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Department of Pharmacology and Toxicology, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912
Behavioral
stress and aging are associated with an increase in vascular disease.
This study determined the mechanisms contributing to changes in
endothelium-dependent relaxation of isolated coronary arteries
(300-350 µm) induced by exposure to 10 days of air-jet stress (2 h/day) in young (3 mo) and old (18 mo) male borderline hypertensive
rats (BHR). Aging, alone, did not alter endothelium-dependent relaxation to acetylcholine (ACh) quantitatively but did alter the
mechanisms contributing to relaxation to ACh, which was largely dependent on nitric oxide synthase (NOS) in vessels from old, but not
young, BHR. Behavioral stress resulted in an enhanced relaxation to ACh
that was dependent on NOS in vessels from young stressed compared with
young control BHR. Conversely, relaxation to ACh was reduced in
coronary arteries from old stressed compared with old control BHR. In
vessels from old control BHR, there was an NOS-independent component of
relaxation mediated by opening of
K+ channels that was absent in
vessels from old stressed BHR. The superoxide anion scavenger, tiron,
partially restored relaxation, and inhibition of cyclooxygenase largely
restored relaxation to ACh in vessels from old stressed BHR. In
summary, the effect of behavioral stress was age dependent. ACh-induced
relaxation of coronary arteries was enhanced in an NOS-dependent manner
in young BHR and was impaired in old BHR due to superoxide anions,
vasoconstrictor cyclooxygenase products, and a loss of
K+ channel-mediated relaxation.
endothelium-derived relaxing factors; nitric oxide synthase; cyclooxygenase
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