Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

Li, J., Wang, J. C., Russell, F. D. and Molenaar, P. (2005) Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II. British Journal of Pharmacology, 145 4: 432-440.


Author Li, J.
Wang, J. C.
Russell, F. D.
Molenaar, P.
Title Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II
Journal name British Journal of Pharmacology  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2005
Sub-type Article
DOI 10.1038/sj.bjp.0706217
Volume number 145
Issue number 4
ISSN 0007-1188
Start page 432
End page 440
Total pages 9
Editor H. Rang
Place of publication London, U.K.
Publisher Nature Publishing Group
Collection year 2005
Language eng
Subject C1
321003 Cardiology (incl. Cardiovascular Diseases)
730106 Cardiovascular system and diseases
Abstract 1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human ( 14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 mu M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P < 0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P > 0.1). FK506 had no effect on contractile force (P = 0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P = 0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC epsilon compared to samples incubated without PKCe. 6 Endogenous cardiostimulants which activate G alpha q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.
Keyword Calcineurin
Heart Failure
Receptors
Signal Transduction
Hypertrophy
Pharmacology & Pharmacy
Protein-kinase-c
Beta(2)-adrenergic Receptors
Cardiomyocyte Hypertrophy
Cardiac-hypertrophy
Hastens Relaxation
Troponin-i
Failure
Phosphorylation
Phosphatase
Inhibition
Q-Index Code C1

 
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