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Implication of C-type natriuretic peptide derived from vascular endothelial cells on blood pressure regulation

Clinical background

We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular?endothelial cells and proposed the existence of vascular natriuretic peptide system?composed of endothelial CNP and vascular smooth muscle guanylyl cyclase-B (GC-B), the?selective receptor for CNP, and implicated in the regulation of vascular tone, remodeling and?regeneration [15]. However the functional role of the natriuretic peptide system is still unclear, because markedly short stature of CNP or GC-B knockout mice could be hardly studied for blood pressure regulation [6].

In the present study, we have assessed the functional significance of this system in?the regulation of blood pressure in vivo using vascular endothelial cell-specific CNP?knockout (CNP ecKO) and vascular smooth muscle cell-specific GC-B knockout (GC-B smcKO) mice generated using the Cre/loxP system. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice [6]. CNP ecKO mice exhibited significantly increased blood pressure and an enhanced acute hypertensive response to nitric oxide synthetase inhibition by NG-nitro-L-arginine methyl ester (L-NAME). In addition, acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from CNP ecKO mice. Pulmonary vascular endothelial cells from CNP ecKO mice showed enhanced expression of genes encoding endothelin-1 (ET-1). In contrast, GC-B smcKO mice exhibited blood pressure similar to control mice, and acetylcholine-induced vasorelaxation was preserved in their isolated mesenteric arteries. Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in mesenteric arteries from GC-B smcKO mice.


These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B and indicate the implication of the vascular natriuretic peptide system in blood pressure control.


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Correspondence to Kazuwa Nakao.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Nakao, K., Nakao, K., Kuwahara, K. et al. Implication of C-type natriuretic peptide derived from vascular endothelial cells on blood pressure regulation. BMC Pharmacol Toxicol 16 (Suppl 1), A28 (2015).

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