Search PubMed⌕ Search

Biomedical subjects

S Takeo

Publications and source records attributed to S Takeo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Microsphere embolism-induced changes in presynaptic function of the cerebral cortex in rats.

The present study was undertaken to elucidate pathophysiological changes in the cortical presynaptic function, K(+)-stimulated calcium influx, noradrenaline release and noradrenaline uptake, on the 1st and 3rd days after microsphere embolism in rats. Voltage-dependent calcium channels were characterized pharmacologically using three types of calcium channel blockers, L-type (nifedipine and diltiazem), N-type (omega-conotoxin GVIA), and P-type channel (omega-agatoxin IVA) blockers. K(+)-stimulated calcium influx of the normal rat synaptosome was inhibited by 100 nM omega-agatoxin IVA, but not by 10 microM nifedipine, 10 microM diltiazem and 100 nM omega-conotoxin GVIA. Calcium influx of the cortical nerve terminals of the right hemisphere was decreased on the 1st and 3rd days after the embolism. Noradrenaline release and uptake were also decreased on the 1st and 3rd days after the embolism. However, the percent release of noradrenaline was not altered. The results suggest that P-type channels are predominant in the cerebrocortical nerve terminals in rats and that calcium influx, noradrenaline release and uptake in the cerebrocortical nerve terminals are decreased by microsphere embolism. The decrease in noradrenaline release may be mainly due to a reduction in the activity of noradrenaline uptake in cerebrocortical nerve terminals of the microsphere-embolized rat.

Animals↗
PubMed1996

Involvement of superoxide and nitric oxide in the genesis of reperfusion arrhythmias in rats.

To assess the role of reactive oxygen species and nitric oxide (NO) in the genesis of reperfusion-induced arrhythmias, the effects of reactive oxygen species scavengers and NO synthase inhibitors on the incidence of ventricular fibrillation and irreversible ventricular fibrillation (mortality) were examined. Hearts of anesthetized rats were subjected to 4 min regional ischemia followed by 4 min reperfusion. The animals were treated i.v. with superoxide dismutase, a O2- scavenger, catalase, a H2O2 scavenger, dimethylthiourea, a .OH scavenger, or NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA), NO synthase inhibitors. Superoxide dismutase (430 and 4300 U/kg/min) reduced the mortality from 93% to 43% and 57%, respectively, whereas treatment with catalase or dimethylthiourea did not affect these arrhythmias. L-NAME (0.1 and 0.3 mg/kg/min) reduced the mortality from 93% to 50% and 43%, respectively. L-NNA (0.3 mg/kg/min) reduced the mortality from 93% to 50%. This reduction by the NO synthase inhibitors was abolished by administration of L-Arg. However, L-Arg blocked neither a small increase in systolic blood pressure nor a decrease in heart rate elicited by the NO synthase inhibitors. The combinated treatment of superoxide dismutase (4300 U/kg/min) with L-NAME (0.3 mg/kg/min) reduced the mortality from 93% to 7%. These results suggest that the genesis of reperfusion-induced arrhythmias observed in this model may be in part due to O2- and NO.

Analysis of Variance↗
PubMed1996

Beneficial effects of angiotensin I converting enzyme inhibitor on post-ischemic contractile function of perfused rat heart.

The present study was undertaken to determine whether trandolaprilat, an active form of angiotensin I converting enzyme (ACE) inhibitor, may improve ischemia/reperfusion-induced contractile dysfunction and metabolic derangement of isolated rat hearts. Ischemia (25 min) and subsequent 60-min reperfusion resulted in a small recovery of post-ischemic left ventricular developed pressure (LVDP), a sustained increase in left ventricular end-diastolic pressure, an increase in the release of creatine kinase and ATP metabolites from the perfused heart, and changes in myocardial sodium, potassium, calcium and magnesium contents. Treatment with 10-100 microM of trandolaprilat for the last 10 min of pre-ischemia recovered approximately 50-90% of pre-ischemic LVDP during reperfusion, whereas that with 30-100 microM of enalaprilat restored approximately 55-65% of the pre-ischemic LVDP. Treatment with either trandolaprilat or enalaprilat at these concentrations attenuated the release of creatine kinase and ATP metabolites into the perfusate during reperfusion. Treatment with 30 microM trandolaprilat suppressed ischemia/reperfusion-induced changes in myocardial ion content. Treatment with bradykinin during the last 10 min of pre-ischemia also resulted in a post-ischemic contractile recovery with a degree similar to that of the trandolaprilat-treated hearts. E4177, an AT1-antagonist, showed no effect on ischemia/reperfusion-induced changes in cardiac parameters. The enhancement of post-ischemic contractile recovery by the ACE inhibitor was abolished by treatment with either Hoechst 140, a bradykinin (BK2) antagonist, or diclofenac, a cyclooxygenase inhibitor. These results suggest that trandolaprilat is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts and altered BK metabolism is, at least in part, involved in this effect.

Adenosine Triphosphate↗
PubMed1996

Effects of long-term treatment with trandolapril on augmented vasoconstriction in rats with chronic heart failure.

BACKGROUND: Despite the clinical relevance of angiotensin I-converting enzyme (ACE) inhibitors, their effects on impaired vascular function in patients and animals with chronic heart failure (CHF) have not been fully understood. This study was undertaken to determine whether long-term treatment with an ACE inhibitor improved the altered contractile properties of vessels from rats with CHF. METHODS AND RESULTS: Twelve weeks after coronary artery ligation, the rats were sacrificed and the isometric tension development of thoracic aorta, pulmonary artery, and mesenteric artery with and without endothelium was examined. Contractile responses to norepinephrine and prostaglandin F2 alpha were augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta and pulmonary artery segments of the rat with CHF. The contractile response to angiotensin II was augmented in endothelium-denuded mesenteric artery segments of the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd to 12th week after the operation. Treatment with trandolapril reversed the augmented contractile response of the rat with CHF to norepinephrine, prostaglandin F2 alpha, and angiotensin II almost to the levels in the sham-operated rat. CONCLUSIONS: The results demonstrate that an ACE inhibitor is capable of reversing altered vascular function in the rat with CHF, suggesting that vascular beds are possible sites of action for ACE inhibitors in the therapy for CHF.

Analysis of Variance↗
PubMed1996

Effects of delayed treatment with nafronyl oxalate on microsphere embolism-induced changes in monoamine levels of rat brain regions.

1. The present study was undertaken to examine the effects of delayed treatment with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine neurotransmitters of brain regions in the microsphere-embolized rat. 2. Microsphere embolism was induced by injecting 900 microspheres with a diameter of 48 microns into the right internal carotid artery of rats. Microsphere-embolized rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to the 5th day. Levels of monoamines and their metabolites in the cerebral cortex, striatum, and hippocampus were measured on days 3 and 5 after the operation by a high-performance liquid chromatograph with electrochemical detection. In vivo tyrosine or tryptophan hydroxylation was estimated by measurement of the accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5, the decrease in the monoamines of the right hemisphere was attenuated by nafronyl treatment except for noradrenaline on day 3. The decrease in the monoamines levels in the left hemisphere was almost completely prevented by nafronyl treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and tryptophan hydroxylation was lower than the pre-embolic value in all three brain regions. Treatment of the embolized rats with nafronyl significantly attenuated the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results suggested that treatment with nafronyl improves or attenuates changes in monoamine neurotransmitter metabolism of the brain regions impaired by microsphere embolism. The mechanisms underlying this effect may be attributed to preservation of the ability to synthesize monoamines when the brain is ischaemic or oligaemic.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Impairment of cGMP- and cAMP-mediated vasorelaxations in rats with chronic heart failure.

To elucidate pathophysiological alterations in vascular relaxation in rats with chronic heart failure (CHF), guanosine 3',5'-cyclic monophosphate (cGMP)- and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated vasorelaxations in pulmonary artery (PA) and thoracic aorta (TA) of rats were examined 12 wk after coronary artery ligation. Acetylcholine (ACh)-induced relaxation was attenuated in endothelium-intact segments of both arteries, whereas sodium nitroprusside-induced relaxation was attenuated only in endothelium-intact TA segments of rats with CHF. Vasorelaxations elicited by isoproterenol and NKH-477, a water-soluble forskolin analogue, were diminished mainly in PA segments of the CHF rat. NG-nitro-L-arginine methyl ester (L-NAME)-induced decrease in cGMP level was less in endothelium-intact TA segments of the rat with CHF (0.20 +/- 0.06 vs. 0.99 +/- 0.26 pmol/mg protein in control), suggesting that basal nitric oxide (NO) production is reduced in CHF. Treatment with L-NAME attenuated the isoproterenol-induced relaxation only in endothelium-intact TA segments in control rats but not in CHF rats. The results suggest that both cGMP- and cAMP-mediated relaxations are impaired in CHF, and a reduction of NO synthesis, presumably in endothelial cells, plays a significant role in pathophysiological alterations in vessels of rats with CHF.

Animals↗
PubMed1996

Effects of aprindine on ischemia/reperfusion-induced cardiac contractile dysfunction of perfused rat heart.

The present study was undertaken to determine whether aprindine, a class Ib antiarrythymic agent, exerts beneficial effects on ischemia/reperfusion-induced cardiac contractile dysfunction and metabolic derangement. Isolated rat hearts were subjected to 35-min global ischemia, followed by 60-min reperfusion, and functional and metabolic alterations of the heart were determined with or without aprindine-treatment. Ischemia induced a cessation of left ventricular developed pressure (LVDP), a rise in left ventricular end-diastolic pressure (LVEDP), and an increase in myocardial sodium content and a decrease in myocardial potassium content. When the hearts were reperfused, little recovery of LVDP and sustained rise in LVEDP and perfusion pressure were observed. Ischemia/reperfusion resulted in a release of ATP metabolites and creatine kinase from perfused hearts, an increase in myocardial sodium and calcium contents, and a decrease in myocardial potassium and magnesium contents. Treatment of the perfused heart with either 10 or 30 microM aprindine for the last 3 min of pre-ischemia improved contractile recovery during reperfusion and suppressed changes in myocardial ion content during ischemia and reperfusion. Treatment with the agent also attenuated the release of ATP metabolites and creatine kinase from the heart. However, treatment with high concentrations of aprindine (70 and 100 microM) improved neither cardiac contractile dysfunction, myocardial ionic disturbance nor the release of ATP metabolites and creatine kinase during reperfusion. Two possible mechanisms for the cardioprotection by the agent have been suggested: suppression of transmembrane flux of substrates and enzymes, and prevention of accumulation of myocardial sodium during ischemia.

Animals↗
PubMed1996

The role of accumulation of sodium and calcium on contractile failure of the hypoxic/reoxygenated heart.

The present study was undertaken to determine whether myocardial energy or ion levels are related to oxygen-replenishment-induced recovery of cardiac contractile force after hypoxia. Isolated rat hearts were perfused for 3 to 40 min under hypoxic conditions, followed by 45 min of reoxygenation. Hypoxia induced a cessation of cardiac contractile force, a rise in resting tension, a decrease in high energy phosphates, and an increase in lactate. Myocardial ATP, creatine phosphate (CP) and lactate reached steady-state levels after 15, 10 and 5 min of hypoxia, respectively. Hypoxic conditions in the present study also caused an increase in sodium content and a decrease in potassium content, but not changes in calcium content, along with a prolonged hypoxic period. When the hearts were perfused for more than 25 min under hypoxic conditions, no recovery of contractile force was observed following 45-min of reoxygenation. Hypoxic perfusion for more than 25 min induced an accumulation of tissue sodium content approximately 3 fold higher than the pre-hypoxic value at the end of hypoxia, and also induced a marked increase in myocardial calcium content upon reoxygenation. When tissue sodium content accumulated by less than 300% of the pre-hypoxic value, cardiac contractile function was partially reversed by reoxygenation and calcium-overload was not observed. The recovery of post-hypoxic cardiac contractility correlated with tissue sodium content during hypoxia rather than with myocardial high energy phosphate content at the end of hypoxia. These results suggest that accumulation of tissue sodium content in the hypoxic myocardium and calcium content in the reoxygenated myocardium may be indicative of hypoxia/reoxygenation-induced cardiac contractile failure.

Adenosine Triphosphate↗
PubMed1995

Long-term treatment with angiotensin I-converting enzyme inhibitors attenuates the loss of cardiac beta-adrenoceptor responses in rats with chronic heart failure.

BACKGROUND: Cardiac contractile force in response to beta-adrenoceptor agonists and beta-adrenergic receptor density are decreased in failing human hearts. The effects of angiotensin I-converting enzyme (ACE) inhibitor on cardiac responsiveness to beta-adrenergic stimulation in failing hearts are not established. The present study was undertaken to determine whether ACE inhibitor may improve cardiac beta-adrenergic responsiveness in animals with chronic heart failure (CHF). METHODS AND RESULTS: CHF was induced by left coronary artery ligation in rats. Cardiac output and stroke volume indices decreased 12 weeks after the operation. In sham-operated rats, dobutamine and isoprenaline increased cardiac output and stroke volume indices. In contrast, cardiac output and stroke volume responses to dobutamine and isoprenaline were severely blunted in the CHF rat. Cardiac beta 1-adrenergic receptor density was decreased while its dissociation constant (Kd) was not altered in the viable tissue of the left ventricle of the CHF rat, which is consistent with beta-adrenergic receptor downregulation. Cardiac norepinephrine content decreased in the CHF rats. Rats were treated orally with ACE inhibitors, 3 mg/kg trandolapril or 10 mg/kg enalapril once daily, or 5 mg/kg captopril twice daily from the 2nd to the 12th weeks after the operation. Treatment with ACE inhibitors attenuated the reduction in cardiac output and stroke volume indices and improved the inotropic response to dobutamine and isoprenaline and reversed partially the cardiac norepinephrine content in the CHF rat. ACE inhibitor treatment also attenuated the reduction in beta 1-adrenergic receptor density in the viable tissue of the left ventricle of the CHF rat. CONCLUSIONS: The results suggest that ACE inhibitor treatment attenuates the blunting of cardiac responses to beta-adrenergic agonists in the CHF rat and that one of the mechanisms underlying this effect is prevention of cardiac beta 1-adrenergic receptor downregulation.

Adrenergic beta-Agonists↗
PubMed1995

Mexiletine and lidocaine reduce post-ischemic functional and biochemical dysfunction of perfused hearts.

The present study was undertaken to determine whether class Ib antiarrhythmic agents, mexiletine and lidocaine, exert beneficial effects on ischemia/reperfusion-induced cardiac contractile dysfunction. Isolated rat hearts were subjected to 35-min global ischemia, followed by 60-min reperfusion and the functional and metabolic alterations were examined with and without mexiletine or lidocaine treatment. Ischemia/reperfusion resulted in a lack of recovery of contractile function, a sustained rise in left ventricular end-diastolic pressure and increased coronary perfusion pressure of the perfused heart during reperfusion. Contractile dysfunction was associated with increases in tissue Na+ and Ca2+ levels, decreases in K+ and Mg2+ levels, and release of creatine kinase and purine nucleosides and bases (ATP metabolites) from the heart. Treatment of the perfused heart with either 10-100 microM of either mexiletine or lidocaine during pre-ischemia resulted in an enhancement of post-ischemic contractile recovery, a suppression of changes in tissue Na+, K+, Ca2+ and Mg2+ contents and an attenuation of the release of creatine kinase and ATP metabolites in an almost concentration-dependent manner. Tissue sodium accumulation was observed at the end of ischemia, which was also attenuated by pretreatment with these agents. The prevention of Na+ overload and accompanying Ca2+ overload in cardiac cells may be the mechanism underlying the improvement of post-ischemic contractile function of perfused hearts by these agents.

Adenosine Triphosphate↗
PubMed1995

Hypoxic preconditioning in isolated rat hearts: non-involvement of activation of adenosine A1 receptor, Gi protein, and ATP-sensitive K+ channel.

Activation of the adenosine A1(A1) receptor, Gi protein, and ATP-sensitive K+ (KATP)-channel system has been shown to play an important role in the cardioprotective effects of ischemic preconditioning in dogs. The present study was undertaken to elucidate the possible involvement of this system in hypoxic preconditioning, which ameliorates injury induced by prolonged ischemia and subsequent reperfusion in perfused rat hearts. Ten minutes of hypoxic preconditioning resulted in an appreciable improvement of post-ischemic cardiac contractile recovery. This was associated with a significant reduction in the release of creatine kinase (CK) from reperfused hearts. Hypoxic preconditioning shortened the time to ischemic contracture onset and prevented a further rise in left ventricular end-diastolic pressure (LVEDP) during reperfusion. Neither the selective A1 receptor antagonist, 8-cyclopentyltheophylline (CPT) nor the KATP channel blocker, glibenclamide, altered the beneficial effects of hypoxic preconditioning. In vivo pretreatment with an inhibitor of Gi protein, pertussis toxin (PTX), also did not diminish the preconditioning effect. The results suggest that, although hypoxic preperfusion ameliorates post-ischemic contractile dysfunction, neither the activation of the A1 receptor, nor the opening of the KATP-channel, nor transduction through Gi protein are involved in the post-ischemic functional recovery of hypoxic preconditioning in the perfused rat heart.

Adenosine Triphosphate↗
PubMed1995

The effects of long-term treatment with eicosapentaenoic acid and docosahexaenoic acid on hypoxia/rexoygenation injury of isolated cardiac cells in adult rats.

N-3 polyunsaturated fatty acids have been epidemiologically demonstrated to decrease the incidence of ischaemic heart disease. The present study was undertaken to examine the effects of long-term treatment with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on hypoxia/reoxygenation injury of isolated adult rat cardiomyocytes. Rats, fed with standard rat chow, were treated with 100 to 1000 mg/kg/day EPA or 1000 mg/kg/day DHA for 4 weeks and their cardiomyocytes were isolated by collagenase treatment. The cardiomyocytes, approximately 90% of which were rod-shaped, were subjected to 150-min hypoxia/15-min reoxygenation, and their survivals at the ends of hypoxia and reoxygenation were determined. Treatment with either 1000 mg/kg/day of EPA or DHA resulted in a significant increase in the survival of the cardiomyocytes (39.9 +/- 1.1 and 38.3 +/- 3.0%, n = 14 and 8, respectively v 26.7 +/- 1.6%, n = 8, for untreated group). Treatment with EPA increased eicosapentaenoic (377% increase), oleic (25% increase) and linoleic acid (37% increase) contents in the myocardial total phospholipids without changes in the total phospholipid content, whereas treatment with DHA did not increase DHA incorporation into the myocardial phospholipids. The results suggest that EPA and DHA protect the myocardial cells against hypoxia-reoxygenation-induced injury. Although alterations in myocardial phospholipid composition were observed by treatment with EPA or DHA, the primary mechanism underlying the benefit of EPA or DHA intake is unlikely to be related to increased incorporation of their own fatty acids into the myocardial phospholipids, or the mechanism may be different in each n-3 unsaturated fatty acid employed.

Animals↗
PubMed1995

Biliary secretion of antibody to dextran following oral immunization with dextran B512.

Anti-dextran in bile was induced to high levels by oral immunization with dextran B512. IgM anti-dextran were dominant in serum, whereas IgG anti-dextran was dominant in bile. The binding properties of these IgM and IgG antibodies were different, as determined by ELISA with several dextrans. Splenocytes produced equal amounts of IgG and IgM antidextran but cells from mesenteric lymph nodes (MLN) and Peyer's patches produced mainly IgG anti-dextran. Differences were observed among different strains of mice in their ability to produce anti-dextran in serum and bile upon immunization with dextran. BALB/c mice, which are intermediate responders in terms of their serum antibody levels, produced high levels of anti-dextran in bile. C3H/He and C57BL/6, which are high responders in terms of serum antibody levels, had intermediate responses in bile. DBA/2, which are low responders in terms of serum antibody levels, showed low responses in bile. The results provide further evidence of the existence of anti-dextran producing cells. These results indicate that B cells in systemic and mucosal-associated lymphoid tissues from BALB/c, C3H/He, C57BL/6 and DBA/2 mice respond differently to oral immunization with dextran B512.

Administration, Oral↗
PubMed1995

Effects of long-term therapy with ACE inhibitors, captopril, enalapril and trandolapril, on myocardial energy metabolism in rats with heart failure following myocardial infarction.

Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation. HF was induced by permanent occlusion of the left coronary artery of the rat at 2 mm from its origin. Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, attenuated the rise in left ventricular end-diastolic pressure, an indirect marker of preload, and diminished the reduction in cardiac output and stroke volume indices of the HF animal. Treatment also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energy phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sham-operated animals, treatment with the ACE inhibitors reduced mean arterial pressure and left ventricular systolic pressure, but not metabolic variables concerning myocardial energy metabolism. The present results provide evidence that ACE inhibitor therapy improves cardiac function and myocardial energy metabolism of experimental animals with chronic heart failure. The mechanism underlying the benefit of long-term treatment with ACE inhibitors is probably attributable to recovery or preservation of the mitochondrial function and reduction in preload.

Adenine Nucleotides↗
PubMed1995

Reperfusion at reduced flow rates enhances postischemic contractile recovery of perfused heart.

The effects of reperfusion at reduced flow rates on postischemic cardiac contractile function were examined in perfused rat hearts. Isolated hearts were subjected to 35-min ischemia followed by reperfusion at the preischemic flow rate (9.0 ml.g-1.min-1; ordinary flow rate) or at reduced flow rates (0.9-8.1 ml.g-1.min-1). Reperfusion at ordinary flow rate did not generate any left ventricular developed pressure (LVDP), whereas reperfusion at reduced flow rates (0.9-7.2 ml.g-1.min-1) elicited 13-57% of initial contractile force at reperfusion's end; optimal recovery occurred at 3.6 ml.g-1.min-1 (reduced flow rate). Reduced flow rate reperfusion attenuated ischemia-reperfusion-induced increase in left ventricular end-diastolic pressure (LVEDP) and perfusion pressure (PP), alteration in tissue Na+, K+, Ca2+, and Mg2+, release of creatine kinase and ATP metabolites, and development of triphenyltetrazolium chloride-unstained areas. Enhanced postischemic LVDP recovery was inversely related to higher coronary PP at the initial stage (4 min) of reperfusion (r = -0.763). The benefit of reduced flow rate reperfusion could not be attributed to rate of calcium delivery to the heart, formation of oxygen free radicals in myocardium, endothelium-dependent coronary artery dilation, or LVDEP reduction. Enhancement of postischemic LVDP recovery was associated with attenuation of ischemia-reperfusion-induced increases in myocardial sodium and calcium; failure of postischemic LVDP recovery was accompanied by an increase. Reduction in sodium and calcium overload may underlie the beneficial effects of reduced flow rate reperfusion in ischemic-reperfused heart.

Adenosine Triphosphate↗
PubMed1995

Changes in striatal dopamine metabolism after microsphere embolism in rats.

BACKGROUND AND PURPOSE: Dopamine plays an important role in striatal function. The present study was undertaken to elucidate the pathophysiological changes in striatal dopamine metabolism after microsphere embolism. METHODS: Microspheres (48 microns) were injected into the right internal carotid artery of rats. Extracellular levels of dopamine and its metabolites were measured by in vivo microdialysis with the aid of high-performance liquid chromatography. In vivo striatal tyrosine hydroxylation and turnover (catabolism) rate of dopamine were estimated on the first and third days after the embolism. These were estimated by measuring tissue dopa or dopamine content in the presence of either an aromatic L-amino acid decarboxylase inhibitor or a tyrosine hydroxylase inhibitor, respectively. RESULTS: In the microdialysis study, a 190-fold increase in the release of dopamine from the right striatum was observed 40 minutes after microsphere embolism, whereas the striatal dopamine metabolites decreased during the first 180 minutes after the embolism. Microsphere embolism decreased the striatal dopamine content throughout the experiment (28 days), whereas it increased tissue dopamine metabolites on the first day, followed by a decline in the metabolites on the third day or later. The in vivo turnover rate of dopamine decreased both on the first and third days, whereas the in vivo tyrosine hydroxylation decreased only on the third day after the embolism. CONCLUSIONS: The results suggest that microsphere embolism induces severe damage to striatal dopaminergic metabolism 3 to 28 days after the embolism. Dopamine synthesis may be more resistant to the embolism-induced ischemic insults than its catabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Diminished responsiveness to cardiac beta 1-adrenoceptor agonists in rats with chronic heart failure following myocardial infarction.

The present study was undertaken to determine whether cardiac response to beta 1-adrenergic agonists is altered in rats with chronic heart failure (CHF), and whether this alteration is related to beta-adrenergic receptor down-regulation in the viable tissue of the left ventricle of these rats. For this purpose, the cardiac response to denopamine, a selective beta 1-adrenergic agonist, and the change in cardiac beta-adrenoceptor density were examined in rats with CHF. A non-selective beta-adrenergic agonist, isoprenaline, was also examined as a comparison. Cardiac output and stroke volume indices were reduced 12 weeks after left coronary artery ligation, suggesting that CHF had developed at this time. Denopamine (2, 4 and 8 micrograms/kg i.v.), and isoprenaline (0.01 microgram/kg i.v.) increased the cardiac output and stroke volume indices in sham-operated rats, whereas such increases were attenuated in the CHF rat. The cardiac beta-adrenergic receptor density, measured by [3H]CGP-12177 binding assay, was reduced in homogenates and microsomal membranes in the viable tissue of the left ventricle of the CHF rat (homogenates: 29% reduction, microsomal membrane: 23% reduction). These results suggest that the cardiac responsiveness to denopamine is diminished in the CHF rat and this alteration is accounted for, in part, by a decrease in cardiac beta-adrenoceptor density.

Adrenergic beta-1 Receptor Agonists↗