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(Circulation Research. 1995;77:906.)
© 1995 American Heart Association, Inc.

Articles

Regional Expression of Natriuretic Peptide Receptors During the Formation of Arterial Neointima in the Rabbit

J. Brown, Q. Chen

From the Physiological Laboratory, Cambridge, England.

Correspondence to Dr J. Brown, Physiological Laboratory, Downing St, Cambridge, CB2 3EG, England.

Abstract In vitro evidence suggests that natriuretic peptide receptors (NPR)-B and NPR-C inhibit vascular smooth muscle (VSM) proliferation. NPR-B is guanylate cyclase-coupled and selectively activated by C-type natriuretic peptide (CNP)-(1-22). NPR-C is not guanylate cyclase-coupled and, unlike NPR-B, avidly binds atrial natriuretic peptide (ANP)-(1-28) as well as CNP-(1-22). Here, we investigate these receptors during the VSM proliferation and neointimal formation found 5, 7, and 20 days after compressing the central ear artery of the rabbit. Receptors were mapped autoradiographically using [¹²⁵I-Tyr⁰]CNP-(1-22), which binds NPR-B and NPR-C, and ¹²⁵I-ANP-(1-28), which binds NPR-C and NPR-A, another guanylate cyclase-coupled receptor. Normal tunica media had NPR-B–like binding sites, and the level of these did not change significantly after compression. Consistent with this, CNP-(1-22) stimulated cGMP production equally with membranes from normal or damaged arteries and was more effective than ANP-(1-28). Neointima, which became evident 5 to 7 days after arterial damage, expressed NPR-C–like sites and no detectable NPR-B–like binding. NPR-C–like sites also appeared on the media for the first time between 5 and 7 days after compression. Immunohistochemistry for proliferating cell nuclear antigen revealed widespread mitosis in VSM at 5 days after compression, but mitosis was virtually restricted to the neointima at and beyond 7 days after compression. Thus, whereas levels of NPR-B did not change significantly after arterial injury and NPR-A was not detected, NPR-C–like receptors were unregulated as mitosis declined in the media and as a prominent neointima formed.

Key Words: natriuretic peptides • receptors • neointima

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