Inhibitory effect of natriuretic peptides on aldosterone synthase gene expression in cultured neonatal rat cardiocytes.
BACKGROUND
Although previously thought to be synthesized solely in adrenal cortex, we have recently showed that aldosterone is also produced in and the expression of CYP11B2 mRNA was induced in the failing or hypertensive human ventricle. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with wide biological effects, including inhibition of renin and aldosterone production. We hypothesized that natriuretic peptides reduce the expression of CYP11B2 mRNA in the heart.


RESULTS
To test this hypothesis, we examined whether endogenous or exogenous natriuretic peptides reduce the expression of CYP11B2 mRNA using real-time reverse transcription-polymerase chain reaction. By using HS 142-1, a functional guanylyl cyclase-A type receptor antagonist, we showed that angiotensin II (AngII) pretreated with HS 142-1 increased CYP11B2 mRNA expression (1.62+/-0.12-fold, HS 142-1+AngII 10(-7) mol/L versus AngII 10(-7) mol/L alone, P<0.0001). The treatment with exogenous (10(-6) mol/L) ANP and BNP reduced CYP11B2 mRNA expression (ANP, P=0.0042; BNP, P=0.0012).


CONCLUSIONS
We showed that endogenous and exogenous natriuretic peptides reduced CYP11B2 mRNA expression in cultured neonatal rat cardiocytes. This may inhibit the cardiac renin-angiotensin-aldosterone system by suppressing the gene expression of CYP11B2 and restraining cardiac hypertrophy and fibrosis.
Ito
Teruhiko
T
Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Yoshimura
Michihiro
M
Nakamura
Shota
S
Nakayama
Masafumi
M
Shimasaki
Yukio
Y
Harada
Eisaku
E
Mizuno
Yuji
Y
Yamamuro
Megumi
M
Harada
Masaki
M
Saito
Yoshihiko
Y
Nakao
Kazuwa
K
Kurihara
Hiroki
H
Yasue
Hirofumi
H
Ogawa
Hisao
H
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
C072551:HS 142-1; D011134:Polysaccharides; D012333:RNA, Messenger; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D019405:Cytochrome P-450 CYP11B2; D006152:Cyclic GMP