Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor
The Korean Journal of Physiology and Pharmacology
;
: 447-456, 2018.
Article
in English
| WPRIM
| ID: wpr-727574
ABSTRACT
Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576 µg/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor (AT₂R) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as TNF-α, MCP-1, IL-1β, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via AT₂R.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Plasma
/
Arterioles
/
Pulmonary Fibrosis
/
Blood Pressure
/
Angiotensins
/
Cytokines
/
Interleukin-6
/
Monocrotaline
/
Rats, Sprague-Dawley
/
Apoptosis
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2018
Type:
Article
Similar
MEDLINE
...
LILACS
LIS