Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · May 2014
GABAA receptors are involved in the analgesic effects of morphine microinjected into the central nucleus of the amygdala.
The central nucleus of the amygdala (CeA) has an important role in pain perception and analgesia. Opioid and GABAA receptors, which are both involved in pain modulation, are found in high concentration in the CeA. The present study was designed to examine the interaction of opioidergic and GABAergic systems in the CeA during modulation of acute thermal pain. ⋯ The results revealed that microinjection of morphine into the CeA significantly increased TFL in a dose-dependent manner. Microinjection of bicuculline or muscimol in combination with morphine into the CeA increased and decreased TFL, respectively. It seems that morphine in the CeA facilitates the function of descending inhibitory systems by interacting with the activity of local GABAA receptors.
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Clin. Exp. Pharmacol. Physiol. · Apr 2014
Involvement of purinergic receptors and NOD-like receptor-family protein 3-inflammasome pathway in the adenosine triphosphate-induced cytokine release from macrophages.
Adenosine triphosphate (ATP) has been described as a danger signal activating the NOD-like receptor-family protein 3 (NLRP3)-inflammasome leading to the pro-inflammatory cytokine, interleukin (IL)-1β, release in the lung. The NLRP3-inflammasome pathway has been previously described to be involved in experimental collagen deposition and the development of pulmonary fibrosis. The aim of the present study was to investigate the role of the NLRP3 inflammasome pathway and P2X7 purinergic receptor in the activation of human macrophages in vitro by ATP. ⋯ We observed that P2X7 R antagonists, A-438079 and A-740003, were able to reduce the release of IL-1β, but not of IL-1α and IL-6 from macrophages stimulated by ATPγS or BzATP. The present results showed the involvement of the P2X7 R-NLRP3 inflammasome pathway in the secretion of IL-1β from ATP-stimulated human macrophages, and suggest that P2X7 R were not involved in IL-1α and IL-6 release. This study also points out that repression of the P2X7 R represents a novel potential therapeutic approach to control fibrosis in lung injury.
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Clin. Exp. Pharmacol. Physiol. · Mar 2014
Enalapril attenuates ischaemic brain oedema and protects the blood-brain barrier in rats via an anti-oxidant action.
1. In the present study, we investigated the effects of postischaemic angiotensin-converting enzyme (ACE) inhibition with enalapril on vasogenic oedema formation and blood-brain barrier (BBB) integrity following transient focal cerebral ischaemia in rats. 2. Cerebral ischaemia was induced by 60 min occlusion of the right middle cerebral artery, followed by 24 h reperfusion. ⋯ Enalapril significantly (P < 0.05) decreased EB extravasation into the lesioned hemisphere. Enalapril also augmented anti-oxidant activity in ischaemic brain tissue by increasing GSH concentrations and significantly (P < 0.05) attenuating the increased MDA levels in response to ischaemia. 4. In conclusion, inhibition of ACE with a non-hypotensive dose of enalapril may protect BBB function and attenuate oedema formation via anti-oxidant actions.
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Clin. Exp. Pharmacol. Physiol. · Feb 2014
Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.
Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. ⋯ Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI.
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Clin. Exp. Pharmacol. Physiol. · Jan 2014
ReviewIs there a role for ambulatory blood pressure monitoring in pregnancy?
1. Ambulatory blood pressure monitoring (ABPM) has been used in pregnancy for just over 20 years now and is generally well tolerated. Normal values have been established for different gestations; these are slightly higher than conventional blood pressure (BP) in normal pregnancy, presumably reflecting greater activity during the 24 h of ABPM recordings. 2. ⋯ The best role for ABPM is to determine whether women with office hypertension in early pregnancy have true (usually essential) hypertension or white-coat hypertension. The latter can be managed without antihypertensives and pregnancy outcomes appear good, although possibly with a slightly increased incidence of pre-eclampsia. 6. Women who have had pre-eclampsia are at greater life-time risk for cardiovascular diseases; several years postpartum these women have slightly higher ABPM-measured BP than women who had normal pregnancies and a greater propensity to metabolic syndrome.