Effect of behavioral stress on coronary artery relaxation altered with aging in BHR

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 micrometers) 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.