COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats

Extracellular histones disarrange vasoactive mediators release through a COX‐NOS interaction in human endothelial cells

“…O 2 − are released during COX activity as a consequence of their ability to co‐oxidize substances such as NADPH . In this regard, COX‐2 has been demonstrated to be an important source of vascular O 2 − production under inflammatory conditions . In our study, histone‐treated HUVEC showed an increment in COX‐2 expression, along with an enzymatic activity, in accordance with the increased PGI2 levels observed.…”

Augmented oxidative stress and preserved vasoconstriction induced by hydrogen peroxide in coronary arteries in obesity: role of COX‐2

“…Oxidative stress plays a key role in the vascular and metabolic abnormalities associated with obesity and metabolic syndrome including atherosclerosis, hypertension, insulin resistance and type 2 diabetes, which suggests that it might be an early event rather than a consequence in the pathogenesis of these chronic diseases (Roberts and Sindhu, ). ROS like H 2 O 2 , have been demonstrated to contribute to the impaired vascular tone, augmented vasoconstriction and endothelial dysfunction in the insulin resistant states of hypertension (García‐Redondo et al , , ) and obesity (Muñoz et al , ). The results of the present study demonstrate that cardiac and coronary vascular oxidative stress are associated with preserved H 2 O 2 vasoconstriction in coronary and systemic arteries.…”

“…The lack of enhanced H 2 O 2 contractile responses in arteries from obese rats compared with that reported in hypertension might be ascribed to the experimental model used. At 17–18 weeks OZR, a model of genetic obesity/metabolic syndrome, have not yet developed hypertension despite exhibiting hyperinsulinaemia and systemic endothelial dysfunction (Villalba et al , ; Muñoz et al , ). Moreover, we have recently shown that H 2 O 2 activates stored‐operated Ca 2 + entry not coupled to contraction that was augmented in coronary arteries of OZR (Santiago et al , ), which might explain the higher VSM [Ca 2 + ] i mobilization but preserved coronary vasoconstriction found for H 2 O 2 in obese rats.…”

“…Selective inhibition of COX‐2 induced a marked inhibitory effect on H 2 O 2 ‐stimulated O 2 .‐ production, and reduced the increased ROS generation in arteries from OZR to levels similar to those in controls, thus demonstrating that COX‐2 is partially responsible for the elevated levels of oxidative stress in the coronary arterial wall in obesity. Augmented COX‐2‐dependent ROS production is involved in the impaired endothelium‐dependent relaxations and endothelial dysfunction in patients with essential hypertension (Virdis et al , ), in experimental models of hypertension (Martínez‐Revelles et al , ; Tian et al , ) and diabetes (Shi and Vanhoutte, ), and also in renal arteries from insulin resistant OZR (Muñoz et al, ). Endothelial function is initially preserved in the 17–18 months old OZR used in the present study (Villalba et al , ; Contreras et al , ; Climent et al , ).…”

“…Therefore, the aim of the present study was to determine whether obesity might exacerbate H 2 O 2 ‐induced coronary vasoconstriction and impair the signalling pathways of the peroxide‐elicited contractions involving COX signalling and O 2 .‐ generation (Santiago et al , ) in coronary arteries from the OZR. A role for COX‐2, recently involved in the increased vascular oxidative stress and endothelial dysfunction in hypertension (Tian et al , ; Virdis et al , ) and obesity (Muñoz et al , ), will specifically be assessed in coronary arteries from the OZR, a well‐established genetic model of obesity/insulin resistance caused by a dysfunctional gene of the leptin receptor.…”