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AT1, AT2 and mas Receptor Expression in the Uteroplacental Unit of Normotensive and Hypertensive Rats
Author(s) -
Brosnihan KB,
Neves LAA,
Coveleskie K,
Stovall K,
Gallagher PE,
Diz DI
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a345-a
Subject(s) - angiotensin ii receptor type 1 , medicine , endocrinology , losartan , placenta , angiotensin ii , receptor , uterus , fetus , chemistry , biology , pregnancy , genetics
Late pregnancy is associated with enhanced uterine and placental levels of angiotensin peptides but a marked decrease in Ang‐(1–7) occurs during hypertensive pregnancy. We investigated AT 1 , AT 2 and mas /AT 1‐7 receptors in the uteroplacental unit of normal (NP) and reduced uterine perfusion pressure (RUPP) pregnant rats at late gestation by receptor autoradiography using 125 I‐Sar 1 ‐Thr 8 ‐Ang II and reverse transcriptase real time PCR. RUPP rats had higher MAP (109±1 vs 121±1 mmHg, p<0.05). In myo‐ and endometrium of virgin uterus there was 80‐90% competition with the AT 1 receptor antagonist losartan and ~10–20% competition with AT 2 / mas receptor antagonists (PD123319 and D‐Ala). AT 1 binding density was higher in myo‐ vs. endometrium (142 ± 68 vs 50 ± 34, p<0.01). In NP and RUPP, AT 1 binding predominates in the mesometrial triangle with little to no competition with PD or D‐Ala. The AT 1 density was 1.6 fold greater in RUPP vs. NP (p<0.05). AT 1 , AT 2 and mas receptor mRNA was lower in uterus of NP (58%, 98% and 76%, p<0.05) and RUPP (55%, 97% and 81%) vs virgin. AT 1 receptor binding and mRNA in fetal and fetal/maternal placenta respectively were similar between RUPP and NP. In the fetal placenta of NP, 23% competition occurred with PD (p=.0505) and in RUPP there was 17% competition with D‐Ala. AT 1 receptor accounts for the majority of binding in the uteroplacental unit of both NP and RUPP. During normal and hypertensive pregnancy expression of all receptors are reduced in the uteroplacental unit; however in the fetal placenta there is a shift from AT 2 to mas /AT 1‐7 receptors in hypertensive pregnancy. Supported by NHLBI51952 and AHA 0565390U