blood flow.

Animals↗
PubMed1984

Determinants of brain activation-induced cortical NAD/NADH responses in vivo.

In order to elucidate that which are the factors that may influence the direction of brain activation-induced changes in the redox state of oxidized/reduced nicotinamide adenine dinucleotide (NAD/NADH), the brain cortex was electrically stimulated during arterial hypotension and following reinfusion of the shed blood, during arterial hyper- and hypoxia, and during the second phase of spreading cortical depression (SD). Cerebrocortical NADH fluorescence and vascular volume ( CVV ) of cats, anaesthetized by chloralose, were measured with a microscope fluororeflectometer . Under physiologically normal conditions electrical stimulation resulted in pronounced cortical NAD reduction and increase in CVV . These reactions were not altered by arterial hyperoxia and continuous superfusion of the brain cortex with oxygenated artificial cerebrospinal fluid (mock CSF). Arterial hypotension and SD (in phase II) increased NAD reduction and CVV markedly, and the superimposed electrical stimulation brought about NADH oxidation and greatly depressed CVV responses. Reinfusion of the shed blood did not restore NAD/NADH redox state and CVV to their reference levels, and electrical stimulation under this condition led to NADH oxidation and negligible vascular reactions. Since under physiologically normal conditions electrical activation of the brain cortex resulted in NAD reduction and marked increase in CVV and the magnitude of these reactions were not altered by arterial hyperoxia or by superfusion of the brain cortex with oxygenated CSF, it is very unlikely that the brain cortex became hypoxic during stimulation. Because when the steady NAD/NADH redox state of the brain cortex was shifted toward reduction by arterial hypotension and reinfusion and SD, electrical stimulation led to NADH oxidation, it is suggested that the prestimulatory steady redox state has great importance in determining the direction of NAD/NADH redox reactions evoked by activation of the brain cortex.

Animals↗
PubMed1984

Effect of topical adenosine deaminase treatment on the functional hyperemic and hypoxic responses of cerebrocortical microcirculation.

The purpose of this study was to investigate the possible importance of adenosine in cerebrocortical vasodilatation accompanying brain activation (epileptic seizures and direct electrical stimulation) and hypoxia (arterial hypoxia and cyanide poisoning of the brain cortex). In chloralose-anesthetized cats a circumscribed area of the brain cortex was treated with adenosine deaminase (Type III; Sigma), which potently deaminates adenosine to the nonvasoactive inosine. Cerebrocortical vascular volume and fluorescence of reduced nicotinamide adenine dinucleotide were measured in vivo by surface fluororeflectometry. The responses of small pial and intracortical vessels to brain activation and hypoxia were studied in brain cortices superfused with artificial (mock) CSF and 5 U/ml adenosine deaminase. It was found that superficially applied adenosine deaminase readily diffuses onto the brain cortex. Prolonged pretreatment of the brain cortices with 0.025 U/ml adenosine deaminase eliminated almost completely the vasodilative effect of 10(-7) mol/ml adenosine. The inhibitory effect of the enzyme on adenosine-induced cortical vasodilatation was specific, because 5 U/ml adenosine deaminase did not attenuate the vasodilative potency of 10(-8) mol/ml 2-chloroadenosine. Adenosine deaminase (5 U/ml) pretreatment of the brain cortices did not diminish the cerebrocortical vascular volume, which increased with arterial hypoxia, topical cyanide poisoning, and direct electrical stimulation. However, it slightly decreased the vasodilative effect of epileptic seizures. On the basis of these results, it seems very unlikely that adenosine is a critical factor in the control of cerebrovascular tone during arterial hypoxia and brain activation.

Adenosine Deaminase↗