Alterations in the renin-angiotensin system in a rat model of human preeclampsia.
OBJECTIVE
Preeclampsia is a hypertensive disorder unique to pregnancy in which elevated levels of marinobufagenin (MBG) have been reported. The renin-angiotensin system (RAS) may also play a role in the pathogenesis of preeclampsia. The aim of our study was to evaluate the status of the RAS in a rat model of preeclampsia characterized by hypertension, proteinuria, excessive weight gain and intrauterine growth restriction.


METHODS
We evaluated the components of the RAS in 5 groups of animals: nonpregnant control; normal pregnant (NP); pregnant rats which received injections of desoxycorticosterone acetate and 0.9% saline as their drinking water (PDS); normal pregnant rats injected with MBG (NPM), and PDS rats to which resibufogenin (RBG) had been administered (PDSR). RBG is an antagonist of MBG differing in structure from MBG only in the absence of a hydroxyl group in the beta-5 position.


RESULTS
Plasma levels of active renin, renin and Ang II were significantly lower in PDS and NPM compared to NP and PDSR rats (p < 0.05). However, placental levels of these components were increased significantly in PDS and NPM compared to NP and PDSR rats (p < 0.05). Placental AT(1) receptor expression was significantly higher in PDS and NPM compared to NP and PDSR rats (p < 0.05).


CONCLUSIONS
(1) The peripheral RAS is downregulated, and the uteroplacental RAS is upregulated in this rat model of preeclampsia; (2) MBG is involved in the causation of these alterations, and (3) RBG prevents these changes.
Uddin
Mohammad Nasir
MN
Division of Nephrology and Hypertension, Department of Medicine, Texas A&M University Health Science Center College of Medicine and Scott & White Memorial Hospital, Temple, TX 76508, USA.
Agunanne
Enoch
E
Horvat
Darijana
D
Puschett
Jules B
JB
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D003900:Desoxycorticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012083:Renin