Hypertension in adult growth restricted offspring is associated with activation of the renin angiotensin system.

Abstract

Reduced uterine perfusion initiated in late gestation in the rat results in intrauterine growth restriction (IUGR) and development of hypertension between 4 to 6 weeks of age in male growth restricted offspring. Hypertension in adult (12 week old) male growth restricted offspring is abolished by blockade of the renin angiotensin system (RAS) indicating a role for RAS involvement in IUGR-induced hypertension. Thus, the purpose of this study was to measure expression of renal components of the RAS in male growth restricted offspring. At 12 weeks of age renal mRNA expression of angiotensinogen (Aogen) as determined by real time PCR was increased 4-fold in the cortex and 2-fold in the medulla of growth restricted offspring as compared to control offspring. Renal mRNA expression of renin was also significantly elevated at 12 weeks of age in both the cortex, a greater than 2.5 fold increase, and medulla, a greater than 2 fold increase, in growth restricted offspring relative to control. At 6 weeks of age no difference in Aogen or renin mRNA expression was observed in either the cortex or medulla of growth restricted offspring as compared to control offspring. However, at birth renal expression of renin mRNA was significantly decreased in growth restricted offspring relative to control offspring. Therefore, these data suggests that suppression of the RAS is present at birth in male growth restricted offspring with later activation of the RAS occurring after development of hypertension in this model of fetal programming. NIH HL074927.