Monoclonal antibody against brain natriuretic peptide and characterizationof brain natriuretic peptide-transgenic mice

Objective Brain natriuretic peptide (BNP) is a ventricular hormone with nat riuretic, diuretic and vasodilatory actions, Acute infusion of BNP reduces cardiac pre- and after-load in healthy and diseased subjects, but its long- term therapeutic usefulness remains unclear, Design: We prepared a monoclonal antibody specific to mouse BNP, and charac terized transgenic mice overexpressing BNP in the liver (BNP-Tg mice) as a model of its chronic overproduction. Methods: Radioimmunoassay and neutralization experiments using the monoclon al antibody, KY-mBNIP-I, were performed in BNP-Tg mice in conjunction with examinations of blood pressure (BP) and other markers for body fluid homeos tasis, Results: We developed highly sensitive radioimmunoassay to mouse BNP. In BN P-Tg mice, the plasma BNP concentration increased more than 100-fold, while ventricular BNP concentration did not alter, suggesting that ventricular B NP production was not down-regulated in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than nontransgenic (nonTg) littermates, a ccompanied with marked reduction in the atrial natriuretic peptide (ANP) co ncentration, that may be due to binding of circulating BNP to the natriuret ic peptide receptors, BNP-Tg mice showed significantly low arterial BP, and a bolus intraperitoneal administration of KY-mBNIP-I completely abolished enhanced cGMP excretion in the urine and significantly increased the systol ic BP, Conclusion: These results suggested that biological actions of BNP last and reduce cardiac overload in its longterm overproduction in the transgenic m ouse model. I Hypertens 19:475-483 (C) 2001 Lippincott Williams & Wilkins.