J Korean Soc Hypertens.  2010 Dec;16(4):19-29.

Effects of Angiotensin II Type 2 Receptor on the Fibrosis of Diabetic Heart in the Otsuka Long-Evans Tokushima Fatty (OLETF) Rat

• Choi CU
• Park CG
• Cha DR
• Kim SH
• Shin SY
• Kim YK
• Na JO
• Kim JW
• Lim HE
• Kim EJ
• Rha SW
• Seo HS
• Oh DJ

Abstract

BACKGROUND
The objective of this study was to determine the effects of angiotensin II type 2 (AT2) receptor on the fibrosis of the diabetic heart and the hypertrophy of the aortic wall in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat.
METHODS
OLETF and age-matched Long-Evans Tokushima Otsuka (LETO) rats were treated with deoxycorticosterone acetate (DOCA) (25 mg/kg) with 1% NaCl in drinking water after receiving a left nephrectomy. Blood pressure was measured at eight and 16 weeks. At 16 week after the DOCA-salt treatment, a media cross sectional area of the aorta and myocardial fibrosis were evaluated, and the expressions of angiotensin II type 1 (AT1) and AT2 receptors were studied by real-time quantitative PCR and immunohistochemistry. The mRNA expression of beta-myosin heavy chain (beta-MHC) mineralocorticoid receptor was also determined.
RESULTS
DOCA-salt increased systolic blood pressure and diastolic blood pressure in both LETO and OLETF rats. The myocardial fibrosis of the left ventricle, media cross sectional area of the aorta, beta-MHC, and the AT2 receptor expression in the myocardium were increased in the OLETF + DOCA-salt treated rats compared to those of the LETO, LETO + DOCA-salt, and OLETF rats.
CONCLUSION
Cardiac fibrosis and hypertrophy of the aortic wall were progressed in diabetes combined with hypertension compared with diabetes only. The AT2 receptor could play a role in the progression of cardiac fibrosis and aortic wall hypertrophy.

Keyword

DOCA-salt; OLETF rat; LETO rat; AT1 receptor; AT2 receptor; fibrosis

MeSH Terms

Angiotensin II
Angiotensins
Animals
Aorta
Blood Pressure
Desoxycorticosterone
Drinking Water
Fibrosis
Heart
Heart Ventricles
Hypertension
Hypertrophy
Immunohistochemistry
Myocardium
Nephrectomy
Polymerase Chain Reaction
Rats
Rats, Inbred OLETF
Receptor, Angiotensin, Type 2
Receptors, Mineralocorticoid
RNA, Messenger
Ventricular Myosins
Angiotensin II
Angiotensins
Desoxycorticosterone
Drinking Water
RNA, Messenger
Receptor, Angiotensin, Type 2
Receptors, Mineralocorticoid
Ventricular Myosins