Biomedical subjects

T Iesaki

Publications and source records attributed to T Iesaki.

4 recordsLinked to original sources

PubMed1996

Decrease in Ca2+ sensitivity as a mechanism of hydrogen peroxide-induced relaxation of rabbit aorta.

OBJECTIVE: In vascular strips, hydrogen peroxide (H2O2) relaxes alpha 1-adrenergic agonist-induced but not high-K(+)-induced contractions. The aim of this study was to explore H2O2-induced changes in [Ca2+]i of vascular smooth muscle and to elucidate the mechanisms of action of H2O2. METHODS: Isolated rabbit aortic strips were isometrically contracted with high-K+ (64.7 mM) or phenylephrine (PE, 0.3 microM). The effects of 300 microM H2O2 on [Ca2+]i of endothelium-denuded vascular smooth muscle and tension were determined simultaneously by the fura-2 method. Changes in [Ca2+]i were expressed as percentages of high-K(+)-induced values measured at the beginning of the experiments. In another series of experiments, the relaxant effect of 300 microM H2O2 was examined in high-K+ (20 mM)-induced contraction in the presence of the protein kinase C activator, phorbol 12,13-dibutyrate (PDBu). RESULTS: Hydrogen peroxide caused a reversible rise in [Ca2+]i of vascular smooth muscle under both resting conditions and in the precontracted state. During high-K(+)-induced contraction, H2O2 further increased [Ca2+]i by 26.6(s.e.m. 1.7)% accompanied by a small increase in tension of 6.5(1.9)% of high-K(+)-induced tension. By contrast, during PE-induced contraction, although H2O2 caused a comparable additional increase in [Ca2+]i (26.4(4.7)%), muscle tension fell by 28.9(2.2)% of the steady-state PE-induced tension. Hydrogen peroxide had a relaxant effect on augmented high-K(+)-induced contraction in which Ca2+ sensitivity of the contractile apparatus was elevated by PDBu. CONCLUSIONS: In spite of its effect of increasing [Ca2+]i of vascular smooth muscle, hydrogen peroxide causes relaxation of endothelium-denuded, PE-precontracted rabbit aorta. The mechanism is probably through suppression of agonist-induced augmentation of Ca2+ sensitivity of the contractile apparatus.

Animals↗

PubMed1994

Inhibition of vasoactive amine induced contractions of vascular smooth muscle by hydrogen peroxide in rabbit aorta.

OBJECTIVE: The aims were to investigate the effects of H2O2 on arterial contractions induced by vasoactive amine agonists and a high concentration of potassium ions (high K+) in vitro and to explore the possible underlying mechanism(s) involved. METHODS: Isometric tension of rabbit isolated aortic strips was measured and the effects of pretreatment with H2O2 on contractions induced by phenylephrine and high K+ were compared. The effects of H2O2 on precontracted strips were determined in the presence and absence of the aortic endothelium and compared with those of acetylcholine. RESULTS: The tension developed in response to an agonist was expressed as a percentage of the contraction induced by high K+ (64.7 mM) superfusion. Pretreatment with 300 microM H2O2 reduced the mean phenylephrine (0.3 microM) induced contraction from 96.2(SEM 1.4) to 61.8(2.8)%; the effect was stable and reversed by washing out the H2O2. Hydrogen peroxide relaxed phenylphrine precontracted strips with and without endothelium but it showed no relaxant effect when the strips were precontracted by high K+, whereas acetylcholine (1 microM) induced transient relaxation of high K+ precontracted strips by 27.8(2.9)%. The relaxant effect of H2O2 was not affected by pretreatment with indomethacin (a cyclo-oxygenase inhibitor), desferrioxamine (a hydroxyl radical scavenger), or diphenylphenylenediamine (a lipophilic antioxidant). CONCLUSIONS: H2O2 inhibits vasoactive amine induced contractions of the vascular smooth muscle of rabbit aorta in vitro without affecting voltage dependent Ca2+ influx or contractile machinery. The mechanism responsible for its inhibitory effects may be related to impairments of the cellular signalling reactions initiated by the agonists.

Acetylcholine↗

PubMed1994

[A 46-year-old man with cardiac failure and statues epileptics].

We report a 46-year-old man with bacterial endocarditis and cardiac failure, who developed status epileptics. The patient was apparently well until July of 1991 when there was a gradual onset of fever and general fatigue. He was hospitalized to the cardiology service of our hospital where diagnosis of bacterial endocarditis and aortic insufficiency was made. On October 9, 1991, he suddenly developed cardiogenic shock, and emergency replacement of the aortic valve was made; at the operation, the main trunk of the left coronary artery showed embolic occlusion, and the myocardial movement was markedly diminished; serum creatine kinase was 3.150 IU/l. His cardiac failure did not resolve, and renal failure developed in December 1991, for which peritoneal dialysis was necessary. On February 2, 1992, he suddenly developed a clonic seizure which started from his face with a transient post-ictal left hemiparesis; a cranial CT scan was unremarkable. He was treated with phenytoin and glycerol, however, he developed status epileptics on February 3; he developed cardiac arrest after the injection of phenytoin 750 mg. He was resuscitated, however, his status did not resolve. Neurological consultation was asked on February 4. On physical examination, his blood pressure was 80/40 mmHg heart rate 77/min and regular, and body temperature 39.1 degrees C. The palpebral conjunctiva were slightly anemic, however, the bulbar conjunctiva were not icteric. No cervical adenopathy was noted. Glade II systolic murmur was heard in the apex; the lungs were clear. The abdomen was flat and soft without organomegaly. No edema was present in the legs. On neurologic examination, he was comatose without response to painful stimuli. He repeatedly had convulsion lasting for 30 seconds every 2 to 3 minutes; his convulsions started with the conjugate deviation of the eyes to the left followed by turning of the head toward left, and then clonic convulsions started in this left upper limb extending to other extremities. The optic fundi were unable to visualize because of corneal clouding; light reflex was sluggish on the right side; no oculocephalic response was elicited; corneal reflex was also lost bilaterally. Extremities were hypotonic, and no automatic movement was seen. The triceps brachii reflex was diminished, but all the other deep reflexes were lost; no plantar response was elicited. Meningeal sign was absent. He was treated with intravenous diazepam; the interval of convulsions prolonged, however, blood pressure dropped to 40 to 40 mmHg. On February 4, intravenous thiopental anesthesia was instituted, and assisted respiration was started.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

PubMed1990

[Postgastrectomy megaloblastic anemia--possible participation of anti-intrinsic factor antibody in its pathogenesis--report of a case].

A case of 78-year old man with megaloblastic anemia occurring 20 years after partial gastrectomy is reported. Since about 2 years earlier he had an episode of convulsion, and he had been on anti-convulsants (diphenylhydantion, phenobarbital) until admission. Physical examination revealed a pale lean man with polyneuropathy and mental impairment. Laboratory findings revealed WBC 3100/microliters, RBC 187 X 10(4)/microliters, HB 7.9 g/dl, MCV 124.4 microns3, MCH 42.7 micrograms, platelet counts 15.7 X 10(4)/microliters, serum vitamin B12 (VB12) 380 pg/ml, and serum folic acid 5.1 ng/ml. Serum autoantibodies to intrinsic factor (IF) and parietal cells were positive. Bone marrow examination revealed erythroid hyperplasia and megaloblastic changes. Schilling test revealed impaired absorption of VB12 with or without IF, but X-ray study of the small bowels was unremarkable. Treatment with intramuscular cyanocobalamin resulted in a rapid clinical improvement. A repeat Schilling test after 4 months of therapy showed a normal VB12 absorption in the presence of IF. These findings suggest that VB12 malabsorption of the 1st Schilling test was due to intestinal dysfunction caused by the VB12 deficiency state itself, and the improvement of VB12 absorption with IF after therapy suggests a pathogenesis similar to pernicious anemia in this patient.

Aged↗