title: Resveratrol prevents norepinephrine induced hypertrophy in adult rat cardiomyocytes, by activating NO-AMPK pathway.
abstract: Increased adrenergic drive is a major factor influencing the development of pathological cardiac hypertrophy, a stage which precedes overt heart failure. We examined the effect of resveratrol, a polyphenol (found predominantly in grapes), in preventing norepinephrine induced hypertrophy of adult cardiomyocyte, and the role of nitric oxide (NO) and adenosine monophosphate kinase (AMPK) in the effects of resveratrol. Cardiomyocytes isolated from adult rats were pretreated, or not, with resveratrol and then exposed to norepinephrine for 24h. In other experiments cardiomyocytes were also treated with different pharmacological inhibitors of NO synthase, AMPK and sirtuin for elucidating the signaling pathways underlying the effect of resveratrol. In order to validate the role of these signaling molecules in the in vivo settings, we also examined hearts from resveratrol treated spontaneously hypertensive rats (SHR), a genetic model of essential hypertension. Cardiomyocyte hypertrophy was determined by morphometry and (3)H-phenylalanine incorporation assay. NO levels and AMPK activity were measured using a specific assay kit and western blot analysis respectively. In vitro, resveratrol prevented the norepinephrine-induced increase in cardiomyocytes size and protein synthesis. Pharmacological inhibition of NO-AMPK signaling abolished the anti-hypertrophic action of resveratrol. Consistent with the in vitro findings, the anti-hypertrophic effect of resveratrol in the SHR model was associated with increases in NO and AMPK activity. This study demonstrates that NO-AMPK signaling is linked to the anti-hypertrophic effect of resveratrol in adult cardiomyocytes in vitro, and in the SHR model in vivo.
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada.
authors.forename: Sijo J
authors.initials: SJ
authors.lastname: Thandapilly
authors.forename: Xavier L
authors.initials: XL
authors.lastname: Louis
authors.forename: Tonghua
authors.initials: T
authors.lastname: Yang
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Stringer
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Shetuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wigle
authors.forename: Elissavet
authors.initials: E
authors.lastname: Kardami
authors.forename: Peter
authors.initials: P
authors.lastname: Zahradka
authors.forename: Carla
authors.initials: C
authors.lastname: Taylor
authors.forename: Hope D
authors.initials: HD
authors.lastname: Anderson
authors.forename: Thomas
authors.initials: T
authors.lastname: Netticadan
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D013267:Stilbenes; C516138:dorsomorphin; D009536:Niacinamide; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000263:Adenylate Kinase; D000077185:Resveratrol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine