title: Antagonism between the vascular renin-angiotensin and natriuretic peptide systems in vascular remodelling.
abstract: Vascular remodelling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests the pivotal role of vasoactive substances occurring in the blood vessel, such as angiotensin II (AII), in the control of vascular growth. We recently discovered that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced by vascular endothelial cells and can act as an endothelium-derived relaxing peptide. We also demonstrated gene expression of CNP and the ANP-B receptor, which is one of the three subtypes of the natriuretic peptide receptor and is specific to CNP in blood vessels in vivo. Thus, we propose the existence of a "vascular natriuretic peptide system (NPS)" similar to the vascular renin-angiotensin system (RAS). The present study showed that CNP exerted a growth-inhibitory action and antagonised the growth-promoting action of AII, which was mediated through the AII subtype 1 receptor in cultured vascular smooth muscle cells. In neointimal lesions of rat carotid artery, CNP gene transcript was detectable 2 weeks after balloon injury, and ANP-B receptor gene expression was augmented. These findings suggest that the vascular NPS is activated in proliferative vascular lesions, suppressing further proliferation by antagonising the action of the vascular RAS.
authors.affiliation: Department of Medicine, Kyoto University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000235:genetics / Q000502:physiology*; D006973:Hypertension / Q000209:etiology; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D009419:Nerve Tissue Proteins; D011506:Proteins; C058930:brain natriuretic peptide receptor; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D012313:RNA; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C