We hypothesized that aging is characterized by a reduced release of nitric oxide (NO) in response to shear stress in resistance vessels. Mesenteric arterioles and arteries of young (6 mo) and aged (24 mo) male Fischer 344 rats were isolated and cannulated. Shear stress (15 dyn/cm 2 )-induced dilation was significantly reduced and shear stress (1, 5, 10, and 15 dyn/cm 2 )-induced increases in perfusate nitrite were significantly smaller at all shear stress levels in vessels of aged rats. Inhibition of NO synthesis abolished shear stress-induced release of nitrite. Furthermore, shear stress (15 dyn/cm 2 )-induced release of nitrate was significantly higher and total nitrite (nitrite plus nitrate) was significantly lower in vessels of aged rats. Tiron or SOD significantly increased nitrite released from vessels of aged rats, but this was still significantly less than that in young rats. Superoxide production was increased and the activity of SOD was decreased in vessels of aged rats. There were no differences in endothelial NO synthase (eNOS) protein and basal activity or in Cu/Zn-SOD and Mn-SOD proteins in vessels of the two groups, but extracellular SOD was significantly reduced in vessels of aged rats. Maximal release of NO induced by shear stress plus ACh (10 −5 M) was comparable in the two groups, but phospho-eNOS in response to shear stress (15 dyn/cm 2 ) was significantly reduced in vessels of aged rats. These data suggest that an increased production of superoxide, a reduced activity of SOD, and an impaired shear stressinduced activation of eNOS are the causes of the decreased shear stress-induced release of NO in vessels of aged rats. Keywords endothelium; superoxide; superoxide dismutase Age-related endothelial dysfunction has been characterized by reduced agonist-induced vasodilatation (33). In addition, several studies showed that flow-induced dilation, the most physiologically relevant measure of endothelium-dependent regulation of vascular tone, was reduced in healthy elderly humans and aged animals (4,7,25,36) and that the sensitivity of arteriolar endothelium to fluid shear stress is decreased with advancing age (31). The
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.