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 and METHODS: : The present study observed the change of L-arginine (L-Arg)/Nitric oxide (NO) pathway in ergthrocytes in hypertension with insulin resistance rat induced by fructose and the effect of taurine on L-Arg/NO pathway. RESULTS: Drinking 4% fructose, while inducing blood pressure, glucose and plasma insulin contents increase, obviously decreased the maximal velocity of L-Arg transport about 31% and 37% (P
ABSTRACT
AIM: To investigate the changes of L-arginine/nitric oxide(L-Arg/NO) pathway and the characteristics of L-Arg transport in erythrocytes (RBC) in patients with essential hypertension(EH). METHODS: 12 EH patients were studied with 10 normotensive people as control. The nitric oxide (NO) production was assayed by measuring the nitrite in medium using Greiss reaction. NO synthase activity was measured according to the method described by Ghigo. In order to achieve zero-trans condition, erythrocytes were incubated at 37℃ for 3 h and then L- Arg transport of RBC were determined by measuring the influx of radiolabelled L-arginine by Deliconstantins described method.RESULTS: In EH patients, NO production was lower than that in control (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
ABSTRACT
Cardio-protective action of synthetic peptide 6A, fibrinogen degradation segment, was observed on the myocardial injury model produced by subcutaneous injection of iso-proterenol (30 mg?kg-1-d-1) into rat. Treatment with peptide 6A (50 ?mol?kg-1? d-1,iv) significantly ameliorated isoproterenol-induced myocardial lesion, inhibited release of myocardial creatine phosphokinase, ?-hydroxybutyratedehydrogenase, lactate dehydrogenase and gluta-mate-oxaloacetate transaminase, lowered plasma fibrinogen content,and markedly prevented myocardial calcium accumulation. The results suggest that peptide 6A could have potential significance for clinical therapy of ischemia heart diseases.
ABSTRACT
AIM: To study the influence of PD098059 on the rat platelet aggregation rate and the phosphorylation of ERK1/2 induced by the different agonists, and to observe the effects of phosphorylation of ERK1/2 on the platelet aggregation. METHODS: The maximal aggregation rate (MAR) was measured by nephelometry. The inhibitory rate of PD098059 and the appearing time of MAR were also observed. ERK1/2 phosphorylation was detected by Western blot. RESULTS: The phosphorylation of ERK1/2 was detected during aggregation induced by thrombin and ADP. PD098059 inhibited the MAR and phosphorylation of ERK1/2. Effects of PD098059 were different on the aggregation induced by thrombin and ADP. CONCLUSIONS: The phosphorylation of ERK1/2 is one of the cellular signal transduction mechanisms of platelets aggregation. Phosphorylation of ERK1/2 plays different roles during the platelet aggregation induced by thrombin and ADP. [