Urinary thromboxane B2 and prostaglandin E2 in the hepatorenal syndrome: Evidence for increased vasoconstrictor and decreased vasodilator factors

The selective cyclooxygenase-2 inhibitor celecoxib modulates the formation of vasoconstrictor eicosanoids and activates PPARγ. Influence of albumin

“…For instance, it is well established that renal function in cirrhosis depends upon a critical equilibrium between the activity of endogenous vasoconstrictor systems and the renal production of vasodilator PGs. Given that celecoxib, in addition to inhibiting PGs also reduces the formation of 8-isoprostanes, TXB 2 and 12-HETE, which are potent renal vasoconstrictors [14,[42][43][44], this selective COX-2 inhibitor is expected, in theory, to produce less renal side effects than conventional NSAIDs. In fact, a recent double-blind, randomized, placebo-controlled study in patients with cirrhosis and ascites has shown that celecoxib does not impair renal function to a similar extent than the NSAID, naproxen [45].…”

Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis

“…Thus, the role of endothelin in the pathogenesis of HRS needs further investigation. Other studies in patients with cirrhosis and ascites have reported an increase in intrarenal release of other very potent vasoconstrictors, such as 20-HETE and leukotrienes [53][54][55][56].…”

Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome

“…Administration of COX inhibitors to patients with ascites often leads to further disruption of the renal circulatory balance and development of renal failure typically reversible after discontinuation of these drugs [4]. A deficiency in the production of prostaglandin E 2 and prostacyclin has been suggested in patients with HRS, as the urinary concentrations of these substances are decreased compared with in patients with ascites and preserved renal perfusion [107,108]. Misoprostol is a synthetic prostaglandin E 1 analogue and a few studies have been carried out using this drug [85,109].…”