Korean Circ J.  2012 Nov;42(11):761-768. 10.4070/kcj.2012.42.11.761.

Changes of Gene Expressions in Spontaneously Hypertensive Rat Model After Losartan Treatment

• Cha JH
• Lee HR
• Kim KC
• Cho MS
• Hong YM

• KMID: 2224976
• DOI: http://doi.org/10.4070/kcj.2012.42.11.761

Abstract

BACKGROUND AND OBJECTIVES
The renin angiotensin system seems to play an important role in the development of cardiac and vascular hypertrophy in hypertension. The changes in pathology, and gene expressions of the angiotensin II receptor type 1A (ATIA) and angiotensin converting enzyme (ACE) were investigated in order to explore the effects of losartan in spontaneously hypertensive rat (SHR) models.
MATERIALS AND METHODS
Twelve week-old male Wistar rats were grouped as follows: control (C) group, hypertension (H) group, and losartan (L) group in which SHR was treated with losartan (10 mg/kg/day). Western blot and reverse transcription-polymerase chain reaction analysis regarding seven genes such as endothelin-1, ACE, ATIA, neutrophil cytosolic factor, brain natriuretic peptide, troponin I, endothelial nitric oxide synthase were performed.
RESULTS
Systolic blood pressure was significantly decreased in the L group compared with the H group in weeks 3 and 5. ACE and ATIA proteins in the L group were lower than H group in week 5.
CONCLUSION
Losartan reduced blood pressure, cardiac hypertrophy and protein expressions of ACE and ATIA. Changes of protein expressions were more sensitive than changes in pathology. Further study is needed for the differing doses of losartan in SHR models.

Keyword

Hypertension; Receptors, angiotensin; Angiotensin converting enzyme; Gene expression

MeSH Terms

Blood Pressure
Blotting, Western
Cardiomegaly
Cytosol
Endothelin-1
Gene Expression
Humans
Hypertension
Hypertrophy
Losartan
Male
Natriuretic Peptide, Brain
Neutrophils
Nitric Oxide Synthase Type III
Peptidyl-Dipeptidase A
Proteins
Rats, Inbred SHR
Rats, Wistar
Receptors, Angiotensin
Renin-Angiotensin System
Troponin I
Endothelin-1
Losartan
Natriuretic Peptide, Brain
Nitric Oxide Synthase Type III
Peptidyl-Dipeptidase A
Proteins
Receptors, Angiotensin
Troponin I

Figure

• 

  Fig. 1 Systemic blood pressures after losartan treatment. Blood pressure was significantly higher in the H group compared with the C group on day 1, week 3, and week 5. Blood pressure was significantly lower in the L group compared with the H group in weeks 3 and 5. *Significantly different from group C group p<0.05, †Significantly different from group H group p<0.05. C: control, H: hypertension, L: losartan.

• 

  Fig. 2 Change of collagen by Masson's Trichrome staining in the heart tissues (×200). Collagen penetration in the H group was significantly higher than that in the C group. There was no statistically significant difference between the H and the L group but the L group showed a slight decrease in collagen. C: control, H: hypertension, L: losartan.

• 

  Fig. 3 Serum renin (A), aldosterone (B), ACE (C), angiotensin (D) levels after losartan treatment. *Significantly different from group C group p<0.05, †Significantly different from group H group p<0.05. C: control, H: hypertension, L: losartan.

• 

  Fig. 4 Endotehlin-1 (A), ACE (B), angiotensin II receptor type 1A (C), neutrophil cytosolic factor 1 (D) protein contents by western blot analysis in the heart tissues. *Significantly different from group C group p<0.05, †significantly different from group H group p<0.05. ET: endothelin, ACE: angiotensin converting enzyme, AT: angiotensin, NCF: neutrophil cytosolic factor; C: control, H: hypertension, L: losartan.

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