Cyclooxygenase-2-derived prostanoids reduce inward arterial remodeling induced by blood flow reduction in old obese Zucker rat mesenteric arteries

Obesity is associated with altered arterial structure and function leading to arterial narrowing in most vascular beds, especially when associated with aging. Nevertheless, mesenteric blood flow remains elevated in obese rats, although the effect of aging remains unknown. We investigated mesenteric artery narrowing following blood flow reduction in vivo in 3- and 12-month-old obese Zucker rats.After 21. days, inward remodeling occurred in low flow (LF) arteries in young and old lean rats and in young obese rats (30% diameter reduction). Diameter did not significantly decrease in old obese rats. Phenylephrine-mediated contraction was reduced by approximately 20% in LF arteries in all groups but in old obese rat arteries in which the decrease reached 80%. LF arteries expressed cyclooxygenase-2 and blood 6-keto-PGF1alpha (prostacyclin metabolite) was elevated in old obese rats. In old obese rats, acute cyclooxygenase-2 blockade restored phenylephrine-mediated contraction in LF arteries and chronic cyclooxygenase-2 blockade restored inward remodeling and contractility to control level.Thus, in old obese rats, cyclooxygenase-2-derived prostacyclin prevented the diameter reduction induced by a chronic decrease in blood flow. This adaptation is in favor of a preserved perfusion of the mesentery by contrast with other vascular territories, possibly amplifying the vascular disorders occurring in obesity.