Angiotensin-converting enzyme, bradykinin, and angiotensin II receptor binding in rat skin, tendon, and heart valves: an in vitro, quantitative autoradiographic study.
Angiotensin converting enzyme (ACE), an ectoenzyme bound to vascular endothelial cells, is also found at tissue sites (TACE) normally composed of fibrillar collagen and fibroblasts. For example, TACE is present in the adventitia of intramural coronary arteries and matrix of heart valves, as well as the fibrous tissue that follows the chronic administration of angiotensin II (AII) or aldosterone. At these sites bradykinin (BK) receptor but not AII receptor binding has been observed, suggesting that in fibrous tissue TACE uses BK as substrate. Dermis, subcutaneous tissue, and skeletal muscle tendon likewise are sites that are rich in fibrillar collagen but are different in their cellularity. Accordingly, we tested the hypothesis that TACE is normally present at sites of fibrous tissue and that BK--not AIK--receptor binding is anatomically coincident with TACE in keeping with its role as a kininase II. TACE and receptors for BK and AII were localized by quantitative in vitro autoradiography with [125I]351A, 125I[Tyr8]BK, and 125I[Sar1, Ile8]AII, respectively. Skin morphology was examined in serial full thickness sections obtained from the dorsum of Sprague-Dawley rats. We found the following: (1) high TACE binding occurred in subcutaneous connective tissue and heart valves that was displaced by lisinopril or 351A in a dose-dependent manner; (2) BK receptor binding and low density AII receptor binding were seen at these sites, where AII receptor binding was totally displaced by a type 1 (DuP753) but not a type 2 (PD123177) receptor antagonist; (3) ACE, BK, and AII receptor binding was not evident in epidermis, dermis, skeletal muscle, or tendon.(ABSTRACT TRUNCATED AT 250 WORDS)
Sun
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Department of Internal Medicine, University of Missouri-Columbia 65212.
Diaz-Arias
A A
AA
Weber
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KT
D000818:Animals; D001345:Autoradiography; D001920:Bradykinin / Q000378:metabolism*; D006351:Heart Valves / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013710:Tendons / Q000378:metabolism*
D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin