Linked Life Data

8882168

Source:http://linkedlifedata.com/resource/pubmed/id/8882168

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-12-13
pubmed:abstractText
Relaxin, a reproductive hormone of the insulin-like growth factor family, increases heart rate in experimental animals but its other actions on cardiac function and cellular mechanisms responsible for the positive chronotrophic effect remain unknown. We have studied the actions of human recombinant gene-2 relaxin on the release of atrial natriuretic peptide (ANP) and cardiac function (heart rate, contractile force, perfusion pressure) as well as the underlying signal transduction mechanisms by using the isolated perfused spontaneously beating rat heart preparation. The administration of relaxin into the perfusion fluid at concentrations of 1.5, 3 or 10 nM for 30 min caused a dose-dependent sustained increase in heart rate, while contractile force and perfusion pressure remained unchanged. In addition, infusion of relaxin at a concentration of 10 nM into the perfusate produced a gradual 1.5-fold increase in immunoreactive ANP (IR-ANP) secretion (from 456 +/- 76 to 701 +/- 124 pg/ml, F = 4.5, P < 0.001). The ANP secretory and chronotrophic effects of relaxin appear to involve the activation of protein kinase C, since administration of a protein kinase C inhibitor staurosporine at a concentration of 30 nM completely blocked the effect of relaxin (10 nM) on IR-ANP secretion (P < 0.001) and heart rate (P < 0.001). A cAMP-dependent protein kinase inhibitor, H-89 (100 nM), also substantially reduced the ANP secretory effect of relaxin and attenuated the increase in heart rate during the sustained phase of the relaxin infusion (P < 0.001). KN-62 (3 microM), a Ca2+/calmodulin-dependent protein kinase inhibitor, decreased the positive chronotrophic effect of relaxin (P < 0.001) but did not influence significantly the effect of relaxin on IR-ANP release in isolated perfused rat heart preparation. These results provide the first evidence that relaxin stimulates the secretion of ANP from isolated perfused rat hearts. Our results also suggest that relaxin modulates ANP secretion by activation of protein kinase C and cAMP-dependent protein kinase pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-95
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:8882168-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:8882168-Animals, pubmed-meshheading:8882168-Atrial Natriuretic Factor, pubmed-meshheading:8882168-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:8882168-Dose-Response Relationship, Drug, pubmed-meshheading:8882168-Enzyme Inhibitors, pubmed-meshheading:8882168-Heart, pubmed-meshheading:8882168-Heart Rate, pubmed-meshheading:8882168-Isoquinolines, pubmed-meshheading:8882168-Male, pubmed-meshheading:8882168-Perfusion, pubmed-meshheading:8882168-Protein Kinase C, pubmed-meshheading:8882168-Rats, pubmed-meshheading:8882168-Rats, Sprague-Dawley, pubmed-meshheading:8882168-Relaxin, pubmed-meshheading:8882168-Staurosporine, pubmed-meshheading:8882168-Stimulation, Chemical, pubmed-meshheading:8882168-Sulfonamides
pubmed:year
1996
pubmed:articleTitle
Relaxin stimulates atrial natriuretic peptide secretion in perfused rat heart.
pubmed:affiliation
Department of Pharmacology, University of Oulu, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't