title: Vasopressin promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor in neonatal mice.
abstract: [Arg8]-vasopressin (AVP) is an essential hormone for maintaining osmotic homeostasis and is known to be a potent vasoconstrictor that regulates the cardiovascular system. In the present study, cardiomyocytes were isolated from neonatal mice and used to investigate the effects of AVP on cardiac hypertrophy. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that vasopressin V1A receptor mRNA, but not V1B or V2 receptor mRNA, was expressed in primary cultured neonatal mouse cardiomyocytes. By exposing the cultured neonatal cardiomyocytes to AVP for 24 h, cell surface areas were significantly increased, suggesting that AVP could induce cardiomyocyte growth. We then investigated the expression level of the atrial natriuretic peptide (ANP), which is a marker of cardiac hypertrophy. Stimulation with AVP increased the expression of cardiomyocyte ANP mRNA in a dose- and time-dependent manner. Immunocytochemical studies showed that stimulation with AVP significantly increased the expression of the ANP protein as well. Furthermore, AVP administration activated extracellular signal-regulated kinase (ERK)1/2 in cardiomyocytes. The effects of AVP on these parameters were significantly inhibited by a selective vasopressin V1A receptor antagonist, OPC-21268, and were not observed in cardiomyocytes from mice lacking the vasopressin V1A receptor. In vivo cardiac hypertrophy in response to pressure overload was attenuated in vasopressin V1A receptor-deficient (V1AR-KO) mice. Taken together, our data suggest that AVP promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor, which is in part regulated by the pathway of ERK1/2 signaling.
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Hiroyama
authors.forename: Shuyi
authors.initials: S
authors.lastname: Wang
authors.forename: Toshinori
authors.initials: T
authors.lastname: Aoyagi
authors.forename: Ryo
authors.initials: R
authors.lastname: Oikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeo
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D006332:Cardiomegaly / Q000378:metabolism*; D049108:Cell Enlargement; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D014176:Protein Biosynthesis; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D010880:Piperidines; D015363:Quinolones; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C068644:OPC 21268; D009320:Atrial Natriuretic Factor; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases