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Biomedical subjects

M Endoh

Publications and source records attributed to M Endoh.

At least 109 records · Page 6Linked to original sources
PubMed1998

Relationship between the increase in Ca2+ transient and contractile force induced by angiotensin II in aequorin-loaded rabbit ventricular myocardium.

OBJECTIVES: Pieces of evidence have been accumulating that imply a crucial role of angiotensin II (Ang II) in initiation and progress of heart failure, but the signalling processes subsequent to Ang II receptor activation in cardiac myocytes are complex and still controversial. We examined the effects of Ang II on the relationship between the intracellular Ca2+ transient and isometric contraction in mammalian ventricular myocardium. METHODS: Isolated rabbit ventricular papillary muscle was loaded with the Ca2+ sensitive bioluminescent protein aequorin and electrically stimulated at a rate of 0.5 Hz at 37 degrees C. RESULTS: Ang II (10(-8)-10(-6) M), in the presence of bupranolol (3 x 10(-7) M) and prazosin (10(-7) M), elicited a positive inotropic effect (PIE) in association with an increase in the peak Ca2+ transient. The maximal PIE of Ang II was about 30% of the isoproterenol-induced maximum (ISOmax), while the maximal increase in the peak Ca2+ transient induced by Ang II was only 7% of ISOmax. Ang II tended to prolong the duration of contraction (both time to peak force and relaxation time) but did not produce a discernible change in the duration of Ca2+ transient. The relationship between the amplitude of Ca2+ transient and peak force was shifted to the left by Ang II, as compared with the relationship for elevation of [Ca2+]o (2.5-15.0 mM). The PIE and the increase in the amplitude of Ca2+ transient induced by Ang II were abolished by a selective angiotensin type 1 (AT1) receptor antagonist losartan (10(-5) M) but were not affected by a selective AT2 receptor antagonist PD123319 (10(-6) M). CONCLUSIONS: These results indicate that Ang II elicits a PIE through a dual mechanism via activation of AT1 receptors in rabbit ventricular myocardium: by an increase in the amplitude of Ca2+ transient; and in addition by an increase in the myofilament Ca2+ sensitivity.

Adrenergic alpha-Antagonists↗
PubMed1998

Endothelin: receptor subtypes, signal transduction, regulation of Ca2+ transients and contractility in rabbit ventricular myocardium.

Endothelin (ET) isopeptides, ET-1, ET-2 and ET-3, elicit a positive inotropic effect (PIE) in association with a negative lusitropic effect, essentially with identical efficacies and potencies in the isolated rabbit papillary muscle, but with different concentration-dependent properties. Pharmacological analysis indicates that the PIE of ET-1 is mediated by an ETA2 subtype that is less sensitive to BQ-123 and FR139317, whereas the PIE of ET-3 is mediated by an ETA1 subtype that is highly sensitive to these ETA antagonists. ETs increased the amplitude of intracellular Ca2+ transient (CaT) in indo-1 loaded rabbit ventricular myocytes, but the increase was much smaller than that produced by elevation of [Ca2+]o or isoproterenol for a given extent of PIE, an indication of increased myofibrillar Ca2+ sensitivity. ETs stimulate phosphoinositide (PI) hydrolysis, which leads to production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Evidence for the role of IP3-induced Ca2+ release in cardiac E-C coupling is tenuous. Generation of IP3 induced by ET-1 was transient and returned to the baseline level when the PIE reached an elevated steady level. Protein kinase C (PKC) that is activated by DAG and also via other pathways triggered by ETs stimulates Na+-H+ exchanger to lead to an increased [Na+]i and alkalinization. The former may contribute to an increase in the amplitude of CaT through Na+-Ca2+ exchanger, and the latter, to an increase in myofibrillar Ca2+ sensitivity. A number of PKC inhibitors, such as staurosporine, H-7, calphostin C and chelerythrine, consistently and selectively inhibited the PIE of ET-3 without affecting the PIE of isoproterenol and Bay k 8644. The maximum inhibition was 20-30% of the total response. A Na+-H+ exchange inhibitor, [5-(N-ethyl-N-isopropyl) amiloride (EIPA)] or a Ca2+ antagonist, verapamil, could not completely inhibit the PIE of ET-3, but the combination of both inhibitors totally abolished the PIE of ET-3. These findings indicate that activation of PKC and subsequent activation of Na+-H+ exchanger and/or L-type Ca2+ channels may play a crucial role in the cardiac action of ET isopeptides in the rabbit ventricular myocardium.

Animals↗
PubMed1998

Effect of KRN4884 on lipid metabolism in hyperlipidemic rats.

1. KRN4884 is a novel pyridinecarboxamidine type potassium channel opener. 2. To determine whether KRN4884 affects lipid metabolism, we investigated its effects on serum lipid levels by using two types of hyperlipidemic rats: genetically hyperlipidemic obese Zucker rats and diet-induced hyperlipidemic rats fed a high fat diet. KRN4884 dose dependently decreased systolic blood pressure in Zucker rats. 3. Oral administration of KRN4884 (1-10 mg/(kg day) for 14 days dose dependently reduced serum triglyceride levels in Zucker rats. The reductions in serum triglyceride were associated with reductions in triglyceride in chylomicron and very low density lipoprotein. 4. KRN4884 produced no change in serum insulin and glucose levels in Zucker rats. 5. KRN4884 exhibited a similar triglyceride lowering effect in diet-induced hyperlipidemic rats. 6. These results suggest that KRN4884 has a beneficial effect on serum triglyceride levels as well as a hypotensive effect.

Animals↗
PubMed1998

Spontaneous shrinkage of lumbosacral lipoma in conjunction with a general decrease in body fat: case report.

OBJECTIVE AND IMPORTANCE: We describe a rare case of a lumbosacral lipoma that shrank spontaneously in parallel to a general loss of body fat. Although early prophylactic surgery is generally recommended for lumbosacral lipomas, the observation made in this case may provide an important implication regarding the conservative management of this disorder. CLINICAL PRESENTATION: A 9-year-old male patient with a subcutaneous lipoma at the sacral level was found to have a lumbosacral lipoma in the spinal canal and tethered spinal cord, as revealed by magnetic resonance imaging. The patient showed no neurological or urological deficits, except for a mild pes cavus deformity. INTERVENTION: Follow-up magnetic resonance imaging performed 4 years later revealed a significant decrease in the size of the lumbosacral lipoma. The patient became very thin and showed no neurological deterioration during the follow-up period. The shrinkage of the lipoma was considered to be in association with the general loss of body fat. CONCLUSION: The control of body weight may be an important factor in the conservative management of patients with lumbosacral spinal lipomas.

Child↗
PubMed1998

Abnormal regulation of transforming growth factor-beta receptors on vascular smooth muscle cells from spontaneously hypertensive rats by angiotensin II.

The effects of angiotensin II (Ang II) on the expression and characteristics of transforming growth factor-beta (TGF-beta) receptors on vascular smooth muscle cells (VSMC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were investigated. TGF-beta-induced stimulation of DNA synthesis by VSMC from WKY rats was abolished with Ang II, whereas basal and TGF-beta-stimulated DNA synthesis by VSMC from SHR was increased with Ang II. Ang II stimulated DNA synthesis by VSMC from WKY rats in the presence but not in the absence of neutralizing antibody to TGF-beta1. Antibody to TGF-beta1 enhanced the stimulatory effect of Ang II on DNA synthesis by VSMC from SHR. Ang II increased the specific binding of TGF-beta to VSMC from WKY rats by increasing both the expression of the lower-affinity of TGF-beta receptors as well as the total number of TGF-beta binding sites. In contrast, VSMC from SHR showed a higher affinity and number of TGF-beta receptors in the absence of Ang II than did cells from WKY rats, and these parameters were not affected by Ang II. Ang II increased the expression of TGF-beta type I receptor mRNA in VSMC from WKY rats but had no effect of TGF-beta receptor type I or II mRNA in VSMC from SHR, which predominantly express the type II receptor. These results indicate that an increase in the expression of the TGF-beta type I receptor by Ang II may facilitate the ability of endogenous TGF-beta to counteract the stimulatory effect of Ang II on growth in VSMC from WKY rats, whereas endogenous TGF-beta induced by Ang II cannot counteract the growth-promoting action of Ang II in VSMC from SHR. The abnormal regulation of TGF-beta receptors by Ang II may be associated with the exaggerated growth of VSMC from SHR.

Angiotensin II↗
PubMed1998

[Inactivation and toxoiding of biologically-active components of Bordetella pertussis by tea catechins].

An ability of tea catechins known as agents for the disinfection to bacteria and viruses were tested on application for toxoiding biologically active components of Bordetella pertussis. The effects on the activities and antigenicity of filamentous hemagglutinin (FHA) and pertussis toxin (PT) were investigated. The activities of FHA and PT were inactivated by catechins at approximately 10(3) times lower dose (0.2 mM) compared with that of formalin. The activity of inactivated FHA was recovered by dialysis against Tris-HCl buffer, pH 8.0, containing glutathione or Tris-HCl buffer, pH 6.0. But the activity of inactivated PT was not recovered. Antigenicity of catechin-treated antigens were investigated by immunization to mice. The sera from mice immunized by catechin-treated FHA or PT were contained antibody against not only catechin-treated but also non-treated FHA or PT. These results suggest that antigenicity of FHA or PT was not destroyed by the treatment with catechin. We prepared pertussis-component vaccines by treatment of several catechins on the condition that FHA or PT activity was not recovered. Higher efficacy were found on the vaccines made by treatment of epicatechin, epicatechin gallate, or epigallocatechin than those by formalin. The vaccine prepared by using epigallocatechin gallate had significant efficacy as well as that by formalin treated one. From these results, it is suggested that tea leaf catechins were effective agents for toxoiding of vaccine components.

Animals↗
PubMed1998

Changes in intracellular Ca2+ mobilization and Ca2+ sensitization as mechanisms of action of physiological interventions and inotropic agents in intact myocardial cells.

Physiological and pharmacological interventions are used to regulate cardiac contractile functions via modulation of Ca2+ signaling. The relevant regulatory mechanisms have recently been assessed in detail by use of novel experimental procedures, which include simultaneous measurements of intracellular levels of Ca2+ ions and contractile force in intact myocardial preparations loaded with the intracellular Ca2+ indicator aequorin and fluorescent dyes, namely, fura-2, indo-1 and fluo-3. Association with or dissociation from intracellular Ca2+ transients of contractile activity is taken as evidence that reflects the primary mechanism of action of individual inotropic interventions. In addition, motility assays of actin-myosin interactions in vitro have made it possible to define the site of action of Ca2+ sensitizers as troponin C and the interaction of the troponin-tropomyosin complex with actin or the actin-myosin interface at crossbridges. Frank-Starling mechanism operates at the level of the binding of Ca2+ ions to troponin C and subsequent regulatory processes, while the force-frequency relationship is mainly ascribed to an alteration in the intracellular mobilization of Ca2+ ions. Cardiotonic agents can be classified as follows: 1) agents that act via a cyclic AMP-dependent or a cyclic AMP-independent mechanism; and 2) agents that facilitate the intracellular mobilization of Ca2+ ions or increase in myofibrillar sensitivity to Ca2+ ions. Regulatory mechanisms mediated via the phosphorylation of functional proteins induced by cyclic AMP, which is responsible for the actions of novel cardiotonic agents, beta 1-adrenoceptor partial agonist and selective inhibitors of phosphodiesterase (PDE) III, have currently been clarified in more detail. Ca2+ sensitizers are of extreme therapeutic interest because of their ability to increase myocardial contractility without an increase in activation energy; they are devoid of risks of arrhythmogenicity and myocardial cell death from intracellular Ca2+ overload; and they effectively reverse contractile dysfunction under pathophysiological situations, such as acidosis or myocardial stunning.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Susceptibility to Mycobacterium leprae of ALY (alymphoplasia) mice and IFN-gamma induction in the culture supernatant of spleen cells.

The aly/aly (alymphoplasia) mice from a mutation of a colony of the C57BL/6J mouse strain, which has a systemic absence of lymph nodes and Peyer's patches, are deficient in both T- and B-cell-mediated immune functions. We have undertaken a comparison of susceptibility to Mycobacterium leprae of ALY (aly/aly, aly/+) mice with C57BL/6J mice. The aly/aly mouse was found to have an excellent high susceptibility to M. leprae with no distinction between female and male. The aly/+ mouse also was more susceptible to M. leprae at an earlier stage than the C57BL/6J mouse. Therefore, we examined and compared the cytokine gene expression and gamma interferon (IFN-gamma) induction in the splenocytes of ALY mice. The expression of interleukin 4 (IL-4), IL-10 and IL-12 mRNA was weakly stimulated with ML-lysate in inoculated aly/aly mice but IL-2, IL-6, IGIF/IL-18 and IFN-gamma mRNA were not observed. None of the cytokine genes used appeared, except the mRNA for IL-1-alpha, when uninfected cultured spleen cells were stimulated with ML-lysate. Also, IFN-gamma production was not induced. However, the appearance of these cytokine genes was observed when stimulated with concanavalin A (ConA), and IFN-gamma production was also induced in the culture supernatant by aly/+ and even aly/aly mice stimulated with ConA. To examine the reason why IFN-gamma cannot be produced by splenocytes of ALY mice inoculated with M. leprae, we detected cytokine gene expression and IFN-gamma induction in the presence of recombinant murine IL-12 or IGIF/IL-18. IL-2 mRNA expression was detected in all of the mice tested in the presence of IL-12 but not in aly/aly mice under IGIF/IL-18, and iNOS mRNA expression was not observed in aly/aly mice under IL-12 or IGIF/IL-18. IL-4 and IL-10 mRNA were detected by aly/aly mice only by exposure to IGIF/IL-18. In culture, the supernatant with ML antigens of the aly/aly mice did not produce IFN-gamma in spite of the presence of IL-12 and IGIF/IL-18, while IFN-gamma was weakly induced in aly/+ mice stimulated with ML-lysate and in the presence of IGIF/IL-18. Nevertheless, IFN-gamma production was observed in splenocytes of the aly/aly mice stimulated with ConA and also with IGIF/IL-18 plus anti-CD3 antibody. Our results suggest that ALY mice might be showing a high susceptibility to M. leprae because of deficient priming for activation of T cells with the leprosy bacilli infection. Moreover, it is possible that the phagocytic activities of the macrophages of ALY mice are also impaired.

Animals↗
PubMed1998

[Snare injury in coronary artery bypass grafting on the beating heart: report of 2 cases].

From June to November 1997, 8 patients underwent coronary artery bypass grafting on the beating heart. The first 2 patients had snare injury. Postoperative angiography showed coronary stenosis distal to the LITA-LAD anastomosis in the first case and a pseudo-aneurysm at the septal branch of the LAD in the second case, most likely due to snaring maneuver with 3-0 prolene or 3-0 GORE-TEX suture with a sharp needle. Since then, we have been satisfactorily utilizing the RETRACT-O-TAPE (a silicone tape with blunt needle, QUEST Medical, Inc.) for coronary occlusion to avoid injury to the native vessels and their branches.

Angina Pectoris↗
PubMed1998

A novel cardiotonic agent SCH00013 acts as a Ca++ sensitizer with no chronotropic activity in mammalian cardiac muscle.

We investigated the inotropic effect of SCH00013 (4, 5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5, 6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one) on isolated dog and rabbit ventricular muscles and in indo-1 loaded rabbit ventricular cardiomyocytes. SCH00013 elicited a positive inotropic effect in a concentration-dependent manner (10(-6) to 10(-4) M) in both species in the presence of bupranolol. The positive inotropic effects of 10(-4) M SCH00013 on the dog and rabbit were 38% and 29% of the maximal response to isoproterenol. SCH00013 did not alter the rate of beating in isolated rabbit right atria. In indo-1 loaded rabbit ventricular cardiomyocytes, SCH00013 at 10(-4) M increased the systolic cell shortening by 52% above the base-line value in association with an insignificant increase in the systolic fluorescence ratio by 15% above the control. SCH00013 shifted the relationship between the Ca++ transients and cell shortening to the left as compared with that of elevation of [Ca++]o. In the dog and rabbit ventricular muscles, carbachol partially inhibited the positive inotropic effect of SCH00013. SCH00013 did not affect the positive inotropic effect of isoproterenol at 3 x 10(-6) M, but enhanced it at 3 x 10(-5) M. These results indicate that SCH00013 is a cardiotonic agent that primarily acts via an increase in myofibrillar Ca++ sensitivity with a moderate contribution of the cAMP-dependent mechanism at higher concentrations. SCH00013 has no chronotropic activity. The pharmacological profile of SCH00013 implies that the compound may be a promising cardiotonic agent for the treatment of congestive heart failure.

Animals↗
PubMed1997

Does nitric oxide contribute to the negative chronotropic and inotropic effects of endothelin-1 in the heart?

N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, was used to examine whether nitric oxide was involved in the negative chronotropic and inotropic effects of endothelin-1 in the presence of isoprenaline in mammalian heart. In isolated rabbit right atria, endothelin-1 elicited a negative chronotropic effect in the presence of isoprenaline, which was associated with a decrease in the isoprenaline-induced accumulation of cyclic AMP. On the other hand, in the dog ventricular trabeculae, the negative inotropic effect of endothelin-1 was not accompanied by a significant reduction in the isoprenaline-induced accumulation of cyclic AMP. N omega-nitro-L-arginine methyl ester affected neither the negative chronotropic effect nor the negative inotropic effect of endothelin-1. The effects of endothelin-1 on the isoprenaline-induced cyclic AMP accumulation were not influenced by N omega-nitro-L-arginine methyl ester either. These results indicate that the negative chronotropic and inotropic effects of endothelin-1 in the presence of isoprenaline in mammalian cardiac muscle do not involve the nitric oxide-mediated signaling pathway.

Adrenergic beta-Agonists↗
PubMed1997

Expression of cell division cycle 2 kinase transcription in chronically rejected cardiac allografts of nonhuman primates.

Accurate diagnosis and prevention of graft arteriosclerosis, known as chronic rejection, is critical to the success of cardiac transplantation, but often is difficult to attain. Expression of cell division cycle (cdc) 2 kinase, which plays a critical role in cell transition through the G2/M phase, is critical to the proliferation of vascular smooth muscle cells. To evaluate the usefulness of cdc2 kinase expression for pathophysiological analysis of chronic rejection, heterotopic cardiac transplantation was performed in Japanese monkeys (n = 7). Standard reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ RT-PCR were performed to evaluate the expression. In the coronary arteries of chronically rejected allografts, enhanced cdc2 kinase expression was observed in thickened intima and media, while none was expressed in native hearts. The cdc2 kinase was also expressed before the intimal thickening occurred. These results indicate that enhanced expression of cdc2 kinase is a sensitive indicator for chronic cardiac rejection; targeting cdc2 kinase may be a viable gene therapy for prevention of this vasculopathy.

Animals↗