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AMP‐activated protein kinase (AMPK) mediated relaxation is enhanced in aorta from old versus young Sprague‐Dawley Rats
Author(s) -
Ford Rebecca J,
Durham Kristina,
Rush James WE
Publication year - 2010
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.24.1_supplement.lb546
Subject(s) - ampk , phenylephrine , electrical impedance myography , endocrinology , medicine , aorta , chemistry , vasodilation , endothelium , nitric oxide , relaxation (psychology) , protein kinase a , kinase , biochemistry , blood pressure
Activation of AMPK induces vasorelaxation in young, healthy arteries, but it is unknown if this response is intact in arteries from old animals. Here we investigate AMPK‐mediated relaxation in aorta from aged rats. Relaxation dose‐response curves to the AMPK activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR) were generated in phenylephrine pre‐contracted aortic rings from 12 young (10 wks) and 12 old (85 wks) male Sprague Dawley rats using vascular myography. Area under the dose‐response curves (AUC, arbitrary units) was determined as an index of relaxation. Mechanisms of relaxation were dissected in rings with intact (E+) or mechanically disrupted (E‐) endothelium and with or without pharmacological inhibition of nitric oxide synthase (using N‐nitro‐L‐arginine methyl ester; L‐NAME). Endothelium‐dependent and ‐independent relaxation to AICAR occurred in aortic rings from old (AUC E+: 196±27, E‐: 130±9) and young (AUC E+: 94±5, E‐: 53±4) rats, and responses were enhanced in old versus young rings (P < 0.01 E+, P < 0.01 E‐). In both young and old aorta, the endothelium‐dependent component of relaxation was removed with L‐NAME (AUC OLD: 98±10 P =NS, Young: 52±3 P = NS vs E‐). We demonstrate for the first time that AMPK‐mediated relaxation occurs and is enhanced in aorta from old animals, and that AMPK may be a target to enhance vasomotor function in aged arteries. Funded by NSERC