Disruption of elastic lamellae in the aorta by D-penicillamine and its effect on vaso-regulation in rats

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  • Muto Takafumi
    Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Miyajima Atsushi
    Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Bamba Masaru
    Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Hirota Takashi
    Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science

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We assessed the effects of D-penicillamine (D-PA) on cross-linkages in elastin and vaso-regulatory function in rats. After administration of D-PA at a dose of 100 mg/kg/day for 7 weeks to adult and young rats, the thoracic aortas were isolated. The elastic lamellae in the aorta were disrupted histopathologically in all the treated groups. The content of cross-linkages in elastin, i.e. desmosine and isodesmosine, which gives elasticity to the aortic wall, was significantly reduced in the D-PA treated groups versus the control groups. On the other hand, the content of pyridinoline as a marker of insoluble collagen was significantly reduced in the D-PA treated groups, even though the total collagen content was not changed. In addition, after 7 weeks of treatment with D-PA, the change between systolic blood pressure before and after sympathetic stimulation (Δ-SBP) by L-epinephrine was about 2.5-fold larger than that in the control group. Similar results were obtained using angiotensin II or ouabain instead of L-epinephrine. These findings demonstrated that D-PA disrupted elastic lamellae of the rat aorta by reduction of the cross-linkages in elastin and collagen, which caused dysfunction of vaso-regulation. Also, they suggested the possibility that long-term treatment with D-PA in patients could cause a decrease in vaso-regulatory function and could increase the risk of cardiovascular events.

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