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5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR) alters in vitro vasomotor responses of thoracic aorta rings from spontaneously hypertensive (SHR) and Wistar‐Kyoto (WKY) rats
Author(s) -
Ford Rebecca J,
Rush James W.E
Publication year - 2007
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.21.6.a1230-c
Subject(s) - medicine , endocrinology , vasomotor , phenylephrine , sodium nitroprusside , electrical impedance myography , chemistry , vasodilation , thoracic aorta , nitric oxide , acetylcholine , blood pressure , aorta
AICAR has been shown to reduce systolic blood pressure in hypertensive rats and to activate endothelial nitric oxide synthase in cultured cells. However, the effects of in vitro AICAR treatment on isolated vessel vasomotor function are unknown. Aortic rings were isolated from 16–20wk old male SHR and WKY rats and assessed using myography in order to determine potential vasomotor effects of AICAR. Relaxation to increasing concentrations of acetylcholine (ACh) was abolished in SHR vessels pre‐exposed to AICAR (2mM, 30min pre‐incubation, −AICAR=97±6%, +AICAR=−32±5%, p<0.01) but only partially inhibited in WKY rings (−AICAR=98%±8, +AICAR= 43±11%, p<0.01, strain∗drug p<0.01) at maximum [ACh] (10 −4 M). AICAR produced a right‐ward shift in the dose‐response curve generated with sodium nitroprusside in vessels from both rat strains (logEC 50 for SHR: −AICAR=−9.3, +AICAR=−8.6, p<0.01, WKY: −AICAR=−9.2, +AICAR=−8.0, p<0.01, strain∗drug p=0.05). In other experiments, rings were preconstricted with phenylephrine (10 −7 M) and dilation to acute AICAR (2mM) was determined to be 64±12% (p<0.01) and 27±9% (p<0.01) in SHR and WKY rings respectively. Further work is required to understand the mechanisms by which AICAR directly or indirectly affects the vasomotor function in both SHR and WKY vessels and possible reasons for the strain differences to AICAR. Funded by the Heart and Stroke Foundation of Ontario