Open AccessAgmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol‐fed rabbits
Author(s) -
ElAwady Mohammed S.,
Suddek Ghada M.
Publication year - 2014
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12204
Subject(s) - agmatine , endocrinology , medicine , sodium nitroprusside , cholesterol , endothelial dysfunction , chemistry , malondialdehyde , nitric oxide , endothelium , nitric oxide synthase , high density lipoprotein , lipoprotein , oxidative stress , biochemistry , enzyme , putrescine
Objectives The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase ( iNOS ), against hypercholesterolemia‐induced lipid profile changes and endothelial dysfunction. Methods Hypercholesterolemia was induced by feeding rabbits with a high‐cholesterol diet ( HCD , 0.5%) for 8 weeks. Another HCD ‐fed group was orally administered agmatine (10 mg / kg /day) during weeks 5 through 8. Serum lipid profile, malondialdehyde ( MDA ), nitric oxide ( NO ) and lactate dehydrogenase ( LDH ) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media ( I/M ) ratio. Key findings HCD induced a significant increase in serum total cholesterol ( TC ), low‐density lipoprotein cholesterol ( LDL ‐ C ), triglycerides and high‐density lipoprotein cholesterol ( HDL ‐ C ). Agmatine administration significantly decreased HCD ‐induced elevations in serum TC and LDL ‐ C , MDA , LDH and NO while significantly increased HDL ‐ C levels. Additionally, agmatine significantly protected against HCD ‐induced attenuation of rabbit aortic endothelium‐dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium‐independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. Conclusions This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia‐induced lipemic‐oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition.