Effects of Indomethacin on Cerebral Vasodilator Responses to Arachidonic Acid and Hypercapnia in Newborn Pigs

Leffler, Charles W.; Mirro, R.; Shibata, Masaaki; Parfenova, Helena; Armstead, William M.; Zuckerman, Samuel

doi:10.1203/00006450-199306000-00016

Cited by 31 publications

(9 citation statements)

References 13 publications

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“…This blocking effect of indomethacin on the pial arteriolar dilation responses to arachidonic acid and hypercapnia was lost by 3 h. In our unanesthetized piglets, we also observed a significant drop in CBF (49%) when measured at 10 min after 5 mg indomethacinlkg (i.v.). The CBF remained decreased for at least 2 h but returned to baseline values by 4 h. Therefore, although our piglets were not anesthetized, the effects of indomethacin on CBF in our experiment were similar to those of others (20,21).…”

Section: Discussionsupporting

confidence: 89%

Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

et al. 1994

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Section: Discussionsupporting

confidence: 89%

Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

et al. 1994

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“…This fi nding demonstrates that prostanoids are probably not involved in vasodilatation induced by PCRC. In support of idea, indomethacin inhibits the synthesis of prostaglandins and markedly decreases the vascular relaxation induced by arachidonic acid in sheep isolated coronary artery (Cornish et al, 1983) and in newborn pigs (Leffl er et al, 1993). However, in the present study, indomethacin did not affect PCRC-induced relaxation in endothelium-intact aortic strips.…”

Section: Fig 8 Upper: Influence Of Chaps On Pcrc-induced Inhibitionsupporting

confidence: 74%

Inhibitory Effects of Polyphenol-Rich Fraction Extracted from Rubus coreanum M on Thoracic Aortic Contractility of Spontaneously Hypertensive Rats

Lim¹,

Min²,

Woo³

et al. 2011

Biomolecules and Therapeutics

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Abstractprotection as well as inhibitory activities on xanthine oxidase, pancreatin, α-amylase, and angiotensin converting enzyme (Cho, 2005). Recently, it has been demonstrated that polyphenol compounds (PCRC), isolated from Bokboonja liquor, inhibits the CA secretory responses evoked by cholinergic (both muscarinic and nicotinic) stimulation as well as by direct membrane-depolarization from the isolated perfused adrenal gland of the normotensive rats (Kee and Lim, 2007) and spontaneously hypertensive rats (Yu et al., 2009). It seems that this inhibitory effect of PCRC is exerted by inhibiting both the Ca 2+ infl ux into the rat adrenal medullary chromaffi n cells and the uptake of Ca 2+ into the cytoplasmic calcium store partly through the increased NO production due to the activation of nitric oxide synthase (Kee and Lim, 2007;Yu et al., 2009).Generally, the presence of polyphenolic compounds isOriginal Article

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“…251 It must be emphasized that PACAP exerted a potent protective effect against cerebellar neuronal oxidative stress-induced cell death in a concentration-dependent manner through inhibition of hydrogen peroxide-evoked caspase-3 activation and DNA fragmentation. 264 It must be added that IL-1␤, 265 TNF-␣, 266 AA (plus hypercapnia), 267 and NO (plus hypoxia and opioid release) 268 also induced pial arteriolar dilation, sometimes in a dose-dependent manner (IL-1␤), and likewise through the increased generation of cAMP and/or cGMP. 264 It must be added that IL-1␤, 265 TNF-␣, 266 AA (plus hypercapnia), 267 and NO (plus hypoxia and opioid release) 268 also induced pial arteriolar dilation, sometimes in a dose-dependent manner (IL-1␤), and likewise through the increased generation of cAMP and/or cGMP.…”

Section: Important Role Of Pituitary Adenylate Cyclase-activating Polmentioning

confidence: 99%

Possible Pathomechanisms of Sudden Infant Death Syndrome

Prandota¹

2004

American Journal of Therapeutics

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Chronic hypoxia, viral infections/bacterial toxins, inflammation states, biochemical disorders, and genetic abnormalities are the most likely trigger of sudden infant death syndrome (SIDS). Autopsy studies have shown increased pulmonary density of macrophages and markedly more eosinophils in the lungs accompanied by increased T and B lymphocytes. The elevated levels of immunoglobulins, about 20% more muscle in the pulmonary arteries, increased airway smooth muscle cells, and increased fetal hemoglobin and erythropoietin are evidence of chronic hypoxia before death. Other abnormal findings included mucosal immune stimulation of the tracheal wall, duodenal mucosa, and palatine tonsils, and circulating interferon. Low normal or higher blood levels of cortisol often with petechiae on intrathoracic organs, depleted maternal IgG antibodies to endotoxin core (EndoCAb) and early IgM EndoCAb triggered, partial deletions of the C4 gene, and frequent IL-10-592*A polymorphism in SIDS victims as well as possible hypoxia-induced decreased production of antiinflammatory, antiimmune, and antifibrotic cytokine IL-10, may be responsible for the excessive reactions to otherwise harmless infections. In SIDS infants, during chronic hypoxia and times of infection/inflammation, several proinflammatory cytokines are released in large quantities, sometimes also representing a potential source of tissue damage if their production is not sufficiently well controlled, eg, by pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). These proinflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting metabolism of several endogenous lipophilic substances, such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances. In SIDS victims, chronic hypoxia, TNF-alpha and other inflammatory cytokines, and arachidonic acid (AA) as well as n-3 polyunsaturated fatty acids (FA), stimulated and/or augmented superoxide generation by polymorphonuclear leukocytes, which contributed to tissue damage. Chronic hypoxia, increased amounts of nonheme iron in the liver and adrenals of these infants, enhanced activity of CYP2C9 regarded as the functional source of reactive oxygen species (ROS) in some endothelial cells, and nicotine accumulation in tissues also intensified production of ROS. These increased quantities of proinflammatory cytokines, ROS, AA, and nitric oxide (NO) also resulted in suppression of many CYP450 and other enzymes, eg, phosphoenolpyruvate carboxykinase (PEPCK), an enzyme important in the metabolism of FA during gluconeogenesis and glyceroneogenesis. PEPCK deficit found in SIDS infants (caused also by vitamin A deficiency) and eventually enhanced by PACAP lipolysis of adipocyte triglycerides resulted in an increased FA level in blood because of their impaired reesterification to triacylglycerol in adipocytes. In ...

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Effects of Indomethacin on Cerebral Vasodilator Responses to Arachidonic Acid and Hypercapnia in Newborn Pigs

Cited by 31 publications

References 13 publications

Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

Inhibitory Effects of Polyphenol-Rich Fraction Extracted from Rubus coreanum M on Thoracic Aortic Contractility of Spontaneously Hypertensive Rats

Possible Pathomechanisms of Sudden Infant Death Syndrome

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