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A G Kovách

Publications and source records attributed to A G Kovách.

At least 19 recordsLinked to original sources
PubMed1999

Prevention of the hemorrhagic hypotension-induced hepatic arterial vasoconstriction by L-arginine and naloxone.

The possible involvement of the L-arginine-nitric oxide pathway and endogenous opioid mechanisms in the hemorrhagic hypotension- (HH) induced changes of hepatic arterial blood flow and vascular resistance was studied in cats. During HH hepatic arterial blood flow was significantly higher both in L-arginine- and naloxone-treated animals than in controls. Furthermore, HH induced a significant increase of the hepatic vascular resistance in the control group, which was prevented by L-arginine or naloxone treatment. Because inhibition of the nitric oxide synthesis by N(G)-nitro-L-arginine in normotensive cats induced a similar increase of the hepatic vascular resistance to that observed during HH in the control group, our results indicate that impairment of the endothelial function may be responsible for the hemorrhage-induced L-arginine- and naloxone-reversible hepatic arterial vasoconstriction. This hypothesis is consistent with our previous observations demonstrating the development of endothelial dysfunction in the feline hepatic artery during HH.

Animals↗
PubMed1998

Effect of L-arginine on adrenal and renal blood flows during hemorrhage in cats.

Our earlier studies have shown development of endothelial dysfunction in the feline renal artery during hemorrhagic hypotension. Because L-arginine (L-Arg), the precursor of nitric oxide (NO), reportedly improves endothelial function in several pathophysiological states including hypotension, we investigated its possible beneficial effect on the adrenal and renal circulations during hemorrhagic hypotension in anesthetized, ventilated cats. Hypotension (mean arterial pressure 50 mm Hg) significantly increased vascular resistance and decreased blood flow (radiolabeled microspheres) in both adrenal and renal cortices. L-Arg (30 mg/kg bolus, 10 mg/kg/min infusion, i.v.) had no significant hemodynamic effects in normotension but prevented the increase of the vascular resistance and improved blood flow in the adrenal cortex during hypotension. In the kidney, L-Arg also prevented hemorrhage-induced vasoconstriction, although its effect on blood flow did not reach significance. The NO synthase inhibitor N(G)-nitro-L-arginine (30 mg/kg bolus, 1 mg/kg/min infusion, i.v.) increased adrenal and renal vascular resistances to a similar extent as that observed during hypotension. It thus seems that an L-Arg-reversible dysfunction of the endothelial NO-synthesizing pathway contributes to hemorrhage-induced adrenal and renal vasoconstriction.

Adrenal Glands↗
PubMed1996

The effect of a nitric oxide donor and an inhibitor of nitric oxide synthase on blood flow and vascular resistance in feline submandibular, parotid and pancreatic glands.

The aim was to examine whether (1) blood flow and vascular resistance are altered in response to exogenous nitric oxide and (2) whether endogenous synthesis of nitric oxide participates in the haemodynamic regulation of the submandibular, parotid and pancreatic glands. Experiments were performed on anaesthetized, artificially ventilated cats. Mean arterial blood pressure, heart rate, blood gases, cardiac output and tissue blood flow were determined before and 15 min after intravenous administration of either the nitric oxide donor SIN-1 (3-morpholinosydnonimine, 1 mg/kg, n = 10) or the competitive nitric oxide synthase inhibitor NOLA (NG-nitro-L-arginine, 30 mg/kg, n = 9) blood flow was measured by a radioactive-labelled microsphere method. In the SIN-1 group, in spite of a serious decrease in mean arterial blood pressure (p < 0.001), the blood flow in the glands remained unchanged. The vascular resistance decreased after SIN-1 in the submandibular and pancreatic glands (p < 0.001 and p < 0.05, respectively), and was slightly reduced in the parotid. The NOLA increased mean arterial blood pressure (p < 0.01) and reduced the blood flow in the submandibular and pancreatic glands (p < 0.01 and p < 0.001, respectively), but the decrease in the parotid was not significant. Vascular resistance increased after NOLA in all three glands (p < 0.05, p < 0.001 and p < 0.05). These findings suggest that basal nitric oxide production in these exocrine glands is sufficient to modulate vascular resistance. Moreover, the release of endogenous NO from the nerves and/or endothelium is probably involved in the regulation of vascular tone. The nitric oxide-dependent component of blood-flow regulation, however, seems to be less pronounced in the parotid gland.

Animals↗
PubMed1996

Regional heterogeneity and differential vulnerability of cerebral and spinal vascular CO2-responsiveness during graded haemorrhagic hypotension.

Regional inhomogeneity of cerebrovascular CO2-sensitivity as well as its changes at three different levels of standardized haemorrhagic hypotension were studied in ten distinct brain and spinal cord regions of anesthetized, ventilated cats. Regional cerebral blood flow was measured with radiolabelled microspheres in hypocapnic, normocapnic, and hypercapnic conditions, and CO2-responsiveness was determined from the equation of the slopes of the best fit regression lines to the obtained flow values. It was concluded that in normotensive, normoxic cats response of the cerebral and spinal vessels to PaCO2 alterations can be assigned to four major categories. The CO2-responsiveness of a brain region is not solely determined by the rate of its basal steady state blood flow: CO2-reactivity of the hypothalamus was significantly different from that of any other investigated regions with almost identical steady state flow values. Vulnerability of the cerebrovascular CO2-sensitivity during hypotension was different from region to region, with the vessels of the pons-medulla oblongata region being the most sensitive to haemorrhage. Reduced regional cerebral and spinal CO2-responsiveness during haemorrhage is not a consequence of a reduced L-arginine supply for nitric oxide generation since administration of an excess amount of the precursor L-arginine failed to restore the haemorrhage-induced reduction of regional CO2-sensitivity at the 60 mm Hg mean arterial pressure level.

Animals↗
PubMed1995

Evidence for the role of nitric oxide in the circulation of the dental pulp.

Many authors have studied the hemodynamics of the dental pulp; however, there are scarcely any data regarding the involvement of the L-arginine/nitric oxide pathway in the regulatory mechanism. Thus, we have examined the physiological effects of (1) NG-nitro-L-arginine as an inhibitor of nitric oxide synthesis and (2) the nitric oxide donor 3-morpholinosydnonimine on blood flow and vascular resistance in the canines of anesthetized cats to study the potential involvement of nitric oxide in the regulation of dental vascular homeostasis. Mean arterial blood pressure, heart rate, blood gases, pH, cardiac output, and tissue blood flow were determined prior to and 15 min after i.v. administration of either NG-nitro-L-arginine (30 mg/kg, n = 9) or 3-morpholinosydnonimine (1 mg/kg, n = 7). Blood flow was measured by radioactive-labeled microspheres. There were no significant differences in baseline parameters between the two groups of cats. The dental pulp blood flow decreased to 53 +/- 13% (p < 0.01) of the control level after NG-nitro-L-arginine administration, while it decreased only slightly (to 82 +/- 12%) after 3-morpholinosydnonimine administration. The dental pulp's vascular resistance increased to 367 +/- 69% (p < 0.01) of the control level after NG-nitro-L-arginine, while it decreased to 73 +/- 10% (p < 0.05) of control after 3-morpholinosydnonimine. We found that the L-arginine/nitric oxide pathway plays an important role in the regulation of pulpal blood circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of superoxide dismutase on hemorrhagic hypotension and retransfusion-evoked middle cerebral artery endothelial dysfunction.

UNLABELLED: Middle cerebral artery rings (MCA) were prepared from control and hemorrhagic hypotension and retransfusion-subjected (HHR) cats, with or without superoxide dismutase (SOD) treatment. Two-mm-long MCA segments were suspended in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurements. HHR was produced by bleeding to 90, 70, and 50 mmHg MAP and maintained for 15 min at each level, followed by retransfusion. HHR resulted in a marked attenuation of the acetylcholine- and ATP-induced endothelium-dependent relaxations of the MCA in vitro. Relaxations induced by the nitric oxide (NO) donor SIN-1 remained unaltered. In vitro treatment of the vessels with SOD (150 U/ml), facilitated the acetylcholine-induced relaxations both in the control arteries and in the vessels after HHR. In the vessel rings from cats that received in vivo SOD (10 mg/kg initial bolus, followed by 0.1-mg/kg/min infusion) during HHR, cholinergic relaxations were more pronounced than in the HHR untreated cats. The ATP-induced relaxations, however, remained attenuated after SOD treatment, except for the highest dose (10(-5) M) that was applied. CONCLUSION: Superoxide release attenuates the endothelium-dependent relaxation by acetylcholine both in control arteries and after HHR in vitro. The protective effect of in vivo SOD treatment on cerebrovascular endothelium-dependent reactivity in cats suggests that superoxide free radicals contribute to the development of the endothelium dysfunction in MCA rings after HHR.

Acetylcholine↗
PubMed1994

ATP and pH predictors of histologic damage following global cerebral ischemia in the rat.

In vivo changes of high energy phosphates and pH were determined with 31P NMR spectroscopy in rats subjected to symmetric or asymmetric partial global ischemia with reperfusion. Tissue damage was assessed by histology. ATP depletion, following PCr depletion, developed shortly after the onset of ischemia. In prolonged ischemia reperfusion was not followed with full recovery. APT depletion of more than 20% during reperfusion was associated with histologic damage; marked necrosis was associated with 50% reduction. Although during ischemia, severe persisting intracellular acidosis developed sometimes, and it was also associated with tissue damage, it did not appear to elicit tissue damage independently of the ATP depletion. Splitting of the Pi peak was useful in predicting heterogeneous distribution of the necrosis, thus it can reflect a heterogeneous distribution of the intracellular pH.

Adenosine Triphosphate↗
PubMed1992

Role of platelet-activating factor in the development of endothelial dysfunction in hemorrhagic hypotension and retransfusion.

Platelet-activating factor (PAF), an important mediator of ischemic and shock states, has been shown to prime direct and neutrophil-mediated endothelial cell injury. In the present study we investigated therefore whether PAF is involved in the development of dysfunction of the cerebrovascular endothelium in hemorrhagic hypotension and retransfusion in cats. In vitro responses of middle cerebral arteries prepared from control animals and from animals subjected to hemorrhagic hypotension with or without specific PAF antagonist WEB 2086 treatment (1 mg/kg initial bolus followed by a 0.05 mg/kg/min infusion) were studied by measuring isometric force in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2). Bleeding was performed in a stepwise fashion by bringing the mean arterial blood pressure to 90, 70 and 50 mmHg and maintained for 20 min at each level followed by a 20-min retransfusion. Hemorrhagic hypotension and retransfusion caused a marked attenuation of the acetylcholine- and ATP-induced endothelium-dependent relaxations of the middle cerebral artery whereas the dilations induced by the nitric oxide donor and direct vasorelaxant SIN-1, remained unaltered. In the vessels, prepared from animals which received WEB 2086 treatment during hemorrhage and retransfusion there were more pronounced cholinergic (but not purinergic) relaxations than in the untreated animals subjected to hemorrhage. SIN-1 induced relaxations remained unaltered after WEB 2086 treatment. Our results suggest that platelet-activating factor is in part involved in the pathophysiological processes leading to the development of the endothelial dysfunction in the present model of hemorrhagic hypotension and retransfusion.

Animals↗
PubMed1992

Role of endothelium in the response of the vein wall to magnesium withdrawal.

Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In noradrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5 x 10(-6) M), and in vessels without endothelium, lowering the magnesium concentration caused a dose-dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of NG-nitro-L-arginine and L-arginine on regional cerebral blood flow in the cat.

1. We studied the effects of NG-nitro-L-arginine (NOLA), a potent inhibitor of the L-arginine-nitric oxide pathway, and L-arginine, the precursor of nitric oxide, on regional cerebral blood flow, electrocortical activity and ex vivo cerebrovascular reactivity in the cat. Flow was measured via radiolabelled microspheres, and vascular responses were studied by measuring isometric tension of isolated middle cerebral arterial rings. 2. NOLA (30 mg kg-1 bolus followed by 1 mg kg-1 min-1 infusion) caused an approximately 40 mmHg elevation in the mean arterial blood pressure, a regionally heterogenous increase of the regional cerebrovascular resistance and a decrease in the regional cerebral blood flow 15 and 40 min after the start of its administration. In contrast L-arginine (30 mg kg-1 bolus followed by 10 mg kg-1 min-1 infusion) did not alter blood pressure, cerebrovascular resistance nor regional cerebral blood flow 15 min after the start of its administration. The NOLA-induced changes in tissue flow were the most pronounced in the cerebellum, pituitary and medulla oblongata, whereas there was no decrease in the flow of the cortex and white matter. 3. NOLA caused characteristic changes in total fronto-occipital EEG power and in power spectra which were unlikely to have been due to cerebral ischaemia. In addition, the ex vivo reactivity of the middle cerebral arteries showed signs of impaired endothelial nitric oxide synthesis: there were enhanced noradrenaline-induced contractions and N-ethoxycarbonyl-3-morpholino-sydnonimine (SIN-1)-induced relaxations and markedly attenuated acetylcholine- and ATP-induced relaxations after NOLA treatment. 4. The present data indicate that resting cerebral blood flow and cerebrovascular resistance are regulated by nitric oxide derived from L-arginine in a regionally heterogenous way and that exogenous L-arginine availability is not a limiting factor in this nitric oxide generation. Possibly, both the vascular endothelium and the neurons contribute to this basal nitric oxide release.

Animals↗
PubMed1992

Role of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion.

We studied the involvement of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion. Feline middle cerebral arteries were prepared from control animals killed under anesthesia and from anesthetised animals subjected to hemorrhagic hypotension (stepwise bleeding to 90, 70, and 50 mmHg, maintained for 20 min at each level) followed by retransfusion (20 min). Two-mm-long vessel segments were suspended in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurements. Contractions to noradrenaline (norepinephrine), relaxations to acetylcholine, ATP, adenosine, and SIN-1, a nitric oxide donor compound, were compared in the vessels of the control and hemorrhage-subjected animals. Contractile responses to noradrenaline were significantly enhanced after hemorrhage, whereas relaxations to acetylcholine, ATP, and adenosine were significantly reduced. Relaxations to SIN-1, however, remained unchanged. L-Arginine did not cause relaxations in control vessels but relaxed the arteries after hemorrhage and retransfusion. To clarify the involvement of the L-arginine-nitric oxide pathway in these alterations, we studied the effect of exogenous application of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF) and NG-nitro-L-arginine (NOLA), a competitive antagonist of the EDRF-producing enzyme on the vascular responses in vitro. Similar to the effect of hypotension and retransfusion, NOLA enhanced the noradrenaline-induced contractions and inhibited the acetylcholine-induced and purinoceptor-mediated relaxations in the control arteries. In the control vessels in vitro, L-arginine treatment did not modify any contractile or relaxant response. At the same time, in vitro L-arginine treatment inhibited the hemorrhagic hypotension-induced enhancement of the contractions to noradrenaline and restored the diminished relaxations to acetylcholine (but not to ATP or adenosine). In the vessels after hemorrhage, NOLA neither further enhanced the already markedly enhanced noradrenaline-induced contractions nor further inhibited the relaxations caused by ATP and adenosine. In the case of acetylcholine, however, NOLA caused a further inhibition of the relaxations. The effect of in vivo L-Arg infusion (30 mg/kg initial bolus and 10 mg/kg/min infusion) during hemorrhagic hypotension and retransfusion on the in vitro vascular reactivity was similar to that of the in vitro L-arginine treatment. The present study demonstrates that even short-lasting hemorrhagic hypotension combined with retransfusion markedly inhibits nitric oxide-mediated, agonist-induced endothelium-dependent cerebrovascular responses. In vivo or in vitro L-arginine treatment is able to restore normal responses to some agents.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1992

Hemorrhagic hypotension impairs endothelium-dependent relaxations in the renal artery of the cat.

The effect of hemorrhagic shock on the vasodilatory responses of the feline renal artery was studied in vitro. In sodium pentobarbital anaesthetized cats, a steady level of hypotension (50 mm Hg) was reached by bleeding into a reservoir and maintained at this level by further bleeding or autotransfusion for 2 hr (shock). One to 3 mm long rings of the arteries (from control and shocked animals) were suspended for isometric tension recording in organ chambers filled with modified Krebs-Henseleit solution, aerated with 95% O2-5% CO2 at 37 degrees C. The experiments were performed in the presence of indomethacin and propranolol to inhibit cyclooxygenase activity and beta-adrenoceptors, respectively. Endothelium-dependent relaxations induced by acetylcholine and ATP were significantly inhibited in the vessels after hemorrhagic shock. In contrast, endothelium-independent vasodilation induced by adenosine remained unchanged after this shock state. The present results suggest a marked and selective impairment of the endothelial function of the renal artery of hemorrhagic shock. This alteration of the renovascular reactivity might play an important role in the development of vasoconstriction in the renal vasculature during and after this hemorrhagic shock state.

Acetylcholine↗
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

Importance of basal nitric oxide synthesis in regulation of myocardial blood flow.

STUDY OBJECTIVE: The aim was to investigate whether basal coronary vascular tone and myocardial perfusion depend upon endothelial nitric oxide (NO) synthesis. DESIGN: Myocardial blood flow and vascular resistance of the left and right ventricles were studied before and after intravenous infusions of either NG-nitro-L-arginine (L-NA), a specific inhibitor of NO synthase, or L-arginine, the precursor of NO synthesis. Radiolabelled microspheres were used to study myocardial blood flow in small tissue sections. EXPERIMENTAL MATERIAL: 14 anaesthetised male cats, weight 2.1-3.5 kg, were used. MEASUREMENTS AND MAIN RESULTS: Measurements were made before and 15 and 40 min after L-NA treatment (30 mg.kg-1 bolus followed by 1 mg.kg-1.min-1 infusion; n = 8), and before and 15 min after L-arginine treatment (30 mg.kg-1 bolus followed by 10 mg.kg-1.min-1 infusion; n = 6). L-NA significantly reduced coronary blood flow to the left and right ventricle, by 30(SEM 9) and 48(6)% respectively, after 15 min, but only to the right ventricle, by 45(8)%, after 40 min. Mean arterial pressure and myocardial vascular resistance were raised during the L-NA infusion. In contrast, L-arginine did not elicit any change in the variables studied. CONCLUSIONS: The conductance of the coronary vascular bed and the resting myocardial blood flow is regulated by L-arginine derived nitric oxide, and exogenous L-arginine availability is not a limiting factor in this NO generation.

Animals↗
PubMed1991

Effect of local pH on interstitial fluid pressure.

It has been suggested that electrostatic interactions between the electric charges on the interstitial gel matrix play a significant role in determining tissue elasticity and interstitial fluid pressure (IFP). The relationship between the net charge and IFP, however, has not been adequately established. Our purpose was to explore the net electric charge-IFP relationship, and in vivo experiments were performed to test its validity. IFP was measured in the subcutaneous tissue of anesthetized rats with the chronically implanted capsule method, and the acid-base status in blood and interstitial fluid was monitored. The net charge, which can be varied by pH, was altered by electrolysis procedure. H+ and OH- generated inside the capsule caused transient and dose-dependent IFP responses. The curve, describing the relationship between capsular pressure changes and amount of generated H+ and OH-, has a maximum at zero net charge, and the excess electric charge, either positive or negative, results in a significant decrease in capsular pressure in accordance with the hypothesis. The time course, as well as the dose dependency, of IFP suggests that the subcutaneous tissue gel in control condition has slightly positive net charge.

Animals↗
PubMed1991

Effect of hemorrhagic hypotension on cerebrovascular reactivity and ultrastructure in the cat.

BACKGROUND AND PURPOSE: The goal of this study was to determine the alterations in contractile and dilatory responses and ultrastructure of the feline middle cerebral artery after hemorrhagic hypotension. METHODS: In the sodium pentobarbital anesthetized cats, a steady 50 mm Hg level of hypotension was reached by bleeding into a reservoir and maintained at this level by further bleeding or autotransfusion for 2 hours. Rings of the arteries, from control animals and from animals after hypotension, were suspended for isometric tension recording in organ chambers filled with modified Krebs-Henseleit solution, aerated with 95% O2-5% CO2 at 37 degrees C, and their reactions to contractile and relaxant agents were tested. Vascular ultrastructure was studied by electron microscope. RESULTS: Endothelium-dependent relaxations induced by 10(-8) M acetylcholine were enhanced, whereas there was a marked inhibition of the relaxation at 10(-6) M. Relaxations induced by adenosine triphosphate and adenosine showed an impairment. Contractions induced by norepinephrine and prostaglandin F2 alpha remained unchanged, whereas 5-hydroxytryptamine caused a more pronounced contraction after hypotension. No alterations in the morphology of endothelium or smooth muscle were found after hemorrhage. There was, however, a marked decrease in the number of transmitter vesicles in the perivascular nerve terminals. CONCLUSIONS: The present results show marked alterations in cerebrovascular reactivity and ultrastructure of the adventitia after hypotension. These alterations might play an important role in the development of cerebral vasoconstriction during and after this hemorrhagic state.

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↗