Linked Life Data

16424797

Source:http://linkedlifedata.com/resource/pubmed/id/16424797

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-20
pubmed:abstractText
Targeting aldosterone synthesis and/or release represents a potentially useful approach to the prevention of cardiovascular disease. Aldosterone production is stimulated by angiotensin II (Ang II) or extracellular K+ and is mediated mainly by Ca2+ influx into adrenal glomerulosa cells through T-type calcium channels. We therefore examined the effects of efonidipine, a dual T-type/L-type Ca2+ channel blocker, on aldosterone secretion in the H295R human adrenocarcinoma cell line; 100 nmol/L Ang II and 10 mmol/L K+ respectively increased aldosterone secretion from H295R cells 12-fold and 9-fold over baseline. Efonidipine dose-dependently inhibited both Ang II- and K+-induced aldosterone secretion, and nifedipine, an L-type Ca2+ channel blocker, and mibefradil, a relatively selective T-type channel blocker, similarly inhibited Ang II- and K+-induced aldosterone secretion, but were much less potent than efonidipine. Efonidipine also lowered cortisol secretion most potently among these drugs. Notably, efonidipine and mibefradil also significantly suppressed Ang II- and K+-induced mRNA expression of 11-beta-hydroxylase and aldosterone synthase, which catalyze the final two steps in the aldosterone synthesis, whereas nifedipine reduced only K+-induced enzyme expression. These findings suggest that efonidipine acts via T-type Ca2+ channel blockade to significantly reduce aldosterone secretion, and that this effect is mediated, at least in part, by suppression of 11-beta-hydroxylase and aldosterone synthase expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells.
pubmed:affiliation
First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't