C-type natriuretic peptide inhibits upregulation of alpha1-adrenoceptor and inositol 1,4,5-trisphosphate receptor in rat vascular smooth muscle after vascular endothelial injury.

OBJECTIVE: In a model of balloon injury of rat aortic endothelium, the effects of C-type natriuretic peptide (CNP) on alpha1-adrenoreceptor and inositol 1,4,5-triphosphate (IP3) receptor were studied. METHODS: Aortic injuries were produced by vascular endothelium-denudation. Alpha1-adrenoreceptor in smooth muscle sarcolemma and IP3 receptor in smooth muscle sarcoplasmic reticulum in the rat aorta were assayed by radioactive analysis method. RESULTS: It was found that neointima was formed and the contents of DNA, collagen and elastin of each intima-media were sigificantly increased in 7 days and 21 days after balloon injury of rat aorta. Alpha1-adrenoreceptor in smooth muscle sarcolemma and IF3 receptor in sarcoplasmic reticulum were also upregulated. Results also showed that the administration of CNP i.p. significantly decreased the contents of DNA, collagen and elastin of each intima-media, and inhibited the up-regulation of alpha1-adrenoreceptor and IP3 receptor. CONCLUSION: The inhibition of the up-regulation of alpha1-adrenoreceptor and IP3 receptor by CNP might be one of the mechanisms of its suppressive action on intimal proliferation.

Role of endogenous carbon monoxide in neointimal formation induced by balloon-injury in rat aorta.

OBJECTIVE: The present study investigated the role of endogenous carbon monoxide (CO) in the pathogenesis of neointimal formation induced by balloon injury in rat. METHOD: Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter. DNA, collagen and elastin contents of each intima-media were estimated; and heme oxygenase (HO) activity and CO production in vascular smooth muscle cell (VSMC) were measured after administration of HO inhibitor. RESULT: Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury, and at the same time HO activity and CO production in VSMC were markedly increased. Administration of HO inhibitor, zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG), could effectively inhibit HO activity and CO production, significantly enhance neointimal formation (aortic intima/media ratio were 21.4+/-1.8% vs 17.6+/-2.0%, P<0.05 on day 7; and 30.5+/-2.4% vs 23.0+/-2.2%, P<0.01 on day 21, respectively, compared with balloon alone group). CONCLUSION: We concluded that 1) inhibition of CO production may enhance neointimal formation induced by endothelial denudation, implying endogenous CO play an protective role in response to vascular injury, and 2) induction of HO activity may be applied clinically for preventing restenosis after angioplasty.