L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways.
Polyamines (putrescine, spermidine and spermine) are essential for cell growth and differentiation. Nitric oxide exhibits antihypertrophic functions and inhibits cardiac remodelling. However, the metabolism of polyamines and the potential interactions with nitric oxide in cardiac hypertrophy remain unclear. We randomly divided Wistar rats into four treatment groups: controls, isoproterenol (ISO), ISO and L-arginine, and L-arginine. Isoproterenol (5 mg/kg/day, subcutaneously) and/or L-arginine (800 mg/kg/day, intraperitoneally) was administered once daily for 7 days. The expression of atrial natriuretic peptide mRNA was determined by reverse transcription-polymerase chain reaction, and fibrogenesis of heart was assessed by Van Gieson staining. Polyamines were measured with high-performance liquid chromatography, and plasma nitric oxide content and lactate dehydrogenase (LDH) activity were determined with a spectrophotometer. The expression levels of ornithine decarboxylase, spermidine/spermine N1-acetyltransferase (SSAT), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were analysed by Western blot. Heart-to-body weight ratio, left ventricle-to-body weight ratio, atrial natriuretic peptide mRNA expression, collagen fibres and LDH activity were elevated, both ornithine decarboxylase and SSAT proteins were up-regulated, and total polyamines were increased in the group treated with ISO. Additionally, the expression of iNOS was up-regulated, eNOS was down-regulated, and nitric oxide levels were low. Notably, cotreatment with L-arginine reversed most of these changes except for SSAT expression,which was further up-regulated. We propose that increased polyamines and decreased nitric oxide are involved in cardiac hypertrophy induced by ISO and suggest that L-arginine pre-treatment can attenuate cardiac hypertrophy through the regulation of key enzymes of the polyamine and nitric oxide pathways.
Lin
Yan
Y
Department of Pathophysiology, Harbin Medical University, Harbin, China.
Wang
Li-Na
LN
Xi
Yu-Hui
YH
Li
Hong-Zhu
HZ
Xiao
Feng-Gang
FG
Zhao
Ya-Jun
YJ
Tian
Ye
Y
Yang
Bao-Feng
BF
Xu
Chang-Qing
CQ
D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D015317:Biogenic Polyamines / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D002851:Chromatography, High Pressure Liquid; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000318:Adrenergic beta-Agonists; D015317:Biogenic Polyamines; C472610:atrial natriuretic peptide, rat; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D001120:Arginine; D007545:Isoproterenol