Clin Hypertens.  2016 ;22(1):12. 10.1186/s40885-016-0046-9.

Changes of blood pressure, abdominal visceral fat tissue and gene expressions in fetal programming induced rat model after amlodipine-losartan combination treatment

• Lee JH
• Lee H
• Lee SM
• Kang PJ
• Kim KC
• Hong YM

• KMID: 2380218
• DOI: http://doi.org/10.1186/s40885-016-0046-9

Abstract

BACKGROUND
There are a number of complications that can occur if there is under-nutrition during pregnancy followed by a period of rapid catch-up growth, including a higher chance of adult obesity, insulin resistance and hypertriglyceridemia. The purposes of this study were to investigate the effects of fetal under-nutrition during late pregnancy and lactation on blood pressure, visceral fat tissue, gene expressions and to evaluate changes after amlodipine- losartan combination treatment.
METHODS
The rats were divided into three groups: the control (C) group, the food restriction (FR: 50 % food restricted diet) group, and the CX group, which was treated with Cozaar XQ (amlodipine-losartan combination drug) in FR rats from postnatal 4 to 20 weeks. Masson's trichrome staining was performed in the heart tissues. The amount of abdominal visceral fat tissues was measured. Western blot analysis such as angiotensin converting enzyme (ACE), angiotensin II receptor type IA (ATIA), troponin I (Tn I) and endothelial nitric oxide synthase (eNOS) were performed.
RESULTS
Body weights were significantly higher in the FR group compared with the C group at weeks 8 and 20 and lower in the CX group at week 20. Blood pressure was significantly higher in the FR group compared with the C group at week 20 and lower in the CX group at weeks 12 and 20. The amount of abdominal visceral fat was significantly higher in the FR group compared with the C group at weeks 8, 12 and 20 and significantly lower in the CX group at weeks 16 and 20. Protein expression of ATIA and eNOS were significantly reduced in the CX group at weeks 16 and 20. ACE was significantly reduced in the CX group at week 20 and Tn I was significantly reduced in the CX group at week 16.
CONCLUSIONS
When there is fetal under-nutrition during pregnancy, it leads to obesity, high blood pressure, hypertriglyceridemia and several gene changes in offspring. Amlodipine-losartan combination treatment was able to lower obesity, hypertension, hypertriglyceridemia and several gene changes in rats suffering from fetal under-nutrition during pregnancy.

Keyword

Fetal programming; Blood pressure; Visceral fat; Gene expression

MeSH Terms

Adult
Animals
Blood Pressure*
Blotting, Western
Body Weight
Female
Fetal Development*
Gene Expression*
Heart
Humans
Hypertension
Hypertriglyceridemia
Insulin Resistance
Intra-Abdominal Fat*
Lactation
Losartan
Models, Animal*
Nitric Oxide Synthase Type III
Obesity
Peptidyl-Dipeptidase A
Pregnancy
Rats*
Receptors, Angiotensin
Troponin I
Losartan
Nitric Oxide Synthase Type III
Peptidyl-Dipeptidase A
Receptors, Angiotensin
Troponin I