Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

Abstract

We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular endothelial cells and proposed the existence of a vascular natriuretic peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B (GC-B), the CNP receptor, and involved in the regulation of vascular tone, remodeling, and regeneration. In this study, we assessed the functional significance of this system in the regulation of blood pressure in vivo using vascular endothelial cell–specific CNP knockout and vascular smooth muscle cell–specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial cell–specific CNP knockout mice exhibited significantly increased blood pressures and an enhanced acute hypertensive response to nitric oxide synthetase inhibition. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from endothelial cell–specific CNP knockout mice. In addition, endothelin-1 gene expression was enhanced in pulmonary vascular endothelial cells from endothelial cell–specific CNP knockout mice, which also showed significantly higher plasma endothelin-1 concentrations and a greater reduction in blood pressure in response to an endothelin receptor antagonist than their control littermates. By contrast, vascular smooth muscle cell–specific GC-B knockout mice exhibited blood pressures 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 vascular smooth muscle cell–specific GC-B knockout 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.

Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance

“…Most circulating CNP is thought to originate from cartilage and vessels (26). Serial expression patterns of CNP in blood vessels were identical to those in tibial cartilage and vertebrae.…”

A Highly-sensitized Response of B-type Natriuretic Peptide to Cardiac Ischaemia Quantified by Intracoronary Pressure Measurements

“…ANP restores the attenuated cardioprotective effects in diabetic hearts, possibly due to the increase in endothelial nitric oxide synthesis (eNOS) expression and subsequent increase in NO activity 27 . Moreover, CNP induces vascular relaxation by endothelium-dependent and endothelium-independent mechanisms 28,29 . Although more precise human studies are required, the interaction left circumflex coronary artery; RCA, right coronary artery; LMT, left main trunk; VD, vessel disease; LVEF, left ventricular ejection fraction; LVEDP, left ventricular end-diastolic pressure; CI, cardiac index; SBP, systolic blood pressure; DBP, diastolic blood pressure.…”

Overexpression of C-type Natriuretic Peptide in Endothelial Cells Protects against Insulin Resistance and Inflammation during Diet-induced Obesity

“…In comparison, the activity of exogenous CNP is weaker than that of ANP, and exogenous CNP has activities without effects on blood pressure 59 – 61 ; both of these possibilities are consistent with the results seen in our endothelial cell–specific CNP Tg mice (Supplementary Table S2 ). In addition, deletion of endothelium-derived CNP recently was shown to increase blood pressure 62 , 63 . Therefore, CNP’s effects on the cardiovascular system may differ depending on its source (that is, exogenous or endogenous).…”