The influence of constitutive cox-2 in smooth muscle tissue on the contractile effect of phenylephrine in the rat abdominal aorta

Abstract

Prostanoids are involved in the phenylephrine-induced contraction of the aorta. Here, we examined whether or not constitutive cyclooxygenase-2 (phosholipases C and A2) is the source of prostanoids in the smooth muscle of the arterial wall of the thoracic and abdominal aorta. Both cyclooxygenase isoforms (COX-1 and COX-2) were expressed in the two aortic segments, but their expression was not altered by phenylephrine, the protein synthesis inhibitor cycloheximide, or the phospholipase A2 inhibitors arachidonyl trifluoromethyl ketone and methyl arachidonyl fluorophosponate. Indomethacin and NS398, which are a non-selective and selective COX-2 inhibitor, respectively, but not SC-560, which is a COX-1-selective inhibitor, inhibited the effect of phenylephrine on the abdominal, but not the thoracic, aorta. Similarly, U73122, which is a phospholipase C inhibitor, and RHC80267, which is a diacylglycerol lipase inhibitor, inhibited the effect of phenylephrine. These findings suggest that prostanoids, which are produced by constitutively active COX-2, influence the contractile response of the abdominal aorta and that the production of arachidonic acid relies on phospholipase C and diacylglycerol lipase.

Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats

“…These results are similar to those described in literature, where indomethacin (a non-selective inhibitor of COX) inhibited the contractile response to phenylephrine only in the abdominal but not the thoracic segment of the aorta. showing a significative inhibition in the abdominal segment but not iin the thoracic, there are similar reports that describes a similar inhibition in the abdominal [1131416]. …”

“…Prostaglandins (PGs) produced by COX-1 and COX-2 play an important role in regulating the contractile effect of phenylephrine in abdominal aorta of young rats [1]. Vascular reactivity to different agonists is influenced by the region in which they are found, the age of the animal, and pathologies that may afflict the organism such as hypertension, diabetes or atherosclerosis [23].…”

“…Connolly et al [10] confirm that inhibitors of COX, such as nimesulide or indomethacin, reduce the vascular response of alpha adrenergic agonists in the thoracic aorta of rats without endothelium, possibly by preventing the formation of vasoconstrictor PGs. However the effect of alpha1-adrenergic agonists on the vascular tone is affected by many factors, including the regional characteristics of the vascular bed [1910], which could be modified by aging or development [2410]. …”