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Biomedical subjects

E Okabe

Publications and source records attributed to E Okabe.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of enflurane on contractile reactivity in isolated canine mesenteric arteries and veins.

The effects of enflurane on responses of isolated canine mesenteric arteries and veins to transmural nerve stimulation and to exogenously administered norepinephrine (a mixed alpha 1- and alpha 2-adrenoceptor agonist), phenylephrine (a selective alpha 1-adrenoceptor agonist), and tyramine were studied. The contractile responses of the arteries and the veins to transmural nerve stimulation and to norepinephrine were attenuated by exposure to enflurane; the responses to phenylephrine were decreased more than those to norepinephrine. When compared with the effect of enflurane on transmural nerve stimulation-induced responses, exposure to enflurane resulted in slight attenuation of the contractile responses caused by tyramine, suggesting that enflurane may inhibit the responses to tyramine by interfering with an interaction between released norepinephrine and postjunctional alpha 1-adrenoceptors rather than with tyramine-induced norepinephrine release. The data are also consistent with the view that enflurane acts on sympathetic nerve endings to inhibit release of norepinephrine associated with electrical stimulation-induced nerve membrane depolarization.

Animals↗
PubMed1989

Direct pharmacological action of vasoactive substances on pulpal blood flow: an analysis and critique.

An adequate blood supply to the dental pulp is essential to the health of the tooth; therefore, there have been a number of efforts to study pulpal blood flow and the factors which influence it. However, blood flow to the dental pulp is relatively inaccessible and apparently quite low. Consequently, it is difficult to obtain accurate flow measurements, partly owing to methodological difficulties with the small size of the tissue and its enclosure within rigid walls. In this study, the effects of locally applied vasoactive substances and their specific antagonists on pulpal blood flow have been examined by laser Doppler flowmetry. It is the purpose of this article to examine, in-depth, the involvement of endogenous vasoactive substances in the regulatory mechanism of blood flow within the dental pulp and expand our knowledge of pulpal microcirculatory hemodynamics.

Animals↗
PubMed1989

Possible mechanism responsible for mechanical dysfunction of ischemic myocardium: a role of oxygen free radicals.

It has been proposed that a major target organelles damaged by the ischemic process, probably by the oxygen free radicals generated, is the portion of the excitation-contraction coupling system that regulates Ca2+ delivery (the sarcoplasmic reticulum and sarcolemma) to the contractile proteins. We tested this hypothesis by studying the effect of in vitro generation of oxygen free radicals from xanthine-xanthine oxidase system or dihydroxyfumarate (DHF)/Fe3+-ADP system on Ca2+ flux behavior of canine cardiac sarcoplasmic reticulum (SR); sarcolemmal (Na+, K+)-ATPase and Na+-Ca2+ exchange activities; and myofibrillar (Ca2+, Mg2+)-ATPase activity. Generation of oxygen free radicals by xanthine oxidase acting on xanthine as a substrate increased the passive Ca2+ efflux and decreased intravesicular Ca2+ with no effect on active Ca2+ influx (Ca2+-ATPase) of SR vesicles. Similar exposure of sarcolemmal vesicles to xanthine plus xanthine oxidase stimulated Na+-Ca2+ exchange activity. When sarcolemmal vesicles were incubated with DHF plus Fe3+-ADP, (Na+, K+)-ATPase activity was decreased. It is postulated that the SR Ca2+ efflux pathways but not catalytic activity of the Ca2+ pump and sarcolemmal (Na+, K+)-ATPase involving Na+-Ca2+ exchange activity are altered by oxygen free radicals, and such changes may partly account for the occurrence of intracellular Ca2+ overload during the course of myocardial ischemia. Interestingly, oxygen free radicals from xanthine-xanthine oxidase system had no effect on myofibrillar pCa-ATPase curve. From this set of observations we would hypothesize that the SR and sarcolemma may be the principal target organelles of oxygen free radicals attack in the ischemic injury and not the contractile proteins per se.

Animals↗
PubMed1989

[A study on the mechanism of phleboid olfactory function].

Phleboid olfactory test has wide clinical application for olfactory disturbance. Many unclarified aspects still remain concerning the mechanism of smell after an intravenous infusion of Alinamin. It is believed that when Alinamin is infused intravenously and byproducts are discharged from the blood into the alveoli, odorous substances reach the nasal cavity through exhalation. In order to clarify the mechanism of smell in more detail, we conducted the following experiments: 1) Cases of laryngectomy were examined to determine if intravenous infusion of Alinamin affected the olfactory organ. 2) Saliva specimens in healthy subjects were collected before and after intravenous infusion of Alinamin and examined for the presence of a secreted odorous substance using a functional test. 3) Healthy subjects who were inhibited in their sense of smell were examined for the presence of garlic odor after intravenous infusion of Alinamin. The results were as follows: 1) 80% of subjects of laryngectomy without cotton in the nares and 20% of subjects of laryngectomy with cotton in the nares perceived the garlic odor. 2) Garlic odorous substance was not recognized in saliva specimens collected before and after intravenous infusion of Alinamin. 3) The healthy subjects inhibited in their sense of smell and intravenously infused with Alinamin perceived the odor at the same time as exhalation. The above results indicated that the mechanism of smell after intravenous infusion of Alinamin occurred via exhalation, but not through the other routes.

Adult↗
PubMed1989

Calmodulin and free oxygen radicals interaction with steady-state calcium accumulation and passive calcium permeability of cardiac sarcoplasmic reticulum.

The generation of free oxygen radicals from the xanthine-xanthine oxidase system produced a decrease in the steady-state calcium load of canine cardiac sarcoplasmic reticulum (SR) vesicles and an increase in the SR passive calcium permeability. This effect of free oxygen radicals was completely inhibited by superoxide dismutase, a scavenger of superoxide anion radical (.O2-). Treatment of intact SR with a specific calmodulin antagonist, compound 48/80 or W-7, lead to the enhancement of the free oxygen radical-mediated reduction of steady-state calcium accumulation with little effect on passive calcium permeability and Ca,Mg-adenosine triphosphatase activity. The effects of free oxygen radicals and the calmodulin antagonists on steady-state calcium accumulation, but not on passive calcium permeability, were only observed in the presence of the endogenous calmodulin of SR vesicles. These results indicate that stimulation by .O2- and/or a closely related species of free oxygen radical of the passive calcium leak pathway is not calmodulin-dependent and is not a potent way of changing the steady-state calcium accumulation. Hence, we propose that calmodulin-dependent component of calcium fluxes in cardiac SR vesicles is modified directly by free oxygen radicals, and that free oxygen radicals can reduce steady-state calcium accumulation due to increased calcium release through a calcium efflux pathway which is inhibited by calmodulin, but not due to reduced catalytic activity of the pump.

Animals↗
PubMed1988

Oxygen radical-mediated lipid peroxidation and inhibition of Ca2+-ATPase activity of cardiac sarcoplasmic reticulum.

Oxygen radicals have been implicated as important mediators of myocardial ischemic and reperfusion injury. A major product of oxygen radical formation is the highly reactive hydroxyl radical via a biological Fenton reaction. The sarcoplasmic reticulum is one of the major target organelles injured by this process. Using a oxygen radical generating system consisting of dihydroxyfumarate and Fe3+-ADP, we studied lipid peroxidation and Ca2+-ATPase of cardiac sarcoplasmic reticulum. Incubation of sarcoplasmic reticulum with dihydroxyfumarate plus Fe3+-ADP significantly inhibited enzyme activity. Addition of superoxide dismutase, superoxide dismutase plus catalase (15 micrograms/ml) or iron chelator, deferoxamine (1.25-1000 microM) protected Ca2+-ATPase activity. Time course studies showed that this system inhibited enzyme activity in 7.5 to 10 min. Similar exposure of sarcoplasmic reticulum to dihydroxyfumarate plus Fe3+-ADP stimulated malondialdehyde formation. This effect was inhibited by superoxide dismutase, catalase, singlet oxygen, and hydroxyl radical scavengers. EPR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide verified production of the hydroxyl radical. The combination of dihydroxyfumarate and Fe3+-ADP resulted in a spectrum of hydroxyl radical spin trap adduct, which was abolished by ethanol, catalase, mannitol, and superoxide dismutase. The results demonstrate the role of oxygen radicals in causing inactivation of Ca2+-ATPase and inhibition of lipid peroxidation of the sarcoplasmic reticulum which could possibly be one of the important mechanisms of oxygen radical-mediated myocardial injury.

Adenosine Diphosphate↗
PubMed1988

The effect of oxygen free radicals on calcium permeability and calcium loading at steady state in cardiac sarcoplasmic reticulum.

It has been proposed that oxygen free radical production is an important mediator of the myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the pathway of calcium efflux across sarcoplasmic reticulum (SR) membranes affected by oxygen free radicals. The effect of oxygen free radicals on the steady state calcium load, calcium permeability, and Ca,Mg-ATPase activity of isolated canine cardiac SR vesicles was investigated at pH 7.0. In vitro generation of oxygen free radicals by xanthine oxidase (0.09 units/ml), acting on xanthine in doses up to 50 microM as a substrate, increased the permeability of the SR vesicles to calcium, determined by measuring net efflux of calcium after stopping pump-mediated fluxes, and decreased total intravesicular calcium and free intravesicular calcium with no effect on Ca,Mg-ATPase activity. The effect of oxygen free radicals on calcium permeability was calcium gradient-dependent. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD, 56 units/ml), but not denatured SOD, significantly inhibited the effect of xanthine-xanthine oxidase reaction. The calcium permeability of the SR membrane decreased with decreasing calcium load. In addition, inasmuch as extravesicular calcium exerts only a slight effect on calcium permeability, the decrease in the permeability with calcium load is specifically related to the calcium load. Oxygen free radical-induced increase in calcium permeability was unaffected by Mg concentration between 2.1 and 21 mM. In summary, our data reveal that .O2- can produce a diminished level of accumulated calcium, which is reflected by the decreased calcium load and an increase in passive calcium permeability, and that the decreased calcium accumulation in the presence of the xanthine-xanthine oxidase system may not be mainly due to an inhibited calcium pump but due to an increased calcium permeability. Our results also suggest that increased SR membrane passive calcium permeability induced by oxygen free radicals is not carrier mediated. It is postulated that, with the oxygen free radical-mediated progressive increase in calcium permeability, free cytosolic calcium concentrations would increase in ischemic myocardium.

Animals↗
PubMed1987

Calmodulin participation in oxygen radical-induced cardiac sarcoplasmic reticulum calcium uptake reduction.

The effect of scavengers of oxygen radicals on canine cardiac sarcoplasmic reticulum (SR) Ca2+ uptake velocity was investigated at pH 6.4, the intracellular pH of the ischemic myocardium. With the generation of oxygen radicals from a xanthine-xanthine oxidase reaction, there was a significant depression of SR Ca2+ uptake velocity. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD), a scavenger of .O2-, or denatured SOD had no effect on the depression of Ca2+ uptake velocity induced by the xanthine-xanthine oxidase reaction. However, catalase, which can impair hydroxyl radical (.OH) formation by destroying the precursor H2O2, significantly inhibited the effect of the xanthine-xanthine oxidase reaction. This effect of catalase was enhanced by SOD, but not by denatured SOD. Dimethyl sulfoxide (Me2SO), a known .OH scavenger, completely inhibited the effect of the xanthine-xanthine oxidase reaction. The observed effect of oxygen radicals and radical scavengers was not seen in the calmodulin-depleted SR vesicles. Addition of exogenous calmodulin, however, reproduced the effect of oxygen radicals and the scavengers. The effect of oxygen radicals was enhanced by the calmodulin antagonists (compounds 48/80 and W-7) at concentrations which showed no effect alone on Ca2+ uptake velocity. Taken together, these findings strongly suggest that .OH, but not .O2-, is involved in a mechanism that may cause SR dysfunction, and that the effect of oxygen radicals is calmodulin dependent.

Animals↗
PubMed1986

Effect of potassium gluconate on potassium transport of rat erythrocytes.

Effect of potassium gluconate (K-GL) on K+ uptake of rat erythrocytes was investigated. K-GL produced a significant increase in active K+ transport of Na+-rich erythrocytes, while Na+,K+-ATPase activity of hemoglobin-free ghosts without a glycolytic system was unaffected. When the experiment was carried out in intact erythrocytes, K-GL increased the lactate production and ATP content, and it promoted the methemoglobin reduction rate. In Na+-rich erythrocytes, the glycolysis inhibitors which produced a marked reduction in lactate content abolished the K-GL-induced increase in K+ and ATP content without affecting the KCl-induced increase. These results suggest that K-GL enhances K+ transport of erythrocytes through acceleration of glycolytic process.

Adenosine Triphosphatases↗
PubMed1985

Inhibition by free radical scavengers and by cyclooxygenase inhibitors of the effect of acidosis on calcium transport by masseter muscle sarcoplasmic reticulum.

In vitro, arachidonic acid depressed calcium transport by sarcoplasmic reticulum (SR) in the homogenate of canine masseter muscle. This effect was inhibited by superoxide dismutase (SOD), a scavenger of the superoxide anion radial ( . O-2), at pH 7.0, and by SOD plus d-mannitol, a scavenger of hydroxyl free radical ( . OH), at pH 5.5. Indomethacin and 2-aminomethyl-4-tert-butyl-6-propionyl phenol (ONO-3144), a compound known to accelerate the conversion of prostaglandin G2 (PGG2) to PGH2 and scavenge free radicals, inhibited the effect of arachidonic acid at both pH 7.0 and pH 5.5. PGG2, but not PGH2, duplicated the effect of arachidonic acid. The effect of PGG2 on SR function was similar to that of exogenous free radicals generated from the xanthine-xanthine oxidase system. Incubation at pH 5.5, in the absence of an exogenous free-radical generating system, depressed SR calcium transport in the homogenate and in isolated SR. This effect in the homogenate was inhibited by indomethacin or by ONO-3144. At 10-min incubation at pH 5.5, SOD partially and temporarily reversed the depressant effect of acidosis. The addition of SOD plus d-mannitol completely reversed the system. d-Mannitol alone was ineffective. Arachidonic acid was able to mimic these effects of acidosis, except that arachidonic acid further depressed isolated SR calcium transport. These results demonstrate that acidosis can depress SR calcium transport in the homogenate of masseter muscle by an oxygen-free radical mechanism by the generation of . O-2 and . OH. Our results also demonstrate that significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism at an acidotic pH in the cellular environment outside of the SR of the muscle cell, and seems to be responsible for the generation of the . OH derived from . O-2.

Acidosis↗
PubMed1985

Characterization of the effect of pH on the excitation-contraction coupling system of canine masseter muscle.

The effect of pH on the excitation-contraction coupling system of canine masseter muscle was studied by evaluating the functional integrity of the sarcoplasmic reticulum (SR) and myofibrils. Increasing proton concentration (pH 7.0-5.8) significantly reduced oxalate supported SR calcium uptake velocity, while Ca2+-stimulated, Mg2+-dependent ATPase activity was unaffected by pH. The efficiency ratio of calcium transport, or the coupling ratio (mumoles Ca2+ transported/mumoles ATP hydrolyzed), decreased from 1.094 +/- 0.042 at pH 7.0 to 0.946 +/- 0.036 at pH 6.0 (P less than 0.05) and to 0.780 +/- 0.024 at pH 5.8 (P less than 0.01). Myofibrillar pCa (-log [free Ca2+] )-ATPase activity was unaffected between pH 7.0 and pH 6.5. At pH 6.0, increasing Ca2+ concentration inhibited myofibrillar ATPase activity, and this inhibitory phenomenon was accentuated at pH 5.8. Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km at low pH. It is concluded that acidosis significantly uncouples calcium transport from ATP hydrolysis in the SR of masseter muscle and significantly alters myofibrillar ATPase activity. It is hypothesized that these defects may explain an observed depression in skeletal muscle cell function during ischemia.

Adenosine Triphosphatases↗