Chronic high blood flow potentiates shear stress-induced release of NO in arteries of aged rats.
Aging impairs shear-stress-dependent dilation of arteries via increased superoxide production, decreased SOD activity, and decreased activation of endothelial nitric oxide (NO) synthase (eNOS). In the present study, we investigated whether chronic increases in shear stress, elicited by increases in blood flow, would improve vascular endothelial function of aged rats. To this end, second-order mesenteric arteries of young (6 mo) and aged (24 mo) male Fischer-344 rats were selectively ligated for 3 wk to elevate blood flow in a first-order artery [high blood flow (HF)]. An in vitro study was then conducted on first-order arteries with HF and normal blood flow (NF) to assess shear stress (1, 10, and 20 dyn/cm(2))-induced release of NO into the perfusate. In HF arteries of both age groups, shear stress-induced NO production increased significantly. In 24-mo-old rats, the reduced shear stress-induced NO production in NF arteries was normalized by HF to a level similar to that in NF arteries of 6-mo-old rats. The increased NO production in HF arteries of 24-mo-old rats was associated with increased shear stress-induced dilation, expression of eNOS protein, and shear stress-induced eNOS phosphorylation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, reduced shear stress-induced eNOS phosphorylation and vasodilation. Superoxide production decreased significantly in HF compared with NF arteries in 24-mo-old rats. The decreased superoxide production was associated with significant increases in CuZn-SOD and extracellular SOD protein expressions and total SOD activity. These results suggest that stimulation with chronic HF restores shear-stress-induced activation of eNOS and antioxidant ability in aged arteries.
Yan
Changdong
C
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Huang
An
A
Kaley
Gabor
G
Sun
Dong
D
D000375:Aging / Q000502:physiology*; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D004548:Elasticity; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D033081:Shear Strength; D013314:Stress, Mechanical
D009569:Nitric Oxide