Combined angiotensin and endothelin receptor blockade attenuates adverse cardiac remodeling post-myocardial infarction in the rat: possible role of transforming growth factor beta(1)

A Tzanidis, S Lim, R D Hannan, F See, A M Ugoni, H Krum
Journal of Molecular and Cellular Cardiology 2001, 33 (5): 969-81
A. Tzanidis, S. Lim, R. D. Hannan, F. See, A. M. Ugoni and H. Krum. Combined Angiotensin and Endothelin Receptor Blockade Attenuates Adverse Cardiac Remodeling Post-Myocardial Infarction in the Rat: Possible Role of Transforming Growth Factor beta(1). Journal of Molecular and Cellular Cardiology (2001) 33, 969-981. Myocardial infarction (MI) is associated with activation of the vasoconstrictor peptides, angiotensin II (AngII) and endothelin-1 (ET-1), which are thought to contribute to adverse cardiac remodeling and dysfunction. The present study sought to determine whether combined AngII and ET receptor blockade improves cardiac remodeling over individual treatments in an experimental model of left ventricular myocardial infarction (LVMI) in the rat. Groups of eight female Sprague-Dawley rats were randomized at 24 h post-LVMI to 1 week treatment with either vehicle, an ET(A/B)receptor antagonist (bosentan), an AT(1)receptor antagonist (valsartan), or combined treatment. Vehicle-treated animals developed LV dysfunction with extensive accumulation of collagen type I and increased alpha(1)(I) procollagen mRNA compared to sham controls. Whilst individual receptor blockade with either bosentan or valsartan reduced LVEDP towards sham control levels, there were no significant changes to myocardial collagen deposition in comparison to vehicle. In contrast, improved ventricular function by combined treatment was associated with reduced type I collagen deposition within left ventricular non-infarct regions, as well as reduced peptide distribution and cardiac gene expression of the profibrogenic peptide, transforming growth factor beta(1)(TGF beta(1)). These data demonstrate that combined AngII and ET receptor blockade has beneficial effects on myocardial fibrogenesis over individual treatments during adverse cardiac remodeling early post-MI.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"