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

Abstract

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.

Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria‐style diet

“…Nevertheless, these results contrast with previous studies in which 10 −5 ‐mol/L indomethacin did not affect the vasorelaxant response produced by 10 −9 –10 −5 ‐mol/L rosuvastatin in aortic rings extracted from rats with a standard diet . The current results also contrast with previous reports suggesting that prostaglandins play an important role in the endothelial dysfunction produced in several experimental models of obesity and metabolic syndrome . One possible explanation for this apparent discrepancy is that a CAF diet may produce crosstalk between the NO and prostaglandin pathways, as reported under certain conditions of inflammation .…”

“…8 The current results also contrast with previous reports suggesting that prostaglandins play an important role in the endothelial dysfunction produced in several experimental models of obesity and metabolic syndrome. [43][44][45] One possible explanation for this apparent discrepancy is that a CAF diet may produce crosstalk between the NO and prostaglandin pathways, as reported under certain conditions of inflammation. [46][47][48] In our model of metabolic syndrome, rosuvastatin enhanced the enzyme expression of eNOS and iNOS and, consequently, the enzyme expression of COX-1 and COX-2.…”

COX-2-Derived Prostanoids and Oxidative Stress Additionally Reduce Endothelium-Mediated Relaxation in Old Type 2 Diabetic Rats

“…Certainly, oxidative stress has been shown to play a major role in the reduction in endothelium-mediated relaxation in diabetes in most vascular territories [54] including the mesenteric vasculature [12], [49]. A similar superoxide effect has been shown in the metabolic syndrome [10], [21], [22], [55], [56]. In the present study the ROS level in mesenteric arteries was analyzed using dihydroethidin (DHE) microfluorography as previously shown [21], [22], [57].…”

Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose

“…Arterial diameter was measured in response to stepwise increase in intraluminal pressure (10 to 125 mmHg) and data recorded using Acqknoledge® (Biopac) [ 41 ]. Pressure was then set at 75 mmHg and arteries were fixed in formaldehyde in order to measure media cross-section area and wall thickness as previously described [ 42 ].…”