Document Detail

Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium.
MedLine Citation:
PMID:  17082376     Owner:  NLM     Status:  MEDLINE    
Beta-adrenergic receptor (beta-AR) responsiveness is downregulated in left ventricular (LV) hypertrophy induced by chronic hypertension. While exercise training in hypertension enhances beta-AR responsiveness, the role of adenylyl cyclase remains unclear. The purpose of the present study was to test whether treadmill running in the spontaneously hypertensive rat (SHR) model improves LV responsiveness to forskolin (FOR) or the combination of FOR + isoproterenol (FOR+ISO). Female SHR (16-wk) were randomly placed into sedentary (SHR-SED; n = 7) or treadmill-trained (SHR-TRD; n = 8) groups. Wistar-Kyoto (WKY; n = 7) animals acted as normotensive controls. Langendorff, isovolumic LV performance was established at baseline and during incremental FOR infusion (1 and 5 micromol/l) and FOR+ISO (5 micromol/l + 1x10(-8) mol/l). Heart rate, systolic blood pressure, and heart-to-body weight ratio were lower in WKY relative to both SHR groups (P < 0.05). LV performance and heart rate significantly increased in all groups to a similar extent with incremental FOR infusion. However, in the presence of 5 micromol/l FOR, ISO increased LV developed pressure, positive change in LV pressure, and negative change in LV pressure to a greater extent in SHR-TRD relative to SHR-SED (P < 0.05). Phospholamban phosphorylation at the Thr17 was greater in SHR-TRD relative to SHR-SED and WKY (P < 0.05). Absolute LV developed pressure was moderately correlated with phospholamban phosphorylation at both the Ser16 (r = 0.64; P < 0.05) and Thr17 (r = 0.52; P < 0.05). Our data suggest that the adenylyl cyclase step in the beta-AR cascade is not downregulated in the early course of hypertension and that the enhanced beta-AR responsiveness with training is likely mediated at levels other than adenylyl cyclase. Our data also suggest that beta-AR inotropic responsiveness in the presence of direct adenylyl cyclase agonism is improved in trained compared with sedentary SHR hearts.
Stephen C Kolwicz; Hajime Kubo; Scott M MacDonnell; Steven R Houser; Joseph R Libonati
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-02
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  102     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-07     Completed Date:  2007-03-22     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  628-33     Citation Subset:  IM    
Department of Kinesiology, Temple Univ., Philadelphia, PA, USA.
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MeSH Terms
Adenylate Cyclase / physiology
Adrenergic beta-Agonists / pharmacology
Blood Pressure / drug effects
Calcium-Binding Proteins / metabolism*
Cyclic AMP / metabolism
Forskolin / pharmacology*
Heart Rate / drug effects
Hypertension / physiopathology*
Isoproterenol / pharmacology
Myocardial Contraction / drug effects*
Myocardium / metabolism*
Physical Conditioning, Animal / physiology*
Rats, Inbred WKY
Receptors, Adrenergic, beta / drug effects,  physiology
Ventricular Function, Left / drug effects
Grant Support
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Calcium-Binding Proteins; 0/Receptors, Adrenergic, beta; 0/phospholamban; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7683-59-2/Isoproterenol; EC Cyclase

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