[Effects of vasoactive peptides on the development of restenosis].
OBJECTIVE
To investigate the effects of several vasoactive peptides on the development of restenosis.


METHODS
The model of balloon angioplasty to the rat aorta was prepared and used to study the changes of endothelin (ET), angiotensin II (A II), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in the plasma and aorta tissues, with radioimmuno-assay. (3)H-TdR incorporation and intima/media ratio of aortic tissue were measured after angioplasty. In cultured vascular smooth muscle cells, effects of these peptides on the proliferation of VSMC were evaluated with (3)H-TdR incorporation. Effects of these peptides on the expression of hypertension-related gene (HRG-1) in aorta tissue and cultured VSMC from SHR and WKY rats were studied by semi-quantitative RT-PCR.


RESULTS
After angioplasty, the levels of ET and A II in the plasma and/or aorta tissue were significantly increased, with VSMC proliferation. On day 10 after angioplasty, the levels of ET in the plasma and tissue were increased by 69% and 124% respectively, compared with the that in the control group (P < 0.01); and the levels of aortic A II were increased by 80% (P < 0.01). Antiserum against ET and angiotensin converting enzyme (ACE) inhibitors could obviously inhibit the proliferation of VSMC and neointima formation. Compared with the sham group on day 3 after angioplasty, the CGRP levels in plasma and aorta tissue were increased by 64% and 89% respectively (P < 0.01); the Adm levels in the plasma and aorta tissue were increased by 129% and 102% respectively (P < 0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury with the inhibitory rate of 66% and 79%, respectively, (P < 0.01). ET and A II attenuated the expression of HRG-1 in the aorta, thus activating mitogen activated protein kinase (MAPK). CGRP and Adm potentiated the expression of HRG-1, thus inhibiting the activity of MAPK.


CONCLUSIONS
ET and A II stimulate the proliferation of injured intima, and CGRP and Adm have an anti-hyperplasia effects after angioplasty. That these peptides are suggested to be involved in the regulation of proliferation of VSMC and to affect the developing of vascular restenosis, by means of regulating the expression of HRG-1 and MAPK activities.
Liu
N
N
Institute of Cardiovascular Research, First Hospital of Peking University, Beijing 100034, China.
Chen
G
G
Wang
X
X
D053607:Adrenomedullin; D000804:Angiotensin II / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D023903:Coronary Restenosis / Q000209:etiology* / Q000503:physiopathology; D016232:Endothelins / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017539:Tunica Intima / Q000187:drug effects* / Q000503:physiopathology
D016232:Endothelins; D010455:Peptides; D000804:Angiotensin II; D053607:Adrenomedullin; D020928:Mitogen-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide