Selective down-regulation of AT2 receptors in uterine arteries from pregnant ewes given 24-h intravenous infusions of angiotensin II.
Previously, we showed that uterine arteries from late gestation pregnant ewes infused intravenously with angiotensin II (Ang II) for 24 h, displayed heightened responsiveness to Ang II in vitro. Furthermore, we found that a small population of ewes with a "preeclampsia-like" disorder also displayed this. Therefore, we have investigated the density and affinity of Ang II receptor subtypes in the uterine arteries from these groups. Ang II receptor binding was measured using 125I [Sar1Ile8] Ang II. Proportions of AT1 and AT2 receptors were determined by inhibiting 125I [Sar1Ile8] Ang II with losartan (AT1 antagonist) or PD 123319 (AT2 antagonist). Uterine arteries from 24-h Ang II-infused ewes had a lower proportion of AT2 receptors (56.2+/-2.3%) than control (saline-infused) ewes (84.1+/-1.0%; P<0.05). The density of AT2 receptors was reduced (P<0.05) while the density of AT1 receptors was not different. Thus, 24-h infusions of Ang II selectively down-regulated AT2 receptors in the uterine artery, resulting in heightened Ang II reactivity. By contrast, the binding properties of Ang II receptor subtypes in uterine arteries from ewes with the "preeclampsia-like" disorder were not different from control ewes.
McMullen
J R
JR
School of Physiology and Pharmacology, University of New South Wales, 2052, Sydney, Australia.
Gibson
K J
KJ
Lumbers
E R
ER
Burrell
J H
JH
D000804:Angiotensin II / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002404:Catheterization; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D007262:Infusions, Intravenous; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000097:blood; D012083:Renin / Q000097:blood; D012756:Sheep; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012083:Renin