Aging impairs endothelium-dependent NO-mediated dilatation, which results from increased production of reactive oxygen species (ROS). The local generation of angiotensin II (ANGII) is increased in aging arteries and contributes to inflammatory and fibrotic activity of smooth muscle cells and arterial wall remodeling. Although prolonged in vivo ANGII inhibition improves the impaired endothelial dilatation of aging arteries, it is unclear whether this reflects inhibition of intravascular or systemic ANGII systems. Experiments were therefore performed on isolated tail arteries from young (3-4 months) and old (22-24 months) F344 rats to determine if a local renin-angiotensin system contributes to the endothelial dilator dysfunction of aging. Aging impaired dilatation to the endothelial agonist, acetylcholine, but did not influence responses to a NO donor (DEA NONOate). Dilatation to acetylcholine was greatly reduced by NO synthase inhibition (LNAME) in young and old arteries. In isolated arteries, acute inhibition of angiotensin converting enzyme (ACE) (perindoprilat), renin (aliskiren) or AT1 receptors (valsartan, losartan) did not influence dilatation to acetylcholine in young arteries, but increased responses in old arteries. After ANGII inhibition, dilator response to acetylcholine were similar in young and old arteries. ROS activity, which was increased in endothelium of aging arteries, was also reduced by inhibiting ANGII (perindoprilat, losartan). Renin expression was increased by 5.6 fold and immunofluorescent levels of ANGII were confirmed to be increased in aging compared to young arteries. Exogenous ANGII inhibited acetylcholine-induced dilatation. Therefore, aging-induced impairment of endothelium-dependent dilatation in aging is caused by a local intravascular renin-angiotensin system.
- Angiotensin II
- AT1 Receptors
- Copyright © 2016, American Journal of Physiology - Heart and Circulatory Physiology