Prevention by calcitonin of the pathological modifications of the rabbit arterial wall induced by immunization with elastin peptides: effect on vascular smooth muscle permeability to ions.
Immunization of rabbits with elastin peptides prepared from purified bovine ligamentum nuchae elastin produces calcified arteriosclerotic lesions and fragmentation of elastic lamellae. Simultaneous administration of porcine calcitonin largely prevents the development of lesions. Experiments were carried out to clarify the mechanisms involved in the development of lesions as well as those involved in the preventive effect of calcitonin. Control experiments were carried out using bovine serum albumin (BSA) as antigen. Circulating antibodies and soluble immune complexes increased steadily in the sera of animals immunized with elastin peptides or BSA. The cellular immune reaction was weak as assessed by [3H]thymidine incorporation into lymphocytes in the presence of antigen or phytohemagglutinin. Arterial lesions appeared only in the animals immunized with elastin peptides, not in those immunized with BSA. Ion flux measurements were also carried out on strips of aorta obtained from immunized and control animals. Immunization with elastin peptides significantly increased the ouabain-insensitive 22Na+ efflux, the 86Rb efflux (indicator of K+ efflux), and the 45Ca2+ influx. Simultaneous calcitonin administration prevented the increase in Ca2+ influx but did enhance passive permeability to Na+ and K+ as well as the sodium pump. When calcitonin was administered without immunization, it decreased arterial smooth muscle permeability to Na+ and K+ and also decreased the basal Ca2+ influx. It is concluded that the pathological modifications of the arterial wall triggered by immunization with elastin peptides is at least partly mediated by the effect of antielastin antibodies and immune complexes on the ion permeability of arterial smooth muscle. Prevention of the increased Ca2+ influx by calcitonin is probably a key effect in the prevention of the development of lesions. The fact that calcitonin alone can modify the ion permeability of arterial smooth muscle suggests that this hormone may play a role in the regulation of vascular homeostasis.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002116:Calcitonin / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004549:Elastin / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000276:immunology
D000936:Antigen-Antibody Complex; D007473:Ion Channels; D012710:Serum Albumin, Bovine; D002116:Calcitonin; D004549:Elastin