Effects of placental insufficiency on the ovine fetal renin-angiotensin system

We postulated that chronic placental insufficiency would be associated with reduced expression of renal renin and angiotensinogen genes in the fetal s heep. Placental development was restricted in ewes by removing the majority of caruncles prior to mating (placentally restricted (PR) group). The weig hts of PR fetuses were significantly reduced (P < 0.05, 2.98+/-0.33 kg) com pared to control fetuses (4.20 +/- 0.30 kg). Kidney weights were also signi ficantly reduced in the PR fetuses (P < 0.05, 8.4+/-0.9 g) compared with co ntrol fetuses (12.2+/-1.3 g). The ratios of renal renin/beta-actin mRNA lev els were significantly reduced in PR fetuses (P < 0.001, 0.35+/-0.02) when compared to control animals (0.98+/-0.13). The renal angiotensinogen mRNA/1 8S rRNA ratio was significantly lower (P < 0.05, 0.28+/-0.13) in PR fetuses compared with control fetuses (0.72+/-0.10), while hepatic angiotensinogen was unaffected. There was a positive correlation between renal renin mRNA and rend angiotensinogen mRNA levels (r = 0.65, P < 0.05, n = 12). It is un likely that these changes in renal angiotensinogen and renin mRNA were due to the small increment in plasma cortisol levels (< 5 nmol l(-1)). There wa s, however, a positive correlation between arterial Pot and renal renin mRN A (r(2) = 0.77, P < 0.01). Plasma renin levels were not different between t he two groups. Thus, restriction of nutrient and oxygen supply throughout f etal life was associated with suppression of renal renin and renal angioten sinogen gene expression, with no effect on hepatic angiotensinogen mRNA lev els. This specific suppression of fetal renal renin and angiotensinogen exp ression could alter the activity of the intrarenal RES and so affect growth and development of the kidney.