Effect of Transverse Aortic Constriction on Cardiac Structure, Function and Gene Expression in Pregnant Rats

Abstract

Background: There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. Methods: Pregnant (gestational day 5.5–8.5) and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC) or sham surgery. After 14.260.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV) pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. Results: Heart weight was increased by TAC (p,0.001) but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01), however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.162.4 vs 17.562.4 mmHg/mL, p,0.001) than in non-pregnant (28.261.7 vs 20.961.5 mmHg/mL, p = 0.06). However, it did not lead to overt heart failure in any group. In pregnant rats, a-MHC gene expression was reduced by TAC. Increased in the expression of b-MHC gene was higher in pregnant (5-fold) compared to non-pregnant rats (2-fold) after TAC (p = 0.001). Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. Conclusions: This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and nonpregnant rats following TAC indicated that afterload increase is less tolerated in pregnancy.