Arterial remodeling in B-type natriuretic peptide knock-out females

Sara J. Holditch, Claire A. Schreiber, John C Jr. Burnett, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 BNPs 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.

Original languageEnglish (US)
Article number25623
JournalScientific Reports
Volume6
DOIs
StatePublished - May 10 2016

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Brain Natriuretic Peptide
Vasculitis
Sex Characteristics
Polyarteritis Nodosa
Arteritis
Antihypertensive Agents
Aneurysm
Thrombosis
Necrosis
Animal Models
Stroke
Genotype
Pathology
Blood Pressure
Hypertension
Inflammation
Survival

ASJC Scopus subject areas

  • General

Cite this

Arterial remodeling in B-type natriuretic peptide knock-out females. / Holditch, Sara J.; Schreiber, Claire A.; Burnett, John C Jr.; Ikeda, Yasuhiro H.

In: Scientific Reports, Vol. 6, 25623, 10.05.2016.

Research output: Contribution to journalArticle

Holditch, Sara J. ; Schreiber, Claire A. ; Burnett, John C Jr. ; Ikeda, Yasuhiro H. / Arterial remodeling in B-type natriuretic peptide knock-out females. In: Scientific Reports. 2016 ; Vol. 6.
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