European journal of pharmacology
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Allergens can induce anaphylactic shock and death due to severe hypotension. Potassium channel blockers (K(+)ATP) such as glyburide (GLY) induce vasoconstriction. The effect of K(+)ATP channel blockers on anaphylactic shock is poorly understood. ⋯ PGE2 increased in G3(-)SG; PGF2 increased in G2-SC and G3(-)SG. Na(+) and Ca(++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduces hypotension and increases survival time in rat anaphylactic shock.
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Hydrogen sulfide may protect multiple organ systems against ischemic-reperfusion injuries. It is unknown if treatment with sodium hydrosulfide (NaHS, a hydrogen sulfide donor) will improve myocardial function and minimize oxidative stress in hypoxic-reoxygenated newborn piglets. Mixed breed piglets (1-5 day, 1.5-2.5 kg) were anesthetized and acutely instrumented for the measurement of systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics and blood gas parameters. ⋯ NaHS had no significant effect on systemic and pulmonary blood pressures, regional blood flows, plasma lactate and troponin I levels. The myocardial glutathionine ratio was reduced in piglets treated with NaHS (vs. controls, P<0.05). Post-resuscitation administration of NaHS improves cardiac function and systemic perfusion and attenuates myocardial oxidative stress in newborn piglets following hypoxia-reoxygenation.
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Enhancement of renal sympathetic nerve activity during renal ischemia and norepinephrine overflow from the kidney after reperfusion play important roles in the development of ischemic acute kidney injury. Recently, we have found that moxonidine, an α2/imidazoline Ι1-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the excitation of renal sympathetic nervous system after reperfusion. In the present study, to clarify the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic acute kidney injury, we investigated the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injection of efaroxan, an α2/Ι1 receptor antagonist, on the moxonidine-exhibited actions. ⋯ The suppressive effect of moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and norepinephrine overflow, and i.c.v. injection of efaroxan did not completely inhibit the moxonidine's effects. These results indicate that moxonidine prevents the ischemic kidney injury by sympathoinhibitory effect probably via α2/Ι1 receptors in central nervous system and by suppressing the norepinephrine overflow through α2/Ι1 receptors on sympathetic nerve endings.
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The protective effect of aliskiren on ischemia-reperfusion (I/R) injury in the heart and brain has been reported. Whether or not this protective effect extends into the alleviation of renal I/R injury is not known. Therefore, we investigated the protective effect of aliskiren in the kidney in this study. ⋯ Pretreatment with aliskiren ameliorated I/R induced renal injury, i.e. reduced SCR and BUN levels, ameliorated renal histopathological changes, and decreased the apoptosis of cells and leukocyte infiltration in kidney. I/R injury also decreased superoxide dismutase (SOD) and glutathione (GSH-reduced form) levels, which were blocked with the aliskiren pretreatment. Aliskiren pretreatment exerts a protective effect on ischemia/reperfusion injury in the kidney, via amelioration of oxidative stress, and reduction in leukocyte infiltration and cellular apoptosis.
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The numerous mediators of pain and inflammation are products of injury-induced gene expression that lead to changes in the nervous system and immune responses. These multiple molecules and mechanisms suggest novel strategies that could be used for analgesic drug development. The present study investigated the possible anti-hyperalgesic effects of anomalin in complete Freund's adjuvant (CFA)-induced acute and chronic inflammatory pain models. ⋯ The release of CFA-induced plasma nitrite and paw tissue hyperalgesic cytokine (TNF-α) was reduced remarkably. In addition, the adenosine 5'-triphosphate (ATP) in plasma and substance P (SP) in paw tissue were markedly suppressed by anomalin. These results demonstrate that anomalin exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of the NF-κB, CREB, and MAPKs/AP-1 signaling pathways.