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Short‐term AMPK activation improves vascular endothelial function in old mice by a different mechanism than habitual aerobic exercise
Author(s) -
Lawson Brooke R,
Seals Douglas R,
Magerko Katherine A,
Durrant Jessica R,
Zigler Melanie L,
Donato Anthony J,
Lesniewski Lisa A
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.619.9
Subject(s) - ampk , endocrinology , medicine , bioavailability , chemistry , nitric oxide , sodium nitroprusside , enos , amp activated protein kinase , adenosine , phosphorylation , protein kinase a , nitric oxide synthase , pharmacology , biochemistry
Habitual exercise improves endothelium‐dependent dilation (EDD) in old rodents by increasing nitric oxide (NO) bioavailability. Acute exercise activates adenosine monophosphate protein kinase (AMPK), activating endothelial NO synthase and increasing NO production. We determined if pharmacological AMPK activation by aminoimidazole carboxamide ribonucleotide (AICAR, 0.25 mg/kg/day for 14 days, sq) mimics habitual exercise‐induced improvements in EDD and NO bioavailability. Acetylcholine‐mediated EDD was assessed in carotid arteries of young (Y: 4–6 mo), old (O: 29–31 mo), O voluntary wheel running (O‐VR, 10–14 weeks) and O AICAR treated B6D2F1 mice. AMPK phosphorylation was lower in O vs. Y (0.2±0.1 vs. 1.0±0.2 AUs, P=0.01) and was increased after VR (1.4±0.4 AUs, P<0.05) and AICAR treatment (0.5±0.1 AUs, P<0.05) in old mice. Age‐associated decreases in maximal EDD (Y: 97±1 vs. O: 63±11%, P<0.05) and NO bioavailability (Y: 52±6 vs. O: 27±6%, P<0.005) were restored by VR (Max EDD: 96±2%, P<0.05; NO: 48±8%, P<0.05). Short‐term treatment with AICAR improved EDD (91±4%, P<0.05), but not NO bioavailability (28±4%, P=0.47). Sensitivity (IC 50 ) to the NO donor sodium nitroprusside was not significantly different among Y, O and O‐VR groups (SNP; Y: 5.8E‐9±2.4E‐9; O: 5.3E‐9±2.0E‐9; OVR: 8.9E‐9±2.4E‐9 log M, all P>0.05), but AICAR treatment markedly increased sensitivity to SNP (5.6E‐10±1.5E‐10 log M, P<0.05) in old mice. Unlike habitual exercise, short‐term pharmacological activation of AMPK by AICAR improves EDD in old mice by increasing smooth muscle sensitivity to NO. NIH AG013038, AG033755, AG029337