Evidence for the involvement of the cyclooxygenase-metabolic pathway in diclofenac-induced inhibition of spontaneous contraction of rat portal vein smooth muscle cells

Abstract

The effects of diclofenac, a cyclooxygenase (COX) inhibitor, were investigated on spontaneous phasic contractions of longitudinal preparations of the rat portal vein. Diclofenac produced a concentration-dependent decrease in the amplitude of these spontaneous phasic contractions. Diclofenac (30 µM) decreased the amplitude of the spontaneous phasic increase in the F340/F380 ratio of Fura PE3, an indicator of intracellular Ca 2+ concentration. It also reduced the number of action potentials in each burst discharge without changing the resting membrane potential of longitudinal smooth muscle cells. The extent of the distribution of Lucifer Yellow injected into a smooth muscle cell was decreased in the presence of diclofenac (30 µM). Both AH6809, a prostanoid EP receptor antagonist, and SQ22536, an adenylate cyclase inhibitor, decreased the amplitude of the spontaneous contractions. On the other hand, neither ozagrel, a thromboxane synthase inhibitor, nor SQ29548, a prostanoid TP receptor antagonist, significantly affected spontaneous contractions. These results indicate that diclofenac inhibits the amplitude of spontaneous contractions of the rat portal vein through inhibition of electrical activity, which may be related to an inhibition of the cyclooxygenase pathway.

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction

“…This finding was not considered unusual as a similar effect was evident when rat portal veins were exposed to diclofenac (Shimamura et al, 2005). Although the finding is contradictory to glomerular arterial physiology in mammals, it can be explained by finding of Peredo (2003) who demonstrated that indomethacin decreased mesenteric vasoconstriction by inhibiting contractile PGf 2 α production via cyclo-oxygenase (COX) inhibition (Peredo, 2003).…”

Altered arachidonic acid-mediated responses in the perfused kidney of the streptozotocin-induced diabetic rat

“…Arachidonic acid (AA) is metabolized by the vascular endothelium and smooth muscle cells to a variety of cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 (CYP450) epoxygenase products, and these metabolites exert influences over vascular tone (Sekiguchi et al, 1998;Roman et al, 2000;Roman, 2002;Fleming, 2001;Miyata and Roman, 2005;Shimamura et al, 2005;Vizoili et al, 2005;Imig, 2006). The identity and potential biological activity of some of the relevant AA metabolites remain poorly characterized (structurally and/or biologically).…”

L-Arginine-induced current in portal venous smooth muscle cells

“…Although only a proportion of the smooth muscle cells studied showed a response to L-arginine, the depolarization or inward current induced by Larginine may spread over the tissue via cell-to-cell electrical coupling. In rat portal vein using lucifer yellow, we observed that intercellular communication is present (Shimamura et al, 2005).…”