J Korean Soc Hypertens.  2011 Mar;17(1):28-36. 10.5646/jksh.2011.17.1.28.

Effects of Bosentan Treatment on Angiotensin Converting Enzyme in Monocrotaline Induced Pulmonary Hypertension Rats

Affiliations
  • 1Deparment of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea. hongym@chollian.net

Abstract

BACKGROUND
Pulmonary artery hypertension is characterized by persistent increase of vascular resistance, and is associated with right ventricle failure. We investigated changes of plasma renin, serum aldosterone, angiotensin converting enzyme (ACE) concentrations, ACE gene expressions and protein contents after bosentan treatment.
METHODS
Six-week-old male Sprague-Dawley rats were divided into three groups: control (C) group, monocrotaline (M) group, and bosentan (B) group. Groups M and B were subcutaneously administered with 60 mg/kg of monocrotaline. In group B, 20 mg/kg/day of bosentan was administered by gavage twice a day. The rats were sacrificed after 1, 5, 7, 14, and 28 days. Changes of ACE gene expressions were analyzed by reverse transcription-polymerase chain reaction. Also, plasma renin, serum aldosterone, and ACE levels were measured.
RESULTS
Serum aldosterone levels were significantly increased in group M compared with group C and significantly decreased after bosentan treatment on day 28. Serum ACE concentrations were significantly decreased compared with group M after bosentan treatment on day 28. Gene expressions of ACE were significantly increased in group M compared with group C on day 5 and significantly decreased after bosentan treatment on day 7 and 14. ACE protein contents significantly increased in group M compared with group C in week 2 and 4. It significantly decreased after bosentan treatment in week 2.
CONCLUSIONS
The renin-angiotensin system is associated with pulmonary artery hypertension. To investigate the effects of bosentan on the renin-angiotensin system in pulmonary artery hypertension, further studies on the effects of bosentan according to different doses are required in the future.

Keyword

Pulmonary artery hypertension; Monocrotaline; Bosentan; Angiotensin converting enzyme; Gene expression

MeSH Terms

Aldosterone
Angiotensins
Animals
Gene Expression
Heart Ventricles
Humans
Hypertension
Hypertension, Pulmonary
Male
Monocrotaline
Peptidyl-Dipeptidase A
Plasma
Pulmonary Artery
Rats
Rats, Sprague-Dawley
Renin
Renin-Angiotensin System
Sulfonamides
Vascular Resistance
Aldosterone
Angiotensins
Monocrotaline
Peptidyl-Dipeptidase A
Renin
Sulfonamides
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