Abstract:
OBJECTIVE:While natriuretic peptides can inhibit growth of vascular muscle cells (VSMC), controversy exists as to whether this effect is mediated via the guanylate cyclase-coupled receptors, NPR-A and NPR-B, or the clearance receptor, NPR-C. The original aim of this study was to examine the mechanism by which the NPR-C receptor regulates growth. METHODS:Rat VSMC were characterized with regard to natriuretic peptide receptor expression by RT/PCR and radioligand binding studies. The effect on growth following addition of the peptides and the ligands for NPR-C was measured by [3H]thymidine incorporation. Cyclic guanosine monophosphate (cGMP) levels were determined by radioimmunoassay and mitogen activating protein kinase activity was based on the phosphorylation of myelin basic protein. RESULTS:In rat VSMC, passages 4-12, both atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) dose-dependently inhibited serum and PDGF-induced VSMC growth. In contrast, NPR-C specific ligands alone had no effect on cell growth but enhanced growth inhibition when co-administered with ANP and CNP. ANP and CNP also decreased PDGF-BB-stimulated MAP kinase activity. Once again, NPR-C specific ligands alone had no effect but enhanced the effects of ANP. Furthermore, a cGMP specific phosphodiesterase inhibitor dose-dependently inhibited VSMC growth and markedly enhanced natriuretic-peptide-induced inhibition at low peptide concentrations. To examine a potential mechanism for the controversy concerning the NPR-C, we investigated the autocrine expression of ANP and CNP by VSMC and found that mRNA encoding both peptides could be detected by RT/PCR. CONCLUSION:Our findings indicate that the guanyl-cyclase-linked receptors mediate the antiproliferative actions of the natriuretic peptides on vascular smooth muscle cell growth. Moreover, we hypothesize that the apparent inhibition of growth by NPR-C specific ligands reported by others may be due to stabilization of natriuretic peptides produced by the cultured VSMC and subsequent action of these peptides at guanyl-cyclase-linked receptors.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Hutchinson HG,Trindade PT,Cunanan DB,Wu CF,Pratt REdoi
10.1016/s0008-6363(97)00086-2subject
Has Abstractpub_date
1997-07-01 00:00:00pages
158-67issue
1eissn
0008-6363issn
1755-3245pii
S0008636397000862journal_volume
35pub_type
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
pub_type: 杂志文章
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journal_title:Cardiovascular research
pub_type: 杂志文章
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doi:10.1016/s0008-6363(02)00601-6
更新日期:2002-12-01 00:00:00
abstract::Methodology has been developed for utilising ultrasonic crystals in closed chest cats to measure alterations in regional left ventricular function. The technique is a modification of one previously utilised to monitor regional left ventricular length and thickness changes in closed chest dogs. The ultrasonic crystals ...
journal_title:Cardiovascular research
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doi:10.1093/cvr/12.6.387
更新日期:1978-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-11-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.03.011
更新日期:2005-07-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2018-07-15 00:00:00
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journal_title:Cardiovascular research
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更新日期:2004-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.04.018
更新日期:2007-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu152
更新日期:2014-09-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp116
更新日期:2009-08-01 00:00:00
abstract::Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.10.721
更新日期:1986-10-01 00:00:00
abstract:OBJECTIVE:The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydrox...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.494
更新日期:1993-03-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2015-06-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00044-4
更新日期:2000-05-01 00:00:00
abstract::It has long been known that gap junctions are required for the propagation of electrical impulse in the heart. A good deal later, the connexins (Cxs), which are probably exclusive components of the junctional channels that constitute the gap junctions, were identified. More recently, the in vivo functions of cardiac C...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.02.010
更新日期:2004-05-01 00:00:00