ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty.</p><p><b>METHODS</b>In rat aortic artery restenosis model produced by denudation of aortic endothelia, we observed changes of endothelin (ET), angiotensin II (AII), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in plasma and aorta with radioimmunoassay and expression of hypertension-related gene (HRG-1) with semi-quantitative RT-PCR, and studied the effects of these peptides on intimal hyperplasia, intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore, in cultured cells, we studied the effects of these peptides on vascular smooth muscle cell (VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with 3H-TdR incorporation and RT-PCR respectively.</p><p><b>RESULTS</b>After angioplasty, the levels of ET and AII in plasma and aorta significantly increased, accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty, the levels of ET in plasma and aorta increased by 69% and 124% respectively, compared with sham group (P < 0.01); and the level of aortic AII increased by 80% (P < 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme (ACE) could significantly 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 increased by 64% and 89% respectively (P < 0.01) and the Adm levels in plasma and tissue 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 (by 66% and 79% respectively, P < 0.01). In addition, ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase (MAPK) activity, while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK.</p><p><b>CONCLUSIONS</b>ET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.</p>
Subject(s)
Animals , Male , Rats , Adrenomedullin , Angioplasty, Balloon , Angiotensin II , Pharmacology , Therapeutic Uses , Aorta, Thoracic , Cell Biology , Metabolism , Calcitonin Gene-Related Peptide , Pharmacology , Therapeutic Uses , Cell Division , Cells, Cultured , Coronary Restenosis , Metabolism , Endothelin-1 , Pharmacology , Therapeutic Uses , Mitogen-Activated Protein Kinases , Metabolism , Muscle, Smooth, Vascular , Cell Biology , Peptides , Pharmacology , Therapeutic Uses , Rats, Inbred SHR , Rats, Inbred WKY , Rats, Wistar , Vasodilator Agents , Pharmacology , Therapeutic UsesABSTRACT
AIM: To investigate the effect of endothelin (ET), angiotensin II (AngII) and homocysteine (Hcy) on C-type natriuretic peptide (CNP) synthesis and release. METHODS: Human endothelial cell was cultured; CNP was measured by radioimmunoassay method. RESULTS: ET and AngII could augment CNP synthesis in human endothelial cells. Compared with control group, 10-9,10-8,10-7 mol/L ET and Ang II increased CNP content of endothelial cells by 1%(P＞0.05), 49%(P＜0.05),117%(P＜0.01) and 137% (P＜0.01),165%(P＜0.01),201%(P＜0.01),respectively. A great dose of ET and Ang II also stimulated CNP release from cultured human endothelial cells. Hcy had no effect on CNP synthesis, but 10-9，10-8,10-7 mol/L Hcy enhanced CNP release from cultured human endothelial cells by 17%(P＞0.05),84%(P＜0.01) and 555%(P＜0.01), respectively. CONCLUSION: ET, AngII and Hcy might be involved in the synthesis and release of human endothelial cell CNP.
ABSTRACT
AIM: To study the role and regulation of calcineurin(CaN) in angiotensin II(AngⅡ)-stimulated cardiacmyocyte hypertrophy of rats. METHODS: Using AngⅡ to induce the cultured cardiac myocyte hypertrophy of rats, and investigating the effect of CaN inhibitor on [ 3H]-leucine incorporation of AngⅡ-stimulated cardiomyocytes and the regulation of various factors on CaN activity in cardiomyocytes.RESULTS: AngⅡ can stimulate the CaN activity in cultured neonatal rat cardiomyocytes in a dose- and time-dependent manner. In cardiac myocytes incubated with 10, 100, 1000 nmol?L -1 of AngⅡ for 12h, the CaN activities increased respectively by 13%,57%( P
ABSTRACT
AIM: To observe the changes in mitogen-activated protein kinases (MAPKs) activity and gene expression of c-fos after coronary artery balloon injury in swine. METHODS: Six of the seventeen Chinese swine were as control group, and the others underwent coronary angioplasty to LAD or CLx. The animals were sacrificed at three and thirty days following the procedure. The cross-sections were stained hematoxylin-eosin, strichrome, and Verhoef-van Giesen after the target segments were dissected free from the hearts, and the morphologic characteristics were investigated by computer-assistant analysis system. The target segments were also processed to examine the gene expression of c-fos by reverse transcription-polymerase chain reaction (RT-PCR) and to measure the activity of MAPKs by biochemistry. RESULTS: MAPKs activity and gene expression of c-fos in the dilated segments were significantly higher than that of normal segments three days after coronary balloon injury (51.5%, P
ABSTRACT
AIM and METHODS: In a model of balloon injury of rat aorta, the dynamic changes of C-type natriuretic peptide (CNP) in plasma and aortic tissues and the effect of exogenous CNP on intima/media (I/M) ratios were studied. RESULTS:CNP levels in plasma were significantly increased by 80.7% (P