title: Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females.
abstract: Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb-/-) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb-/- females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb-/- female. This study highlights BNP's vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Holditch
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Schreiber
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine and Physiology, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000172:deficiency* / Q000235:genetics; D010488:Polyarteritis Nodosa / Q000235:genetics / Q000378:metabolism; D020303:Rats, Inbred Dahl; D012737:Sex Factors; D013997:Time Factors; D066253:Vascular Remodeling; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism*
chemical_list: D020097:Natriuretic Peptide, Brain