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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 1,225 records · Page 68Linked to original sources
PubMed1984

Differential effects of halothane on airway nerves and muscle.

Effects of halothane on the excitation-contraction coupling or neuro-effector transmission in the dog tracheal muscle were observed in vitro in an attempt to clarify the cellular mechanisms involved in anesthetic-induced bronchodilation. Double sucrose gap, microelectrode, and tension recording methods were used. Application of halothane evoked an initial induction of phasic contraction with no alteration in the electrical membrane properties, and secondarily a reduction in muscle tone with membrane hyperpolarization. Halothane suppressed the amplitude of the twitch contractions evoked by indirect (nerve mediated) or direct muscle stimulation, the degree of suppression being greater with the former stimulation. The threshold membrane depolarization required for the generation of tension development was increased. In the presence or absence of TEA, halothane completely suppressed the generation of an action potential or a local response in the muscle membrane, following stimulation by outward current pulses. Therefore, halothane has complex actions on Ca++ economy in the tracheal smooth muscle cell, i.e., initial release of Ca++ from the store sites followed by inactivation or a reduction in free calcium ions in the cytoplasm, and/or suppression of the influx of Ca++ across the cell membrane. Low concentrations of halothane (less than or equal to 1%) suppressed the amplitude of excitatory junction potential (EJP) without altering the membrane potential, membrane resistance, or muscle sensitivity to acetylcholine. Therefore, this anesthetic probably suppresses the release of transmitter from the nerve terminals. Halothane also suppressed the facilitation phenomena of EJP during repetitive nerve stimulation. These direct inhibitory effects of halothane on smooth muscle cells and excitatory neuro-effector transmission could account for the potent bronchodilator action of this anesthetic.

Action Potentials↗
PubMed1984

Plasma lipid peroxides and alpha-tocopherol in critically ill patients.

Plasma lipid peroxide measured as thiobarbituric acid reactive substances (TBARS) and alpha-tocopherol levels in 24 critically ill patients were compared with those of control subjects. The mean plasma alpha-tocopherol level was significantly lower and the mean TBARS level was significantly higher in critically ill patients. Eight ICU patients developed disseminated intravascular coagulation (DIC); the mean TBARS level during DIC was significantly above the mean pre-DIC level. These results indicate that lipid peroxidation may contribute to the development of DIC in critically ill patients.

Adolescent↗
PubMed1984

Anti-arrhythmic effects of (-)-carnitine chloride and its acetyl analogue on canine late ventricular arrhythmia induced by ligation of the coronary artery as related to improvement of mitochondrial function.

Using the two-stage coronary ligation method, first described by Harris, (1950), anti-arrhythmic effects (AAE) of (-)-carnitine chloride (LCC) and acetyl (-)-carnitine chloride (ALCC) were studied in conscious unrestrained dogs in comparison with those of disopyramide (D). Two-stage ligation of the coronary artery resulted in a significant decrease in the myocardial free carnitine content. Intravenous administration of LCC (300 mg kg-1) and D (5 mg kg-1) suppressed the ventricular arrhythmia induced by coronary ligation after 24 hours. ALCC (300 mg kg-1) was found to be less potent. An improvement of the mitochondrial function (respiratory control index (RCI) and oxidative phosphorylation rate (OPR) ) was noted with LCC and ALCC and there was a linear correlation between AAE expressed as reduction of arrhythmic ratio and improvement in the OPR, whereas there was no improvement in mitochondrial function after D. Plasma carnitine concentration was increased after administration of LCC, attaining the value of around 8 mM at 10 min after 300 mg kg-1. At 60 min, the plasma carnitine concentration was still about half as high as at 10 min. After ALCC, both acetyl carnitine and free carnitine were found in the plasma. The concentration of the former was decreased after attaining a peak value of around 0.2 mM at 10 min, while the plasma concentration of free carnitine was gradually increased. The anti-arrhythmic effects of LCC and ALCC were ascribed to the improvement of mitochondrial oxidative phosphorylation, while effects other than the improvement of the mitochondrial activity were suggested as mechanisms of anti-arrhythmic effects of D.

Acetylcarnitine↗
PubMed1984

A patch-clamp study of the partial agonist actions of tubocurarine on rat myotubes.

Single channels activated by (+)-tubocurarine (curare) were recorded from rat myotubes using the patch-clamp technique. The agonist-like action of curare does not result from a contaminant molecule, as the same effects were observed with curare purified by high-performance liquid chromatography. A curare-activated channel can adopt two levels of conductance: full (F) or partial (P). The F state has a slope conductance of 40 pS (identical to that of the acetylcholine (ACh)-activated channel) and the P state has a conductance of 13 pS. At low concentrations of agonist (ACh or curare), the distribution of channel open times is biphasic. The briefer channels may result from the binding of a single agonist molecule whereas the longer-lived channels probably occur following the binding of two agonist molecules. The mean open time of the F state decreases with increasing curare concentration. It is shown that band-width limitations are likely to account for only a very small part of this observed reduction. In contrast, the mean open time of the P state is independent of the concentration of curare. A simple interpretation is that the F state is susceptible to channel blockade by curare, whereas the P state is not. The P state preceded the F state almost as often as it followed the F state; it can also be observed separately from the F state. The fraction of events including a P state increases from about 4% in the presence of 1 microM-curare to 30% at 100 microM-curare. This fraction is also increased by hyperpolarization. When the curare concentration is increased, the F-state frequency first increases and then decreases at higher concentration. This frequency is also decreased by hyperpolarization. The decrease in F-state frequency is probably related to channel blockade by curare; it cannot be wholly accounted for by problems associated with limited time resolution. A synthetic analogue of curare, (+)- tubocurine dimethiodide presents an agonist activity similar to that of curare but with a faster closing rate for both F and P states. The various actions of curare are summarized in two possible models where the P state is interpreted as either a partially open channel or a channel which is partially blocked.

Acetylcholine↗
PubMed1984

Prostaglandin-induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue.

In an attempt to elucidate the possible roles of endogenous prostaglandins on the neuro-effector transmission in the dog trachea, effects of a prostaglandin antagonist (1-acetyl-2-[8-chloro-10, 11- dihydrobenz (b.f) (1.4) oxazepine-10-carbonyl]hydrazine (SC-19220] on the electrical and mechanical properties of smooth muscle cells and on neuro-effector transmission in the smooth muscle layer were studied by means of micro-electrode, double sucrose-gap, and tension recording methods. The levels of prostaglandins in the perfusate from the dog tracheal tissue were also determined using radioimmunoassay. Excitatory junction potentials (e.j.p.s) and twitch tension evoked by electrical field stimulation with short pulse duration (50-100 microseconds), which were abolished by tetrodotoxin (10(-7) M) or atropine (5 X 10(-6) M), showed gradual and continuous reduction in amplitude during superfusion with normal Krebs solution. Reduction in the amplitude of e.j.p.s occurred with no change in the membrane potential or membrane input resistance. SC-19220 (3.1 X 10(-5) M) did not modify the membrane potential, membrane input resistance or the sensitivity to acetylcholine of the smooth muscle cells. Yet, with application of SC-19220 (3.1 X 10(-6) M), gradual and continuous reductions in the amplitude of e.j.p.s and twitch contractions were no longer observed. With an increased concentration (3.1 X 10(-5) M), e.j.p.s and twitch contractions with a constant amplitude were obtained after the initial increase in the amplitude. When the amplitude of twitch contractions was stabilized by treatment with indomethacin (10(-5) M), low concentrations (10(-12) to 10(-10) M) of prostaglandin E2 (PGE2) or prostaglandin F2 alpha (10(-8) to 10(-6) M) markedly suppressed the amplitude of the twitch contractions. In some muscle preparations (ten out of twenty-two preparations examined), SC-19220 (3.1 X 10(-6) to 3.1 X 10(-5) M) produced a sustained contraction of the muscle, which was suppressed by atropine (5 X 10(-6) M) or PGE2 (10(-8) M). Following pre-treatment of the tissue with atropine (5 X 10(-6) M), SC-19220 did not evoke contracture. In the resting condition, 10-40 ng g-1 wet wt. tissue min-1 PGE or PGF was released into the perfusate from the tracheal muscle tissue of the control dog.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1984

Hypervitaminosis A: a contributing factor to anemia in regular dialysis patients.

In order to evaluate the toxicity of hypervitaminosis A in regular dialysis patients, the relationships between the plasma levels of vitamin A, retinol binding protein (RBP), prealbumin (PA), and biochemical parameters were studied in 47 patients. Plasma vitamin A levels were inversely correlated with hematocrit (r = -0.5), which was also significantly correlated with RBP/vitamin A ratio (r = 0.61). Immunoreactive parathyroid hormone (i-PTH) and very low density lipoprotein (VLDL) were inversely related to RBP/vitamin A and RBP/PA ratios. These findings suggest that a raised plasma vitamin A level in regular dialysis patients contributes to anemia and hypervitaminosis A toxicity.

Adult↗
PubMed1984

Developmental changes in mitochondrial components in liver of newborn rats.

Chronological studies on the respiratory function and membrane components of newborn rat liver mitochondria revealed that perinatal mitochondria retained considerably well-coupled oxidative phosphorylation that functioned in sites II and III prior to site I. The ratio of protein to phospholipid contents (mg/mumol) was low in these mitochondria, in which phospholipids were characterized by their high phosphatidylethanolamine contents (43% of the total phospholipids) and low cardiolipin contents (6% of the total), as compared to those of the adult. The fatty acid composition in major phospholipid species was also different from those of the adult. These characteristics altered with development, and the carbamylphosphate synthetase contents markedly increased from 12 to 20% of the total polypeptides in 10 days postnatal time. From these results structural and functional completion of mitochondria accompanying development is discussed from a mitochondrial biogenesis viewpoint.

Animals↗
PubMed1984

Centrally-induced vasopressor responses to sodium-potassium adenosine triphosphatase inhibitor, ouabain, may be mediated via angiotensin II in the anteroventral third ventricle in the brain.

Central cardiovascular effects of the sodium-potassium adenosine triphosphatase (Na+, K+-ATPase) inhibitor, ouabain, were investigated by injecting it intracerebroventricularly (ICV) using conscious Wistar rats. Ouabain, 0.1-10 micrograms injected ICV, produced dose-related pressor responses attaining peak elevations after about 5 min. To investigate the underlying mechanisms of these central pressor responses, angiotensin II blockers were injected ICV before the injections of ouabain. 1-Sar, 8-Ile angiotensin II (ang IIa), 50 micrograms, given 3 min before the ouabain, abolished the pressor responses to ouabain, 5 micrograms. Angiotensin I converting enzyme inhibitor (CEI, captopril), 100 micrograms, also significantly attenuated the pressor responses to ouabain. Since previous results with ICV injections of ouabain suggested that the pressor responses are mediated via a release of brain angiotension II, and the site of action of brain angiotensin II is believed to be the anteroventral third ventricle (AV3V) area of the brain, ICV injections of ouabain were repeated using rats whose AV3V areas had been destroyed electrically. The pressor responses were smaller in the AV3V lesioned rats than in sham-operated rats. The abdominal sympathetic nerve activity was recorded using three conscious, normotensive Wistar rats. ICV injections of ouabain, 5 micrograms, elicited pressor responses as described above and these were accompanied by a corresponding increase in the nerve firing, lasting for 5-7 min. These responses were again abolished by pretreatment with an angiotensin II antagonist. These results suggest that centrally administered ouabain elicits vasopressor responses which increase peripheral sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1984

KCl inhibits hypothalamic activity to attenuate hypertension in DOCA-salt rats.

Potassium supplementation attenuated the development of hypertension in DOCA-salt rats but did not affect blood pressure in control rats. However, it caused a decrease in body weight in both groups of rats. Sympathetic nerve and pressor responses either to electrical stimulation of the hypothalamus or to intracisternal injections of hypertonic NaCl were enhanced in DOCA-salt rats but were normalized by KCl supplementation. Since the pressor responses to injected norepinephrine or tyramine remained unaltered by KCl treatment, a peripheral inhibition of cardiovascular reactivity was considered unlikely. Pretreatment with methyclothiazide also attenuated the elevation in blood pressure but did not affect the responsiveness to hypothalamic stimulation; hence increased natriuresis or diuresis alone could not account for the effects induced by KCl. These findings are consistent with the conclusion that KCl supplementation attenuates the development of DOCA-salt hypertension in rats by acting on the central nervous system to reduce sympathetic output.

Anesthesia↗
PubMed1984

Centrally induced vasopressor and sympathetic nerve responses to carbachol in rats.

Blood pressure rose when carbachol was injected into the cerebral ventricles in conscious rats, but the heart rate fell. When rats were later anesthetized with urethane to allow recording of abdominal sympathetic nerve activity, carbachol injected similarly produced the following biphasic responses: initial vasodepression followed by a sustained pressor phase accompanied by corresponding changes in peripheral sympathetic nerve activity. The heart rate was transiently suppressed following the injection. Spinal section abolished the initial hypotensive phase and accompanying bradycardia and made the response purely pressor. By contrast, intravenous injections elicited purely vasodepressor responses. Thus, carbachol administered centrally caused vasopressor responses possibly via both activation of sympathetic vasomotor centers and a release of pituitary hormones. Since anesthesia attenuated the pressor responses and made them biphasic, these results indicate that central cholinergic mechanisms are inhibited during anesthesia and that a sympatho-inhibitory mechanism of cholinergic receptors exists behind the pressor responses, as disclosed during anesthesia.

Anesthesia↗
PubMed1984

The role of prostaglandins in the regulation of blood pressure with special reference to vascular reactivity.

The role of prostaglandins (PGs) in the regulation of blood pressure was analysed from the point of view of vascular reactivity to PGs and also of PG-induced modulation of pressor response. The vasodepressor effect of PGE1 was more sensitive in the patients with essential hypertension than in the normotensive subjects. In the normotensive subjects or in rats, pressor response to norepinephrine was modulated by PGE1, enhanced under treatment with indomethacin, an inhibitor of PG biosynthesis, and suppressed under an infusion of PGE1. These results indicate that pressor response to norepinephrine is modulated by exogenous and endogenous PGs. The PG-induced modulation disappeared after chemical sympathectomy, suggesting that the PG-induced modulation of pressor response is regulated by the sympathetic nervous system. In sympathetic neurotransmission, PGs could play an important role in the regulation of norepinephrine release. Renal content of norepinephrine was reduced under treatment with indomethacin, indicating an enhanced release of norepinephrine and an enhanced turnover of norepinephrine in the kidneys under treatment with indomethacin. These results suggest that a deficient state of PG may enhance the pressor response and norepinephrine release. As there is much evidence indicating that the reduction of PG synthesis in patients and animals with hypertension, vascular reactivity to PGs and PG-induced modulation of pressor response may play significant roles in the regulation of blood pressure and could be causal factors of hypertension.

Adult↗
PubMed1984

Effect of pacemaker sites on contractile forces of the local myocardium and blood flow in the major branches of the left coronary artery in anesthetized open-chest dogs.

Decreased cardiac performance during ventricular tachycardia or ventricular pacing has been ascribed to the lack of synchrony due to altered ventricular contraction. However, the direct effect of the pacemaking site on blood flow in the major coronary arterial branches and on regional contractile forces has not been adequately examined. In this investigation, twelve dogs were used to assess coronary flow in the left anterior descending (LAD) and circumflex coronary arteries (LCx) and the regional myocardial function in response to ectopic electrical pacing. The sites were the outflow tract of the right ventricle (RV pacing), the anterior left ventricular wall supplied by the LAD (LAD pacing), and the lateral wall perfused by the LCx (LCx pacing). Strain gauge arches were transmurally fixed to myocardial segments of the anterior and lateral walls of the left ventricle. The mechanical forces generated were measured while simultaneously recording blood flow in the LAD and LCx. RV pacing diminished developed-tension similarly in both areas. LAD flow was further decreased during anterior pacing as was the developed-tension in the LAD supplied area. A similar relationship was observed between LCx flow and developed-tension in the LCx area during lateral pacing. Compared to RV pacing, anterior pacing did not affect LCx flow and local myocardial force in the lateral wall of the left ventricle, and lateral pacing did not cause further changes in LAD flow and anterior myocardial function. The decrements in blood flow were closely related to decreased myocardial function (p less than 0.01). These findings indicate that ventricular pacing decreases ventricular performance with attenuated regional myocardial function at the pacing area, in addition to causing altered ventricular contraction sequence.

Animals↗
PubMed1984

Simple technique for measuring regional contractility by a modified strain guage arch.

A simple modification of a commercially available gauge arch, namely the addition of pins to effect mechanical couplings to heart muscle rather than suturing, results in an isometric myocardial force sensor which is easy to insert, stable and relatively atraumatic to the myocardium. Compressing the pins by means of a machinist's vernier caliper which is removed after the sensor is implanted, insures controlled muscle stretch. Tests in open-chest dogs show that force sensed by this gauge is little affected by changes in heart rate, left ventricular end-diastolic pressure or aortic pressure, but faithfully reflects the inotropic effects of isoproterenol or propranolol. Thus, the modified strain gauge arch is sensitive to changes in contractility but not to changes in preload or afterload.

Animals↗
PubMed1984

Retardation of the development of hypertension in DOCA-salt rats by renal denervation.

To determine the importance of the renal nerves in DOCA-salt hypertension, either renal denervation or a sham-operation was carried out on both DOCA-salt-treated and non-DOCA-treated rats. The systolic blood pressure of the non-DOCA rats remained within normotensive levels, in which the difference in blood pressure levels between the renal denervated and the sham-operated groups was not significant. On the other hand, the blood pressure of the rats treated with DOCA, and having intact renal nerves, began to rise by the end of the first week and rose consistently thereafter, whereas, in the renal denervated DOCA-salt rats, the blood pressure started to rise by the second week and then proceeded to increase gradually. The differences between the sham and the denervated rat groups were significant throughout the four weeks. The mean arterial pressure, directly measured from the caudal artery of conscious rats during the fourth week of this study, was 166 +/- 7 mmHg in the sham-operated and 129 +/- 4 mmHg in the renal-denervated rats (the data having an 1% significant difference). To test the effects of renal denervation on the natriuresis, pentobarbital-anesthetized rats were infused intravenously with physiological saline. The renal denervated rats which had received DOCA excreted more sodium than did the sham-operated rats. When the rats were later anesthetized with urethane to allow intracisternal injections of hypertonic saline, the mean blood pressure in renal denervated rat groups was again lower than that of the sham-denervated rat groups. However, subsequent intracisternal injections of 5% saline produced similar pressor responses as well as tachycardia in both DOCA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1984

Augmented central cholinergic mechanisms in spontaneously hypertensive rats. Involvement of deranged noradrenergic mechanisms in the brain.

Intracerebroventricular (ICV) injections of carbachol produced biphasic blood pressure responses consisting of initial vasodepression of short duration followed by a sustained pressor phase, which were accompanied by corresponding changes in sympathetic nerve activity in normotensive outbred-Wistar rats (NT) under urethane-anesthesia. In both normotensive Kyoto Wistar rats (WKY) and spontaneously hypertensive rats (SHR), on the other hand, carbachol elicited purely pressor responses, and accompanying sympathetic nerve activity was little affected. The magnitude of the pressor responses was larger in SHR than in WKY or NT rats. Spinal sectioning did not affect the magnitude of the pressor responses. Vasopressor responses to intravenous injections of arginine-vasopressin were not significantly different between WKY and SHR. These results indicate that carbachol injected intracerebroventricularly produces vasopressor effects mainly by releasing pituitary hormones, probably vasopressin, and that augmented pressor responses in SHR may be due to excessive release of vasopressin. When central noradrenergic neurons had been destroyed with ICV injections of 6-hydroxydopamine in both NT and WKY rats, carbachol-induced vasopressor responses were markedly augmented and resulted in responses similar to those of SHR. These findings indicate that central noradrenergic vasodepressive neurons are deficient and that the augmented vasopressor responses to carbachol resulted from deranged central noradrenergic mechanisms in SHR.

Animals↗
PubMed1984

Centrally-induced vasopressor responses to ouabain are augmented in spontaneously hypertensive rats.

Dihydroxyouabain (ouabain), 1.0-10 micrograms, per rat, injected intracerebroventricularly, produced dose-related vasopressor responses accompanied by corresponding increases in abdominal sympathetic nerve activity in 16 weeks old Wistar (NT) rats anesthetized with urethane. The heart rate then also increased, dose-dependently, to ouabain injected in doses up to 10 micrograms. However, 100 micrograms produced arrhythmia resulting in bradycardia. Pressor effects were appreciable within one minute after the ouabain injection, but did not become maximal until between 7-10 min later. Either the removal of sympathetic vasomotor tone by surgical section of the spinal cord or intravenous pretreatment with a vasopressin antagonist significantly reduced the vasopressor responses in the NT rat. Ouabain, 10 micrograms, injected intraventricularly in 16 weeks old Kyoto Wistar rats produced similar cardiovascular responses to those in the NT rat, but the magnitude of the blood pressure responses, along with the heart rate and sympathetic responses, was larger in SHR than in WKY. These results suggest that dihydroxyouabain acts centrally to elevate the blood pressure by increasing not only the sympathetic discharge but also, perhaps, the secretion of vasopressin. In light of previous studies showing that SHRs exhibit both sympathetic hyperactivity and hypersecretion of vasopressin, the present results suggest that their enhanced responsiveness to ouabain could result from both the sympathetic hyperactivity and an enhanced vasopressin release as a result of the centrally injected ouabain.

Animals↗