title: Imperatorin prevents cardiac hypertrophy and the transition to heart failure via NO-dependent mechanisms in mice.
abstract: Augmented endothelial nitric oxide (NO) synthase (eNOS) signaling has been reported to be associated with improvements in cardiac remodeling, and NO levels have been shown to be related to cardiac hypertrophy and heart failure. Imperatorin, a dietary furanocoumarin, has been shown to prevent cardiac hypertrophy in the spontaneous hypertension rats (SHR). Thus, we aimed to clarify whether imperatorin attenuates both cardiac hypertrophy and heart failure via the NO-signaling pathway. In neonatal mouse cardiac myocytes, imperatorin inhibited protein synthesis stimulated by either isoproterenol or phenylephrine, which was unchanged by NG-nitro-L-arginine methyl ester (L-NAME). Four weeks after transverse aortic constriction (TAC) on Kunming (KM) male mice, the ratio of heart weight to body weight was lower after imperatorin treatment than in controls (6.60 ± 0.35 mg/g in TAC, 4.54 ± 0.29 mg/g with imperatorin 15 mg kg(-1)d(-1), ig, P<0.01); similar changes in the ratio of lung weight to body weight (7.30 ± 0.85 mg/g in TAC, 5.42 ± 0.51 mg/g with imperatorin 15 mg kg(-1)d(-1), ig) and the myocardial fibrosis. All of these improvements were blunted by L-NAME. Imperatorin treatment significantly activated phosphorylation of eNOS. Myocardial mRNA levels of natriuretic peptide precursor type B and protein inhibitor of NO synthase, which were increased in the TAC mice, were decreased in the imperatorin-treated ones. Imperatorin can attenuate cardiac hypertrophy both in vivo and in vitro, and halt the process leading from hypertrophy to heart failure by a NO-mediated pathway.
authors: School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
authors: Yan
authors: Y
authors: Zhang
authors: Yanjun
authors: Y
authors: Cao
authors: Haijie
authors: H
authors: Duan
authors: Hongying
authors: H
authors: Wang
authors: LangChong
authors: L
authors: He
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000517:prevention & control*; D002478:Cells, Cultured; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism; D011564:Furocoumarins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000517:prevention & control*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism
chemical_list: D011564:Furocoumarins; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D052250:Nitric Oxide Synthase Type III; C486069:Dynll1 protein, rat; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D056445:Cytoplasmic Dyneins; C031534:imperatorin