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Transforming growth factor-β inhibition and endothelin receptor blockade in rats with monocrotaline-induced pulmonary hypertension.

Abstract：

:Transforming growth factor-β (TGF-β) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertension was induced by single monocrotaline injection (60 mg/kg) in 75 Wistar rats and 15 rats served as controls. Intervention groups consisted of treatment with an antibody against TGF-β-ligand, bosentan, both or none, initiated four weeks after monocrotaline injection. Right ventricular systolic pressure, pulmonary vascular remodeling, and exercise tolerance were evaluated eight weeks after monocrotaline injection. Either treatment, alone or in combination, lowered mortality. Comparable efficacy was found in the three treatment groups in terms of right ventricular systolic pressure (~45% decrease) and hypertrophy (~30% decrease), as well as exercise capacity. The three treatment groups equally ameliorated pulmonary vascular remodeling, evidenced by decreased vessel-wall thickness (in vessels 50-200 μm) and a smaller number of pre-capillary arterioles (< 50 μm) with a muscularized media. Treatment either with an antibody against TGF-β or with endothelin receptor blockade are equally effective in experimental pulmonary hypertension. Their combination provides no added benefit, indicating common mechanisms of action.

journal_name

Pulm Circ

journal_title

Pulmonary circulation

authors

Megalou AJ,Glava C,Vilaeti AD,Oikonomidis DL,Baltogiannis GG,Papalois A,Vlahos AP,Kolettis TM

doi

10.4103/2045-8932.105034

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

461-9

issue

4

eissn

2045-8932

issn

2045-8940

pii

PC-2-461

journal_volume

2

pub_type

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