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 sheep. Placental development was restricted in ewes by removing the majority of caruncles prior to mating (placentally restricted (PR) group). The weights of PR fetuses were significantly reduced (P < 0.05, 2.98 +/- 0.33 kg) compared to control fetuses (4.20 +/- 0.30 kg). Kidney weights were also significantly reduced in the PR fetuses (P < 0.05, 8.4 +/- 0.9 g) compared with control fetuses (12.2 +/- 1.3 g). The ratios of renal renin/-actin mRNA levels 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/18S 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 renal angiotensinogen mRNA levels (r = 0.65, P < 0.05, n = 12). It is unlikely that these changes in renal angiotensinogen and renin mRNA were due to the small increment in plasma cortisol levels (< 5 nmol l-1). There was, however, a positive correlation between arterial PO2 and renal renin mRNA (r2 = 0.77, P < 0.01). Plasma renin levels were not different between the two groups. Thus, restriction of nutrient and oxygen supply throughout fetal life was associated with suppression of renal renin and renal angiotensinogen gene expression, with no effect on hepatic angiotensinogen mRNA levels. This specific suppression of fetal renal renin and angiotensinogen expression could alter the activity of the intrarenal RAS and so affect growth and development of the kidney.
Zhang
D Y
DY
School of Physiology, The University of New South Wales, Sydney, Australia.
Lumbers
E R
ER
Simonetta
G
G
Wu
J J
JJ
Owens
J A
JA
Robinson
J S
JS
McMillen
I C
IC
D000808:Angiotensinogen / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D008099:Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D012260:Ribonucleases / Q000378:metabolism; D012756:Sheep
D012333:RNA, Messenger; D000808:Angiotensinogen; D012260:Ribonucleases; D012083:Renin; D006854:Hydrocortisone