Effects of intravenous administration of prostacyclin on regional blood circulation in awake rats

Raczka, Ewa; Quintana, Antonio García

doi:10.1038/sj.bjp.0702426

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…Similar to the upper GI tract, an important mechanism for the onset of NSAIDs-induced small intestinal damage is the inhibition of COXs. Since PGs also play a crucial role in the maintenance of intestinal integrity by upregulating mucosal blood flow and mucus/fluid and regulating intestinal motility [53][54][55], PG deficiency subsequent to COX inhibition leads to the impairment of the mucosal defensive system in the small bowel. In an animal study, neither SC-560 (a selective COX-1 inhibitor) nor rofecoxib (a selective COX-2 inhibitor) alone caused intestinal damage, but their combined administration induced lesions.…”

Section: Pathophysiology Of Nsaids-induced Enteropathy Cox Inhibitionmentioning

confidence: 99%

Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

2019

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Recent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal antiinflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-a and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1b into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step. Keywords Non-steroidal anti-inflammatory drug Á Lowdose aspirin Á Enteropathy Á Innate immunity Á Misoprostol Abbreviations NSAID Non-steroidal anti-inflammatory drug RA Rheumatoid arthritis

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Section: Pathophysiology Of Nsaids-induced Enteropathy Cox Inhibitionmentioning

confidence: 99%

Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

2019

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“…Its main action in vivo is to inhibit aggregation and adhesion of platelets (Higgs et al, 1978;Murata et al, 1997). Prostacyclin has vasodilator properties and is suggested to contribute to hypercapnic and hypoxic cerebral hyperemia, but its role in regulation of vascular resistance under normal conditions has not yet been defined (Heinert et al, 1999;McCalden et al, 1984;Raczka and Quintana, 1999). Prostacyclin or its stabile analogues has been shown to increase cerebral blood flow, decrease extravasation of macromolecules and decrease edema formation following cerebral ischemia (Fukuyama et al, 1993;Pluta, 1994;Shima et al, 1995;Terawaki et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

Low-Dose Prostacyclin Improves Cortical Perfusion following Experimental Brain Injury in the Rat

Bentzer

Venturoli²,

Carlsson³

et al. 2003

Journal of Neurotrauma

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It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.

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“…Early studies on PGI 2 indicated a reduction in cerebral blood flow after PGI 2 intravenous infusion in normotensive humans and rats [9–12], implicating a possible role in the maintenance of cerebrovascular tone. This is probably of importance since in cases of brain injury, PGI 2 may potentially be therapeutic.…”

Section: Introductionmentioning

confidence: 99%

Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like behavior

Vollert

Ohia

Akasaka

et al. 2014

Behavioural Brain Research

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Prostacyclin is an endogenous lipid metabolite with properties of vasodilation and anti-platelet aggregation. While the effects of prostacyclin on the vascular protection have been well-documented, the role of this eicosanoid in the central nervous system has not been extensively studied. Recently, a transgenic mouse containing a hybrid enzyme, of cyclooxygenase-1 linked to prostacyclin synthase, was developed that produces elevated levels of prostacyclin in vivo. The goal of this study was to investigate whether increased prostacyclin biosynthesis could affect behavioral phenotypes in mice. Our results uncovered that elevated levels of prostacyclin broadly affect both cognitive and non-cognitive behaviors, including decreased anxiety-like behavior and improved learning in the fear-conditioning memory test. This study demonstrates that prostacyclin plays an important, but previously unrecognized, role in central nervous system function and behavior.

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Effects of intravenous administration of prostacyclin on regional blood circulation in awake rats

Cited by 8 publications

References 51 publications

Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

Low-Dose Prostacyclin Improves Cortical Perfusion following Experimental Brain Injury in the Rat

Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like behavior

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