Regional expression of natriuretic peptide receptors during the formation of arterial neointima in the rabbit.
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 upregulated as mitosis declined in the media and as a prominent neointima formed.
Brown
J
J
Physiological Laboratory, Cambridge, England.
Chen
Q
Q
D000818:Animals; D001158:Arteries / Q000293:injuries*; D001345:Autoradiography; D001665:Binding Sites; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004423:Ear / Q000098:blood supply; D006162:Guanylate Cyclase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism*; D015854:Up-Regulation
D008024:Ligands; D008565:Membrane Proteins; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP