Document Detail


Effects of cardiac overexpression of type 6 adenylyl cyclase affects on the response to chronic pressure overload.
MedLine Citation:
PMID:  20562336     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenylyl cyclase (AC) type 5 (AC5) and AC type 6 (AC6) are the two major AC isoforms in the heart. Cardiac overexpression of AC6 has been shown to be protective in response to several interventions. In this investigation, we examined the effects of chronic pressure overload in AC6 transgenic (TG) mice. In the absence of any stress, AC6 TG mice exhibited enhanced contractile function compared with their wild-type (WT) littermates, i.e., increased (P < 0.05) left ventricular (LV) ejection fraction (EF) (75 +/- 0.9 vs. 71 +/- 0.5%) and LV dP/dt (7,850 +/- 526 vs. 6,374 +/- 315 mmHg/s). Forskolin (25 microg x kg(-1) x min(-1) for 5 min) increased LVEF more (P < 0.05) in AC6 TG mice (14.8 +/- 1.0%) than in WT mice (7.7 +/- 1.0%). Also, isoproterenol (0.04 microg x kg(-1) x min(-1) for 5 min) increased LVEF more (P < 0.05) in AC6 TG mice (18.0 +/- 1.2%) than in WT mice (11.6 +/- 2.1%). Pressure overload, induced by 4 wk of transverse aortic constriction (TAC), increased the LV weight-to-body weight ratio and myocyte cross-sectional area similarly in both groups, but reduced LVEF more in AC6 TG mice (22%) compared with WT mice (9%), despite the higher starting level of LVEF in AC6 TG mice. LV systolic wall stress increased more in AC6 TG mice than in WT mice, which could be responsible for the reduced LVEF in AC6 TG mice with chronic pressure overload. In addition, LV dP/dt was no longer elevated in AC6 TG mice after TAC compared with WT mice. LV end-diastolic diameter was also greater (P < 0.05) in AC6 TG mice (3.8 +/- 0.07 mm) than in WT mice (3.6 +/- 0.05 mm) after TAC. Thus, in contrast to other interventions previously reported to be salutary with cardiac AC6 overpression, the response to chronic pressure overload was not; actually, AC6 TG mice fared worse than WT mice. The mechanism may be due to the increased LV systolic wall stress in AC6 TG mice with chronic pressure overload.
Authors:
Aziz Guellich; Shumin Gao; Chull Hong; Lin Yan; Thomas E Wagner; Sunil K Dhar; Bijan Ghaleh; Luc Hittinger; Kosaku Iwatsubo; Yoshihiro Ishikawa; Stephen F Vatner; Dorothy E Vatner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-18
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-09-22     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H707-12     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / genetics,  metabolism*
Analysis of Variance
Animals
Apoptosis / drug effects,  physiology
Colforsin / pharmacology
Echocardiography
Heart / drug effects,  physiopathology*
Heart Rate / drug effects,  physiology
Heart Ventricles / drug effects,  metabolism*,  physiopathology
Hemodynamics
Hypertrophy, Left Ventricular / metabolism*,  physiopathology
Isoproterenol
Mice
Mice, Transgenic
Myocardial Contraction / drug effects,  physiology
Myocardium / metabolism*
Stress, Physiological / physiology
Ventricular Dysfunction, Left / metabolism*,  physiopathology
Grant Support
ID/Acronym/Agency:
AG-014121/AG/NIA NIH HHS; AG-023137/AG/NIA NIH HHS; AG-027211/AG/NIA NIH HHS; HL-033107/HL/NHLBI NIH HHS; HL-059139/HL/NHLBI NIH HHS; HL-069020/HL/NHLBI NIH HHS; HL-069752/HL/NHLBI NIH HHS; HL-095888/HL/NHLBI NIH HHS; R01 HL033107/HL/NHLBI NIH HHS; R01 HL093481/HL/NHLBI NIH HHS; R01 HL095888/HL/NHLBI NIH HHS; R01 HL102472/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
1F7A44V6OU/Colforsin; EC 4.6.1.1/Adenylate Cyclase; EC 4.6.1.1/adenylyl cyclase 6; L628TT009W/Isoproterenol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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