PubMed Health⌕ Search

Biomedical subjects

E Okabe

Publications and source records attributed to E Okabe.

70 records · Page 4Linked to original sources
PubMed1984

Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates.

Generation of oxygen free radicals by xanthine acting on xanthine oxidase as a substrate significantly depressed calcium transport by sarcoplasmic reticulum in canine whole heart homogenates at 37 degrees C. At pH 7.0, this effect was completely inhibited by the addition of superoxide dismutase (SOD), a scavenger of the superoxide anion radical. At pH 6.4, SOD (5 to 20 micrograms X ml-1) was ineffective but catalase (20 micrograms X ml-1) was able to inhibit the effects of the xanthine-xanthine oxidase system. SOD + catalase (20 micrograms X ml-1) and SOD + mannitol, a scavenger of the hydroxyl free radical, inhibited the effects of the xanthine-xanthine oxidase system at pH 6.4. Preincubation at pH 6.4, in the absence of an exogenous free radical generating system, depressed calcium transport. This depression was more severe the longer the duration of incubation. However, return of the pH to 7.0 after preincubation at pH 6.4 partially restored calcium uptake velocity. The degree of reversibility was decreased the longer the period of incubation at pH 6.4. SOD reversed the effects of incubation at pH 6.4 for 5 min, but not those for incubations of 10 and 15 min. Mannitol alone was ineffective. The combinations of SOD and mannitol significantly reversed the effects of pH 6.4 up to 15 min. These results demonstrate that both exogenously generated and endogenously generated free oxygen radicals are capable of depressing calcium transport by cardiac sarcoplasmic reticulum in the whole heart homogenate in the presence of endogenous scavenging systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1983

Characterization of free radical-mediated damage of canine cardiac sarcoplasmic reticulum.

In vitro generation of free radicals by xanthine oxidase acting on xanthine as substrate depressed steady-state calcium uptake by canine cardiac sarcoplasmic reticulum vesicles. The effect of free radicals on the calcium-dependent ATPase activity of the SR vesicles was pH dependent. At pH 7.0, ATPase activity was decreased, but at pH 6.4 it was unchanged. Exposure to free radicals increased the passive permeability of the vesicles to calcium. This increase was inhibited by superoxide dismutase (SOD) at pH 7.0, and SOD plus mannitol at pH 6.4. The increased permeability per se was insufficient to explain the effects of free radicals on ATPase activity, since the calcium ionophore A23187 was unable to mimick these effects. Direct measurement of the number and turnover of the pump units indicated that the number of units was unchanged but turnover was decreased by free radicals at pH 7.0. The overall data suggest at least two mechanisms of free radical damage, one associated with an increase in passive permeability and another associated with an as yet undefined change in some specific steps of the ATPase reaction.

Animals↗
PubMed1983

Anaphylaxis-induced increase in plasma cyclic AMP dependent on endogenous catecholamines in rats.

Plasma cyclic AMP levels during anaphylactic shock in rats was studied in 7 groups of animals: (1) control rats; (2) rats with adrenomedullectomy; (3) rats treated with propranolol; (4) rats with reserpinization; (5) rats with 6-hydroxydopamine-induced chemical sympathectomy; (6) rats treated with hexamethonium, and (7) rats treated with cocaine (catecholamine uptake inhibitor). All experiments were carried out in ovalbumin-sensitized rats. Plasma cyclic AMP showed a rapid increase during anaphylactic shock in control rats. Adrenomedullectomy abolished the anaphylaxis-induced increase in plasma cyclic AMP, while hexamethonium had no effect. Propranolol caused a dose-dependent abolition of the increase. The treatment of rats with reserpine, 6-hydroxydopamine or cocaine partially inhibited the increase in plasma cyclic AMP. The results show that the adrenal medulla is the major source of catecholamines during anaphylactic shock, and that catecholamines in the adrenergic neuronal terminals may be partly responsible for the anaphylaxis-induced increase in plasma cyclic AMP.

Adrenal Medulla↗
PubMed1983

Free radicals-induced changes in mesenteric microvascular dimensions in the anesthetized cat.

Effect of free radicals on microvascular dimensions was studied in anesthetized cat intestinal mesentery. Generation of free radicals by xanthine oxidase, acting on endogenous substrates (e.g., xanthine, hypoxanthine), produced sustained vasodilation at pH 7.4 or at pH 6.6. These effects were reversed by superoxide dismutase (SOD), a superoxide radical (.O2-) scavenger, at pH 7.4, and by SOD plus hydroxyl radical (.OH) scavenger d-mannitol at pH 6.6. These findings suggest that the sustained vasodilation is caused by .O2- and by .OH derived from .O2- at low pH.

Anesthesia↗
PubMed1982

Free radical damage to sarcoplasmic reticulum of masseter muscle by arachidonic acid and prostaglandin G2.

In vitro generation of free radicals by xanthine oxidase acting on hypoxanthine as a substrate induced a decreased calcium uptake velocity and reduced calcium-dependent ATPase activity of isolated sarcoplasmic reticulum (SR) vesicles from canine masseter muscle at pH 7.0. At pH 5.5 calcium uptake velocity was also reduced but ATPase activity was unaffected. Application of arachidonic acid or prostaglandin G2 induced the depression of both calcium uptake velocity and ATPase activity. The effect of arachidonic acid and prostaglandin G2 on ATPase activity depended on the pH. At pH 7.0, ATPase activity was decreased, but at pH 5.5 it was unchanged. These effects were reversed by superoxide dismutase (SOD) at pH 7.0, and by SOD plus mannitol at pH 5.5. Prostaglandin H2, prostaglandin E2 and 11,14,17-eicosatrienoic acid had no effect on calcium uptake velocity and ATPase activity at both pH 7.0 and pH 5.5. These results suggest that damage to the masseter muscle is caused by a free radical superoxide anion generated as a result of increased prostaglandins synthesis, and by the production of more lethal hydroxyl radical switched from the production of superoxide anion at low pH.

Adenosine Triphosphatases↗
PubMed1981

Effects of perhexiline on myocardial phosphorylase activity, myocardial catecholamine content and heart rate.

A study was conducted on the effects of perhexiline on myocardial phosphorylase activity, myocardial catecholamine content and heart rate. Phosphorylase a activity and heart rate were investigated as an indicator of sympathetic nerve tone in order to clarify the characteristic of perhexiline with regard to the effects on myocardial metabolism in hyperthyroid rats and catecholamine deficient rats. Myocardial catecholamine and phosphorylase a activity were measured by von Euler's method and Cori's method respectively. Conclusion of this study are summarized as follows: 1) Perhexiline reduces the heart rate, and its effect is not always dependent upon the changes in myocardial norepinephrine content. 2) Perhexiline reduces myocardial phosphorylase a activity. It cannot be always said that the reduction is dependent upon the changes in myocardial norepinephrine. 3) Though slightly different from propranolol and dichloroisoproterenol, perhexiline possesses cardiac effects resembling beta-blockers.

Animals↗
PubMed1981

Augmented venous return: a model of left ventricular afterload reduction during the course of endotoxin shock.

Utilizing a canine model of endotoxin shock (E coli, 4 mg/kg, B6:026) the major determinants of cardiac output (preload, afterload, contractility, and heart rate) were simultaneously followed for 5 hr in four study groups: Group I: time-matched controls, Group II: endotoxin shock, Group III: endotoxin shock and femoral-femoral A-V shunt, and Group IV: A-V shunt control. Groups II and III demonstrated an initial, abrupt increase in total peripheral resistance (TPR), coronary vascular resistance (CVR), and pulmonary vascular resistance (PVR), and a decrease in cardiac output (CO), coronary flow (CF) and heart rate (HR) and stroke work (P less than 0.05). Group II then demonstrated a decrease in TPR, CVR, PVR with an increase in CO and CF but systemic arterial pressure did not return to control values. At approximately 3 hr, Group II developed a progressive increase in TPR, CVR, and PVR, and a decrease in CO, CF, and SW. Heart rate did not change. In contrast, at 3 hr Group III demonstrated no significant increase in TPR, CVR, or PVR, a progressive increase of CO and CF, and preservation of SW. It is hypothesized that endotoxin shock is characterized by an initial phase characterized by an increase in resistance and decrease in flow that is not affected by an augmented venous return. However, in the intermediate and latter stages of shock, there is a progressive increase in resistance and decrease in flow, increasing impedance to left ventricular ejection that results in an imbalance between myocardial oxygen supply and demand, contributing to the observed myocardial failure. An augmented venous return, by decreasing resistance (afterload) and increasing venous return (preload) preserves cardiac output and myocardial function and thus serves as a model of left ventricular afterload reduction during the course of endotoxin shock.

Animals↗
PubMed1980

Preventive effects of theophylline on anaphylactic shock in rats.

Anaphylactic shock was induced by administration of ovalbumin to sensitized rats. Preventive effects of theophylline on anaphylactic shock were examined with regard to the relationship between cyclic AMP and prostaglandin (PG) E2 in lung tissue, and plasma histamine. During anaphylactic shock, levels of cyclic AMP content and PGE2 content in lung tissue decreased, while plasma histamine content increased. Theophylline increased levels of cyclic AMP content and PGE2 content in lung tissue, in a dose dependent manner, and pretreatment of animals with theophylline prevented the onset of anaphylactic shock. Pretreatment with indomethacin abolished the preventive effects of theophylline on anaphylactic shock, and the effect of theophylline on the cyclic AMP content. Dibutyryl cyclic AMP (DBcyclic AMP) increased PGE2 content in lung tissue, in a dose dependent manner, and also prevented the onset of anaphylactic shock. These effects of DBcyclic AMP were inhibited by the pretreatment with indomethacin, and here, cyclic AMP in lung tissue was maintained at a high level. In the group in which anaphylactic shock was prevented with these interventions, PGE2 content in lung tissue was significantly high in all cases. In addition PGE2 infusion prevented anaphylactic shock. These data suggest that theophylline increases cyclic AMP levels in lung tissue only in the presence of endogenous PG, that increased cyclic AMP content in lung tissue subsequently increases PGE2 content in lung tissue, and that the preventive effects of theophylline on anaphylactic shock result from increased PGE2 content in lung tissue.

Anaphylaxis↗
PubMed1980

Prostaglandin E2 and cyclic nucleotides during anaphylactic shock in rats.

Anaphylactic shock was induced with ovalbumin in sensitized rats and the relationship between PGE2 and cyclic nucleotides in lung tissue and plasma histamine during anaphylactic shock was studied. PGE2 level and cyclic AMP/cyclic GMP ratio decreased with this ovalbumin-challenge, and the former reached a minimum value 40 sec after the challenge while the latter reached a minimum value 20 sec later. The plasma histamine level was elevated and reached a maximum value concomitant with the minimum value in the cyclic AMP/cyclic GMP ratio. Dibutyryl cyclic AMP elevated the PGE2 level significantly and inhibited the ovalbumin-induced elevation of plasma histamine, however, this effect was abolished by the administration of indomethacin. PGE2 infusion elevated the cyclic AMP level as well as the cyclic AMP/cyclic GMP ratio, in a time-dependent manner, and inhibited the ovalbumin-induced elevation of plasma histamine during 10 min infusion. There was a significant correlation between the cyclic AMP level and the cyclic AMP/cyclic GMP ratio, both elevated by PGE2 infusion. Thus, anaphylactic elevation of the plasma histamine level results from a decrease in the levels of PGE2 in lung tissue rather than a decrease in the cyclic AMP/cyclic GMP ratio, albeit these decreases being coincident during anaphylactic shock.

Anaphylaxis↗
PubMed1978

Cardiovascular effects of isoproterenol and possible antagonistic actions of propranolol and perhexiline.

A beta-adrenergic blocking activity of perhexiline was compared with that of propanolol. In the Langendorff's preparation of rabbits, canine heart-lung preparations, open-chest dog preparations and hind-limbs of dogs, perhexiline failed to block isoproterenol-induced changes in cardiovascular functions, which were effectively blocked by propranolol. These data suggest that perhexiline is not a beta-adrenergic receptor blocking agent.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: a new proposed mechanism by the scavenging of free radicals.

Glucose, insulin, potassium (GIK: 300 g glucose + 50 U insulin + 80 mEq KC1/L) was administered to anesthetized dogs as a 30-ml bolus followed by 1.5 ml/kg/h for 2 h. Five populations were studied: control (C, n = 6); 60 min hypothermic arrest both without (I, n = 6) and with pretreatment (I + GIK, n = 6); 60 min hypothermic arrest followed by reperfusion without (R, n = 6) and with pretreatment (R + GIK, n = 6). Glycogen content declined during the ischemic and reperfusion periods whether or not GIK pretreatment was utilized. Glycogen values did not differ significantly among the four groups. GIK pretreatment significantly protected sarcoplasmic reticulum (SR) calcium uptake rates. SR Ca2+ + Mg2+ adenosine triphosphatase (ATPase) activity was unaffected in the I group, depressed in the R group, but protected by GIK pretreatment. Myofibrillar pCa-ATPase activity was significantly depressed in the I group and unaffected by GIK pretreatment. In the R + GIK group, myofibrillar pCa-ATPase activity was identical to controls at all calcium concentrations except for Vmax. In vitro, generation of the superoxide anion by a xanthine-xanthine oxidase system at pH 7.0 significantly depressed both SR calcium uptake and ATPase activity, and this depression was partially reversible by glucose. Generation of the hydroxyl free radical and pH 6.4 significantly depressed calcium uptake but not ATPase activity, and this depression was reversible with glucose + superoxide dismutase. GIK pretreatment exerts a protective effect on the excitation-contraction coupling system during hypothermic global ischemia and reperfusion. Glycogen augmentation after short-term GIK infusion was not significantly different. It is hypothesized that an additional mechanism by which GIK may protect subcellular function is by serving as a scavenger of free radicals generated during the ischemic/reperfusion process.

Adenosine Triphosphatases↗