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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2009-2-24
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pubmed:abstractText |
Calcitonin gene-related peptide (CGRP)-alpha is expressed in heart ventricles in sensory nerves and cardiomyocytes. It modifies inotropism and induces ischaemic preconditioning. This study investigates the effect of CGRP-alpha on the contractile responsiveness of isolated adult ventricular rat cardiomyocytes and the effect of chronic hypertension on this interaction. Cardiomyocytes were isolated and paced at 0.5-2.0 Hz. Cell shortening was recorded via a line camera with a reading frame of 500 Hz. CGRP-alpha exerted a dual effect on cardiomyocytes with a positive contractile effect at 10nM and a negative contractile effect at 10 pM. CGRP-alpha(8-37), a calcitonin receptor-like receptor (CRLR) antagonist, attenuated the positive contractile effect. H89, a protein kinase A antagonist, converted the positive contractile effect into a negative contractile effect. The negative contractile effect was converted again back to a positive contractile effect in the presence of l-nitro arginine. In cardiomyocytes isolated from spontaneously hypertensive rats (SHR) the mRNA expression of CRLR and the receptor-associated modifier protein (RAMP)-2 were lower. However, on the protein level CLRL was up-regulated, RAMP2 expression remained unchanged, and eNOS expression was down-regulated in these cells. These cells responded with a pure positive contractile response. In Langendorff preparations, CGRP-alpha slightly reduced the rate pressure product in hearts from normotensive rats but it caused an increase in hearts from SHR. In conclusion, it is shown that CGRP-alpha exerts dual effects on cardiomyocytes favouring the negative contractile effect at very low concentrations. This effect is compensated in chronic pressure-overloaded hearts and converted into a positive inotropism.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Gene-Related Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Receptor-Like Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcrl protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ramp2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activity-Modifying...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activity-Modifying Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitonin,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/calcitonin gene-related peptide...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1618-1298
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
227-41
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19128857-Animals,
pubmed-meshheading:19128857-Blood Pressure,
pubmed-meshheading:19128857-Calcitonin Gene-Related Peptide,
pubmed-meshheading:19128857-Calcitonin Receptor-Like Protein,
pubmed-meshheading:19128857-Calcium,
pubmed-meshheading:19128857-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:19128857-Heart Ventricles,
pubmed-meshheading:19128857-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19128857-Isoquinolines,
pubmed-meshheading:19128857-Membrane Proteins,
pubmed-meshheading:19128857-Myocardial Contraction,
pubmed-meshheading:19128857-Myocytes, Cardiac,
pubmed-meshheading:19128857-Nitric Oxide Synthase Type III,
pubmed-meshheading:19128857-Peptide Fragments,
pubmed-meshheading:19128857-Protein Kinase Inhibitors,
pubmed-meshheading:19128857-Rats,
pubmed-meshheading:19128857-Rats, Inbred SHR,
pubmed-meshheading:19128857-Rats, Wistar,
pubmed-meshheading:19128857-Receptor Activity-Modifying Protein 2,
pubmed-meshheading:19128857-Receptor Activity-Modifying Proteins,
pubmed-meshheading:19128857-Receptors, Calcitonin,
pubmed-meshheading:19128857-Sulfonamides,
pubmed-meshheading:19128857-Ventricular Function
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pubmed:year |
2009
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pubmed:articleTitle |
CGRP-alpha responsiveness of adult rat ventricular cardiomyocytes from normotensive and spontaneously hypertensive rats.
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pubmed:affiliation |
Physiologisches Institut, Justus-Liebig-Universität, Aulweg 129, D-35392 Giessen, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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