Clinical and experimental pharmacology & physiology
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1. Cough is a primary defensive reflex that protects the airways from potentially harmful stimuli. 2. ⋯ Currently available therapeutics are mostly ineffective at suppressing excessive coughing. 4. In the present review, we describe the sensory neural pathways involved in cough, how these pathways may become dysfunctional in airway disease and the most recent advances that have been made in identifying future targets for cough suppression.
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Clin. Exp. Pharmacol. Physiol. · Sep 2007
ReviewSickle cell disease: role of reactive oxygen and nitrogen metabolites.
1. Sickle cell disease (SCD) is an inherited disorder of haemoglobin synthesis that is associated with significant morbidity and mortality due to sequelae of episodic vaso-occlusive events: pain crises and multiorgan damage. The microvascular responses to the initiation, progression and resolution of vaso-occlusive events are consistent with an inflammatory phenotype as suggested by activation of multiple cell types, an oxidatively stressed environment and endothelial cell dysfunction. 2. ⋯ The resultant oxidative stress leads to dysfunction/activation of arteriolar and venular endothelial cells, resulting in impaired vasomotor function and blood cell-endothelial cell adhesion. 3. Changes in substrate and cofactor availability for endothelial cell nitric oxide synthase may underlie reactive oxygen- and nitrogen-induced events that contribute to SCD-induced vasculopathy. 4. The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease.
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Clin. Exp. Pharmacol. Physiol. · Jul 2007
Amlodipine prevents monocrotaline-induced pulmonary arterial hypertension and prolongs survival in rats independent of blood pressure lowering.
1. The present study was designed to examine the role of amlodipine in preventing and reversing monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. 2. Rats were injected with MCT (40 mg/kg, s.c.) and randomly given either 6 mg/kg per day of amlodipine in drinking water or placebo for 3 weeks. ⋯ These effects were associated with marked inhibition of the downregulation of eNOS and improvement of pulmonary vascular endothelial activation, as well as anti-inflammatory, antiproliferative and antifibrotic effects in the lung tissue. However, amlodipine failed to reverse established PAH. This study may provide an insight into therapeutic strategy of amlodipine in PAH.
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Clin. Exp. Pharmacol. Physiol. · May 2007
Optimizing dosage of ketamine and xylazine in murine echocardiography.
1. Ketamine and xylazine (KX) mixture is the most commonly used anaesthetic drug during echocardiography in mice to induce sedation and immobility. Nevertheless, the doses of KX reported in the literature vary substantially with associated significant difference in cardiac function. ⋯ Although in the chronic pressure-overload model LV hypertrophy can be detected accurately in both the anaesthetized or conscious state, systolic dysfunction was masked partially by higher doses of xylazine (2.5 or 10 mg/kg) combined with ketamine at 100 mg/kg. 6. With KX anaesthesia, both the dose of xylazine and the anaesthetic duration are critical in achieving an ideal condition for murine echocardiography. Ketamine at 100 mg/kg alone produces acceptable anaesthesia, stable cardiac function with a minimal depressant effect and is therefore recommended if single-dose anaesthetic is to be used.
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Clin. Exp. Pharmacol. Physiol. · May 2007
CB1 receptor activation in the basolateral amygdala produces antinociception in animal models of acute and tonic nociception.
1. Recent studies have suggested that the basolateral nucleus of the amygdala (BLA) participates in the processing of pain information, especially noxious somatic information. Cannabinoid receptors or CB1 mRNA are expressed more in the BLA than in other nuclei of the amygdala. ⋯ Administration of the CB1 receptor antagonist AM251 (0.55, 5.5, or 55.5 ng/side) alone did not alter the nociceptive thresholds in either test. Bilateral microinjection of the selective CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 1 microg/side) had no effect on the antinociception produced by WIN 55,212-2, suggesting that the antinociceptive actions of WIN 55,212-2 are mediated by CB1 receptors. 4. The findings suggest the existence of a CB1-mediated inhibitory system in the BLA that, when activated, can diminish responsivity to acute and tonic noxious stimuli, but that normally has no tonic effect on the response threshold of these stimuli.