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Vascular Biology |
From the Departments of Medicine (S.P.B., L.S.L., Z.L.), Comparative Medicine (B.E.O.), and Pathology (C.L.C.), Oregon Health and Science University and Portland VA Medical Center, Portland, Ore, and the Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology (R.C.S.), College of Veterinary Medicine, Washington State University, Pullman.
Correspondence to Susan P. Bagby, MD, Professor of Medicine, Division of Nephrology, Oregon Health and Science University, 3314 SW US Veterans Hospital Rd, Suite 262, Portland, OR 97201-2940. E-mail bagbys{at}ohsu.edu
Objective To identify vascular cells capable of responding to angiotensin II (Ang II) generated in conduit arteries, we examined the Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R) in the thoracic aorta (TA) and abdominal aorta (AA) and branches in 90-day fetal, 3-week postnatal, and 6-month adult microswine.
Methods and Results By autoradiography (125I-[Sar1Ile8]-Ang II with or without AT1R- or AT2R-selective analogues or 125I-CGP 42112), there were striking rostrocaudal differences in (1) AT2R binding at all ages (prominent in AA wall and branches, sparse in TA wall and branches) and (2) a non-AT2R binding site for CGP 42112 (consistently evident in postnatal TA and branches but absent in AA and branches). Furthermore, patterns of AT2R distribution in infradiaphragmatic arteries were developmentally distinct. In fetal AAs, high-density AT2Rs occupied the inner 60% of the medial-endothelial wall. In postnatal AAs, AT2Rs were sparse in the medial-endothelial wall but prominent in a circumferential smooth muscle
-actinnegative cell layer at the medial-adventitial border, occupying
20% to 25% of the AA cross-sectional area. AT1R density in the TA and AA medial-endothelial wall increased with age, whereas AT2R density decreased after birth.
Conclusions A novel AT2R-positive cell layer confined to postnatal infradiaphragmatic arteries physically links adventitial and medial layers, appears optimally positioned to transduce AT2R-dependent functions of local Ang II, and suggests that adventitial Ang II may elicit regionally distinct vascular responses.
Key Words: neural AT2R quantitative autoradiography vascular renin-angiotensin system developing aorta CGP 42112
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