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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/H679    most recent 01053.2007v2 01053.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tang, X. Articles by Campbell, W. B. PubMed PubMed Citation Articles by Tang, X. Articles by Campbell, W. B.

Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in rabbit aorta

¹Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin; and ²Department of Biochemistry, Humboldt University, Berlin, Germany

Submitted 11 September 2007 ; accepted in final form 22 November 2007

Rabbit 15-lipoxygenase-1 (15-LO-1) oxygenates arachidonic acid (AA) into 15-hydroperoxyeicosatetraenoic acid, which is then converted to the vasodilatory 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA). We studied the age-dependent expression of the 15-LO-1 in rabbit aorta and its effects on the synthesis of THETA, HEETA, and vasoactivity. Aortas of 1-wk-old rabbits express greater amounts of 15-LO-1 mRNA and protein compared with aortas of 4-, 8-, or 16-wk-old rabbits. The synthesis of THETA and HEETA in the rabbit aorta was also reduced with age. THETA synthesis was maximal in 1-wk-old aortas but decreased in aortas of 4- (42%), 8- (4%), and 16-wk-old (1%) rabbits. Similarly, THETA and HEETA synthesis decreased with age in mesenteric arteries from 1-, 4-, 8-, and 16-wk-old rabbits. The maximum vasorelaxation response to acetylcholine (10^–6 M) in the presence of indomethacin and nitro-L-arginine decreased in the order of 1 wk (64.5 ± 6.9%), 4 wk (52.6 ± 8.9%), 8 wk (53.0 ± 9.4%), and 16 wk (33.3 ± 6.6%). Similarly, the maximum relaxation to AA (3 x 10^–4 M) decreased with age in the order of 1 wk (60.4 ± 8.9%), 4 wk (56.3 ± 5.8%), 8 wk (41.8 ± 12.3%), and 16 wk (28.9 ± 1.6%). In contrast, the vasorelaxation to sodium nitroprusside was not significantly altered by age. These data indicate that aortic 15-LO-1 expression and activity are downregulated with aging in rabbits. This decrease is paralleled by the reduced synthesis of vasoactive THETA and HEETA and aortic relaxations to acetylcholine and AA.

endothelium-derived hyperpolarizing factor; arachidonic acid; acetylcholine; vasodilation