Role of cyclooxygenase isoforms in prostacyclin biosynthesis and murine prehepatic portal hypertension

Abstract

Skill NJ, Theodorakis NG, Wang YN, Wu JM, Redmond EM, Sitzmann JV. Role of cyclooxygenase isoforms in prostacyclin biosynthesis and murine prehepatic portal hypertension.

The Molecules: Abnormal Vasculatures in the Splanchnic and Systemic Circulation in Portal Hypertension"

“…These observations suggested that COX-1, not COX-2, would be responsible for the increased vasodilation in the superior mesenteric artery of portal hypertensive rats. However, inhibiting COX-1 only neither decreased PGI 2 levels nor ameliorated the hyperdynaic circulatory syndrome in portal hypertensive mice (Skill, et al 2008). A study using both COX-1-/-and COX-2-/-mice in combination of selective COX-2 (NS398) and COX-1 (SC560) inhibitors, respectively, showed that blockade of both COX-1 and COX-2 ameliorated the hyperdynamic circulatory syndrome in portal hypertensive mice.…”

“…COX-1 is a constitutively expressed form, and COX-2 is an inducible form (Smith, et al 2000;Smith, et al 1996). PGI 2 is an important mediator in the development of experimental and clinical portal hypertension (Hou, et al 1998;Ohta, et al 1995;Skill, et al 2008). Increased COX-1 www.intechopen.com Portal Hypertension -Causes and Complications 6 expression contributed to increased arterial vasodilation in the splanchnic circulation in portal hypertensive rats (Hou, et al 1998).…”

Cyclooxygenase-2 S-nitrosylation in salivary gland acinar cell inflammatory responses to <i>Porphyromonas gingivalis</i>: modulatory effect of ghrelin

“…Clinical and experimental evidence indicate that physiological and pathophysiological implications of NO and PGE 2 depend on the type isozyme system involved in their generation, their subcellular targeting and the local concentration [11][12][13]. Of the three NOS isozymes responsible for NO generation, the two expressed constitutively (cNOS) are membrane bound and Ca 2+ -dependent, and provide precise pulses of NO for a fine modulation of the cellular processes that are of importance to the maintenance of normal physiological functions [8,12,14].…”

“…The conversion of AA to PGE 2 is mediated by two COX isozymes, the constitutive isoform or COX-1 and inducible form or COX-2. The COX-1 is responsible for maintaining the normal physiological prostaglandin production required for housekeeping functions, while the induction of COX-2 expression in response to inflammatory stimulus accounts for up-regulation in PGE 2 production observed in various inflammatory diseases [8,11,13,17].…”

Downregulation of cyclooxygenase-1 is involved in gastric mucosal apoptosis via death signaling in portal hypertensive rats

“…Human studies have shown increased, decreased, or unchanged levels of PGs in the gastric mucosa, whereas animal models of PHT gastropathy generally show a reduction of PGs [9][10][11][12]. Uniformly, however, a reduction in PGs by inhibitors causes increased gastric mucosal damage in both animal models and patients with PHT [11,13,14].…”