Gene regulation of brain natriuretic peptide in cardiocyte hypertrophy by alpha1-adrenergic stimulation.
1. We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. The production and secretion of BNP and ANP in the hypertrophied ventricles were markedly augmented, serving as a compensation mechanism against ventricular overload by their natriuretic, diuretic and vasodilatory actions. 2. In the present study, we prepared an in vitro model of cardiocyte hypertrophy using cultured neonatal rat ventricular cardiocytes and alpha1-adrenergic stimulation, and examined the gene expressions of BNP and ANP during the process of cardiocyte hypertrophy. 3. The treatment of cultured ventricular cardiocytes with phenylephrine evoked cardiocyte hypertrophy around 24 h after the treatment, which was characterized by augmented expression of the myosin light chain-2 gene and increase in cell size. 4. In this model of cardiocyte hypertrophy, the steady-state level of BNP mRNA rapidly increased to the maximal level within 1 h after the treatment. In contrast, ANP mRNA began to increase at 3 h, and accumulated during the course of cardiocyte hypertrophy. The secretion of BNP from ventricular cardiocytes was also stimulated more rapidly than the ANP secretion. 5. These results indicate that the gene expression of BNP is distinctly regulated from that of ANP in cardiocyte hypertrophy, and suggest a discrete pathophysiological role of BNP as an 'emergency' cardiac hormone against ventricular overload.
Nakagawa
O
O
Department of Medicine and Clincal Science, Kyoto University Graduate School of Medicine, Japan.
Itoh
H
H
Harada
M
M
Komatsu
Y
Y
Yoshimasa
T
T
Nakao
K
K
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor