Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Sep 2009
Comparative StudyEffects of 1400W and/or nitroglycerin on renal oxygenation and kidney function during endotoxaemia in anaesthetized rats.
1. The pathogenesis of acute renal failure (ARF) in sepsis is multifactorial. The role of nitric oxide (NO) in septic ARF has been a source of controversy. ⋯ The application of 1400 W+NTG significantly reduced plasma NO(x) levels compared with fluid resuscitation and NTG alone. 4. Neither iNOS inhibition, NO donation nor a combination of both showed beneficial effects on systemic haemodynamics, renal oxygenation and renal function compared with fluid resuscitation alone. Our results question the proposed key role of NO in the pathogenesis of septic ARF in rats.
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Clin. Exp. Pharmacol. Physiol. · Sep 2009
Effects of thoracic epidural anaesthesia on cardiac repolarization.
1. Prolongation of the QT interval is associated with a risk of life-threatening cardiac arrhythmias. In the present study, we examined whether reversible blockade of preganglionic sympathetic fibres of the heart, achieved by thoracic epidural anaesthesia, affects cardiac repolarization and thus confers an anti-arrhythmic effect. 2. ⋯ However, there were no changes in the ECG parameters in Group L. 4. In conclusion, reversible blockade of preganglionic sympathetic fibres to the heart, achieved by thoracic epidural anaesthesia, results in a reduction in QTcb, as well as the TDR. These changes may explain the anti-arrhythmic action seen with central blockade.
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Clin. Exp. Pharmacol. Physiol. · Aug 2009
Formalin-induced increase in P2X(3) receptor expression in dorsal root ganglia: implications for nociception.
1. ATP-gated P2X receptors in nociceptive sensory neurons participate in the transmission of pain signals from the periphery to the spinal cord. The effect of formalin on the expression of P2X(3) receptors in dorsal root ganglia (DRG) was characterized using molecular and immunological approaches and the patch-clamp technique. 2. ⋯ At 24 h after the formalin injection, currents in isolated small and middle-sized DRG neurons were increased by 1 micromol/L alpha,beta-methylene-ATP. These currents were completely inhibited by 1 micromol/L A-317491, a potent and selective P2X(3) receptor antagonist. 4. These data suggest that formalin injection leads to early upregulation of P2X(3) expression in the spinal cord and DRG and that this may be one of the mechanisms giving rise to nociception.
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Clin. Exp. Pharmacol. Physiol. · Aug 2009
Ischaemic post-conditioning protects both adult and aged Sprague-Dawley rat heart from ischaemia-reperfusion injury through the phosphatidylinositol 3-kinase-AKT and glycogen synthase kinase-3beta pathways.
1. Numerous studies have demonstrated that ischaemic post-conditioning (IPoC) protects adult rats from myocardial ischaemia-reperfusion (I/R) injury. Recent evidence suggests compromised cardioprotection by IPoC in aged mice. ⋯ LY294002 abolished the IPoC-induced phosphorylation of Akt and GSK-3beta, as well as the infarct-limiting effect of IPoC in adult and aged rats. In addition, IPoC significantly attenuated plasma concentrations of creatine kinase and lactate dehydrogenase after reperfusion in both adult and aged rats. 4. In conclusion, IPoC, at the onset of reperfusion, reduces myocardial infarct size in both adult and aged rat hearts, potentially through a PI3-K-, Akt- and GSK-3beta-dependent mechanism.
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Clin. Exp. Pharmacol. Physiol. · Jul 2009
Comparative StudyReduced lung water transport rate associated with downregulation of aquaporin-1 and aquaporin-5 in aged mice.
1. The purpose of the present study was to examine lung water transport properties and the expression and regulation of the alveolar endothelial water channel aquaporin (AQP)-1 and the epithelial water channel AQP-5 in aged mouse lung using gene expression analysis and water permeability measurements. 2. In aged (20-24-month-old) mice, AQP-1 and AQP-5 mRNA expression decreased by 55.5 and 50.3%, respectively, compared with that in young (8-10-week-old) mice (P < 0.01). ⋯ The present study provides the first evidence of altered lung water transport associated with downregulation of AQPs in aged lung. Blood glucocorticoid hormone levels are important to maintain normal AQP-1 expression in the lung microvascular endothelium. Corticosteroid-induced AQP-1 upregulation may contribute to the role of corticosteroids in accelerating oedema clearance in aged lung.