Document Detail


Regulation of L-type inward calcium channel activity by captopril and angiotensin II via the phosphatidyl inositol 3-kinase pathway in cardiomyocytes from volume-overload hypertrophied rat hearts.
MedLine Citation:
PMID:  21423294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heart failure can be caused by pro-hypertrophic humoral factors such as angiotensin II (Ang II), which regulates protein kinase activities. The intermingled responses of these kinases lead to the early compensated cardiac hypertrophy, but later to the uncompensated phase of heart failure. We have shown that although beneficial, cardiac hypertrophy is associated with modifications in ion channels that are mainly mediated through mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3K) activation. This study evaluates the control of L-type Ca(2+) current (I(Ca,L)) by the Ang II/PI3K pathway in hypertrophied ventricular myocytes from volume-overload rats using the perforated patch-clamp technique. To assess activation of the I(Ca,L) in cardiomyocytes, voltages of 350 ms in 10 mV increments from a holding potential of -85 mV were applied to cardiocytes, with a pre-pulse to -45 mV for 300 ms. Volume overload-induced hypertrophy reduces I(Ca,L), whereas addition of Ang II alleviates the hypertrophic-induced decrease in a PI3K-dependent manner. Acute administration of Ang II (10(-6) mol/L) to normal adult cardiomyocytes had no effect; however, captopril reduced their basal I(Ca,L). In parallel, captopril regressed the hypertrophy and inverted the Ang II effect on I(Ca,L) seemingly through a PI3K upstream effector. Thus, it seems that regression of cardiac hypertrophy by captopril improved I(Ca,L) partly through PI3K.
Authors:
Zikiar Alvin; Graham G Laurence; Bernell R Coleman; Aiqiu Zhao; Majd Hajj-Moussa; Georges E Haddad
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  89     ISSN:  1205-7541     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-22     Completed Date:  2012-02-13     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  206-15     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, College of Medicine, Howard University, WA 20059, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / pharmacology*,  therapeutic use
Animals
Calcium Channels, L-Type / physiology*
Captopril / pharmacology*,  therapeutic use
Cardiomegaly / drug therapy,  enzymology*
Male
Myocytes, Cardiac / drug effects*,  enzymology,  metabolism
Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  metabolism*
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
2G12 RR003048/RR/NCRR NIH HHS; G12 RR003048-14/RR/NCRR NIH HHS; GM08016-38/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channels, L-Type; 11128-99-7/Angiotensin II; 62571-86-2/Captopril; EC 2.7.1.137/Phosphatidylinositol 3-Kinase
Comments/Corrections

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