TY - JOUR
T1 - Angiotensin II-induced ventricular hypertrophy and extracellular signal-regulated kinase activation are suppressed in mice overexpressing brain natriuretic peptide in circulation
AU - Takahashi, Nobuki
AU - Saito, Yoshihiko
AU - Kuwahara, Koichiro
AU - Harada, Masaki
AU - Kishimoto, Ichiro
AU - Ogawa, Yoshihiro
AU - Kawakami, Rika
AU - Nakagawa, Yasuaki
AU - Nakanishi, Micio
AU - Nakao, Kazuwa
PY - 2003/10
Y1 - 2003/10
N2 - Atrial and brain (B-type) natriuretic peptides (ANP and BNP, respectively) are known to exert various cardioprotective effects. For instance, knocking out the expression of ANP, BNP, or their receptor, guanylyl cyclase-A, induces cardiac hypertrophy and/or fibrosis. The cardiac effects of elevated circulating natriuretic peptides are less well understood, however. We therefore compared angiotensin (Ang) II-induced cardiac hypertrophy and fibrosis in BNP-transgenic (Tg) mice, in which circulating BNP levels were elevated by increased secretion from the liver, and their non-Tg littermates. Left ventricular expression of Ang II type 1a receptor was similar in BNP-Tg and non-Tg mice, and there was no significant difference in the elevation of blood pressure elicited by chronic infusion or acute injection of Ang II. Nevertheless, cardiac hypertrophy and fibrosis were significantly diminished in BNP-Tg mice chronically infused with Ang II. In addition, ventricular activation of extracellular signal-regulated kinase (ERK) induced by acute injection of Ang II was also diminished in BNP-Tg mice, as was activation of ERK kinase (MEK). Conversely, expression of mitogen-activated protein kinase phosphatase (MKP) was significantly increased in the ventricles of BNP-Tg mice. Based on these findings, we conclude that elevated circulating BNP exerts cardioprotective effects via inhibition of a ventricular ERK pathway. The mechanism responsible for this inhibition likely involves 1) increased ventricular MKP expression and 2) inhibition of transduction mediators situated upstream of ERK.
AB - Atrial and brain (B-type) natriuretic peptides (ANP and BNP, respectively) are known to exert various cardioprotective effects. For instance, knocking out the expression of ANP, BNP, or their receptor, guanylyl cyclase-A, induces cardiac hypertrophy and/or fibrosis. The cardiac effects of elevated circulating natriuretic peptides are less well understood, however. We therefore compared angiotensin (Ang) II-induced cardiac hypertrophy and fibrosis in BNP-transgenic (Tg) mice, in which circulating BNP levels were elevated by increased secretion from the liver, and their non-Tg littermates. Left ventricular expression of Ang II type 1a receptor was similar in BNP-Tg and non-Tg mice, and there was no significant difference in the elevation of blood pressure elicited by chronic infusion or acute injection of Ang II. Nevertheless, cardiac hypertrophy and fibrosis were significantly diminished in BNP-Tg mice chronically infused with Ang II. In addition, ventricular activation of extracellular signal-regulated kinase (ERK) induced by acute injection of Ang II was also diminished in BNP-Tg mice, as was activation of ERK kinase (MEK). Conversely, expression of mitogen-activated protein kinase phosphatase (MKP) was significantly increased in the ventricles of BNP-Tg mice. Based on these findings, we conclude that elevated circulating BNP exerts cardioprotective effects via inhibition of a ventricular ERK pathway. The mechanism responsible for this inhibition likely involves 1) increased ventricular MKP expression and 2) inhibition of transduction mediators situated upstream of ERK.
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U2 - 10.1291/hypres.26.847
DO - 10.1291/hypres.26.847
M3 - Article
C2 - 14621189
AN - SCOPUS:10744221251
VL - 26
SP - 847
EP - 853
JO - Hypertension Research
JF - Hypertension Research
SN - 0916-9636
IS - 10
ER -