Reduction in left ventricular messenger RNA for transforming growth factor beta(1) attenuates left ventricular fibrosis and improves survival without lowering blood pressure in the hypertensive TGR(mRen2)27 Rat

Angiotensin II recruits transforming growth factor beta(1) (TGFbeta(1)) and is related to left ventricular fibrosis. However, it is unclear whether chronic in vivo reduction in left ventricular TGFbeta(1) expression blunts fibrosis and improves outcome in angiotensin II-dependent hypertension. Four-...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2000-11, Vol.36 (5), p.747-754
Main Authors: Pinto, Y M, Pinto-Sietsma, S J, Philipp, T, Engler, S, Kossamehl, P, Hocher, B, Marquardt, H, Sethmann, S, Lauster, R, Merker, H J, Paul, M
Format: Article
Language:English
Subjects:
Animals
Cardiomegaly - metabolism
Disease Models, Animal
Fibrosis - metabolism
Heart Diseases - metabolism
Heart Ventricles - chemistry
Heart Ventricles - drug effects
Hypertension - metabolism
Losartan - pharmacology
Male
ortho-Aminobenzoates - pharmacology
Rats
Rats, Inbred Strains
Rats, Sprague-Dawley
Receptors, Transforming Growth Factor beta - analysis
Receptors, Transforming Growth Factor beta - drug effects
Receptors, Transforming Growth Factor beta - metabolism
RNA, Messenger - analysis
RNA, Messenger - metabolism
Survival Analysis
Transforming Growth Factors - analysis
Transforming Growth Factors - drug effects
Transforming Growth Factors - metabolism
Ventricular Function
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Summary:Angiotensin II recruits transforming growth factor beta(1) (TGFbeta(1)) and is related to left ventricular fibrosis. However, it is unclear whether chronic in vivo reduction in left ventricular TGFbeta(1) expression blunts fibrosis and improves outcome in angiotensin II-dependent hypertension. Four-week-old male hypertensive TGR(mRen2)27 (Ren2) rats received either normal food, low-dose losartan (0.5 mg. kg(-1). d(-1)), or tranilast (a nonspecific TGFbeta inhibitor; 400 mg. kg(-1). d(-1)) (n=10 for each group) for 12 weeks and were compared with Sprague-Dawley control rats. The effect of tranilast on survival was evaluated in 34 additional untreated homozygous Ren2 rats. Tranilast or low-dose losartan did not lower blood pressure. However, the increase in left ventricular weight (Ren2 versus SD 3.1+/-0.16 versus 2.1+/- 0.06 mg/g body wt; P
ISSN:1524-4563
DOI:10.1161/01.HYP.36.5.747