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Cardiovascular Effects of Adenosine in Hypercholesterolemia
Author(s) -
Teng Bunyen,
Mastafa S. Jamal
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.924.2
Subject(s) - medicine , adenosine , endocrinology , adenosine receptor , hyperlipidemia , agonist , cholesterol , aorta , apolipoprotein b , chemistry , receptor , diabetes mellitus
Coronary heart disease, caused mostly by atherosclerosis, is the leading cause of death in this country and around the world. Elevated plasma cholesterol is one of the major independent risk factors for the development of atherosclerosis. Adenosine is an autocoid that plays a critical role in the control of heart rate and coronary flow (CF). There is very little known about the role adenosine may play in regulating CF in hyperlipidemia. In this study, various concentrations (10 −10 to 10 −6 M) of NECA, a non‐selective adenosine receptor (AR) agonist, were infused into isolated hearts from APOE−/− mice on high fat diet (APOE−/− HFD) and its wild type (WT) on normal diet to identify adenosine‐mediated cardiovascular effects in hypercholesterolemia. The aortic responses to NECA were also investigated in organ bath preparation. The concentration‐response to NECA‐mediated decrease in heart rate (A 1 AR effect) was shifted to the right in APOE−/− HFD when compared to WT; while the effect of NECA in increasing CF was shifted to the left (both A 1 and A2A AR are responsible but have opposite effects). We also found that the responses to acetylcholine in aorta were significantly lower in APOE−/− HFD and NECA‐induced contraction (A 1 AR effect) in APOE−/− HFD was significantly lower compared to WT. Our data suggest that A 1 AR responses were down‐regulated, while A 2A AR responses may be up‐regulated in hyperlipidemia. Supported by HL 027339 and an RDG from WVU‐HSC.