title: Disruption of elastic lamellae in the aorta by D-penicillamine and its effect on vaso-regulation in rats.
abstract: 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.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Muto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Masaru
authors.initials: M
authors.lastname: Bamba
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirota
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D062186:Arterial Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003895:Desmosine / Q000378:metabolism; D004547:Elastic Tissue / Q000187:drug effects* / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects*; D004549:Elastin / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D007524:Isodesmosine / Q000378:metabolism; D008297:Male; D010396:Penicillamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D002614:Chelating Agents; D003895:Desmosine; C015484:pyridinoline; D004549:Elastin; D007524:Isodesmosine; D010396:Penicillamine