Are you Toshihiko Fukuda?

Claim your profile

Publications (4)8.96 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.
    PLoS ONE 02/2014; 9(2):e88975. DOI:10.1371/journal.pone.0088975 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Trp-His is the only vasoactive di-peptide known to regulate intracellular Ca(2+) ([Ca(2+)]i) and prevent the onset of atherosclerosis in mice. In this study, we showed that Trp-His reduced the [Ca(2+)]i elevation in phospholipase C-activated vascular smooth muscle cells (VSMCs), while a mixture of the corresponding constituent amino acids did not show significant reduction. Furthermore, Trp-His suppressed calmodulin-dependent kinase II (CaMK II) activity in angiotensin II-stimulated VSMCs, resulting in the inhibition of phosphorylation of voltage-dependent L-type Ca(2+) channels (VDCC). Therefore, Trp-His potentially regulates the VDCC phosphorylation cascade through Ca(2+)-CaM/CaMK II.
    04/2012; 2:83-8. DOI:10.1016/j.fob.2012.04.005
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adenine had a concentration-dependent relaxation action on the phenylephrine-contracted aorta ring, with an EC(50) value of 0.40±0.12 mM. This effect was also observed in the endothelium-denuded aorta. Among the adenine analogues, N-methyladenine and benzimidazole still evoked an apparent relaxation effect, while 1-, 3- or 7-methyladenine and imidazole were no longer vasodilators. These findings demonstrate that the imino group from the uncharged imidazolium moiety in adenine played a key role in the relaxation of the contracted aorta.
    Bioscience Biotechnology and Biochemistry 04/2012; 76(4):828-30. DOI:10.1271/bbb.110806 · 1.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: A series of our studies provided evidences that vasorelaxant di-peptide, Trp-His (WH), exhibits an anti-atherogenic effect and partly inhibited a Ca2+ influx like dihydropyridine type-voltage-dependent L-type Ca2+ channel (VDCC) blocker. However, further inhibitory potential(s) in intracellular Ca2+-signaling pathways are still unclear. In this study, we attempted to elucidate alternative vasoprotective mechanism of WH in the intracellular Ca2+-signaling pathways. Methods: Vascular smooth muscle cells (VSMCs) from 8-wk-old WKY rats were used to determine [Ca2+]i. Measurement of [Ca2+]i was performed using Fura-2, a Ca2+-specific probe, monitored at of dual-excited fluorescence at 340/380 nm (Emission: 500 nm). Activities of Protein Kinase C (PKC)s and calmodulin-dependent kinase II (CaMK II) were measured by ELISA and phosphorylation of VDCC was evaluated by Western blot. Results: WH (300 [mu]M, not its corresponding amino acids) strongly suppressed the increase in [Ca2+]i in angiotensin II (Ang II)-stimulated VSMCs ([DELTA][Ca2+]i: Control; 620.0 nM, WH; 53.3 nM, P < 0.01). WH did not attenuate Ang II-induced Ca2+ release from the endoplasmic/sarcoplasmic reticulum, while significantly inhibited phospholipase C (PLC)-activated [Ca2+]i elevation in m-3M3FBS (a PLC activator)-stimulated VSMCs ([DELTA][Ca2+]i: Control; 221.8 nM, WH; 63.2 nM, P < 0.01). In PLC-related signaling pathways, involving the facilitation of VDCC by Ca2+-related kinases such as CaMK II, WH inhibited CaMK II activity (P < 0.05). Furthermore, WH suppressed the phosphorylation of VDCC (P < 0.05). Conclusions: In AngII-induced vasoconstriction signaling pathway, we demonstrated for the first time that WH regulates [Ca2+]i in VSMCs through the suppression of PLC/CaMK II/VDCC phosphorylation pathway.
    Journal of Hypertension 01/2012; 30:e273-e274. DOI:10.1097/01.hjh.0000420867.10354.23 · 4.22 Impact Factor