Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice.
OBJECTIVE
Brain natriuretic peptide (BNP) is a ventricular hormone with natriuretic, 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.


METHODS
We prepared a monoclonal antibody specific to mouse BNP, and characterized transgenic mice overexpressing BNP in the liver (BNP-Tg mice) as a model of its chronic overproduction.


METHODS
Radioimmunoassay and neutralization experiments using the monoclonal antibody, KY-mBNP-I, were performed in BNP-Tg mice in conjunction with examinations of blood pressure (BP) and other markers for body fluid homeostasis.


RESULTS
We developed highly sensitive radioimmunoassay to mouse BNP. In BNP-Tg mice, the plasma BNP concentration increased more than 100-fold, while ventricular BNP concentration did not alter, suggesting that ventricular BNP production was not down-regulated in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than nontransgenic (nonTg) littermates, accompanied with marked reduction in the atrial natriuretic peptide (ANP) concentration, that may be due to binding of circulating BNP to the natriuretic peptide receptors. BNP-Tg mice showed significantly low arterial BP, and a bolus intraperitoneal administration of KYmBNP-I completely abolished enhanced cGMP excretion in the urine and significantly increased the systolic BP.


CONCLUSIONS
These results suggested that biological actions of BNP last and reduce cardiac overload in its longterm overproduction in the transgenic mouse model.
Nakagawa
M
M
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Tanaka
I
I
Mukoyama
M
M
Suga
S
S
Ogawa
Y
Y
Tamura
N
N
Ishibashi
R
R
Goto
M
M
Nakagawa
O
O
Sugawara
A
A
Nakao
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000502:physiology; D001794:Blood Pressure; D006321:Heart / Q000033:anatomy & histology; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020097:Natriuretic Peptide, Brain / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D009500:Neutralization Tests; D009929:Organ Size; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood
D000911:Antibodies, Monoclonal; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D012083:Renin