Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Oct 2002
Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits.
1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo-oxygenase pathway, underlies the diversity of responses of regional kidney perfusion to vasoactive agents, we tested the effects of intravenous indomethacin on responses to renal arterial bolus doses of vasoactive agents in pentobarbitone-anaesthetized rabbits. 2. Total renal blood flow (RBF) and regional kidney perfusion were determined by transit time ultrasound flowmetry and laser-Doppler flowmetry, respectively. 3. ⋯ Our results suggest that vasodilator cyclo-oxygenase products contribute to the maintenance of resting renal vascular tone, particularly in vascular elements controlling medullary perfusion. Cyclo-oxygenase products also appear to mediate endothelin-1- and angiotensin II-induced increases in medullary perfusion. However, regionally specific engagement of cyclo-oxygenase-dependent arachidonic acid metabolism does not appear to contribute to the differential effects of noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin on cortical and medullary perfusion.
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Clin. Exp. Pharmacol. Physiol. · Sep 2002
ReviewSpiders of medical importance in the Asia-Pacific: atracotoxin, latrotoxin and related spider neurotoxins.
1. The spiders of medical importance in the Asia-Pacific region include widow (family Theridiidae) and Australian funnel-web spiders (subfamily Atracinae). In addition, cupboard (family Theridiidae) and Australian mouse spiders (family Actinopodidae) may contain neurotoxins responsible for serious systemic envenomation. ⋯ In particular omega-ACTX define a new insecticide target due to a specific action to block insect voltage-gated Ca2+ channels. Both these ACTX show promise for the development of baculoviral recombinant biopesticides expressing these toxins for the control of insecticide-resistant agricultural pests. In addition, they should provide valuable tools for the pharmacological and structural characterization of insecticide targets.
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Clin. Exp. Pharmacol. Physiol. · Aug 2002
Cardiovascular responses during stimulation of hindlimb skeletal muscle nerves in anaesthetized rats.
1. Cardiovascular responses during static skeletal muscle contraction in anaesthetized rats appear to be contradictory. The present study attempted to explain such variations by stimulating different peripheral nerves supplying the hindlimb skeletal muscles using anaesthetized Sprague-Dawley rats. 2. ⋯ The results demonstrate that static muscle contraction following stimulation of the tibial or sciatic nerve with transected peroneal branch, elicits consistent increases in blood pressure and heart rate. Furthermore, stimulation of the peroneal nerve elicits a depressor response, while stimulation of the intact sciatic nerve evokes variable cardiovascular responses. Overall, anaesthetized rats can be excellent models to study the variable cardiovascular responses during activation of group III and/or group IV muscle afferents.
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Clin. Exp. Pharmacol. Physiol. · Jan 2002
ReviewSalvaging the ischaemic penumbra: more than just reperfusion?
1. The ischaemic penumbra is defined as a moderately hypoperfused region that retains structural integrity but has lost function. In animal models of ischaemic stroke, this region is prone to recurrent anoxic depolarization and will become infarcted if reperfusion does not occur. ⋯ However, neurons within this salvaged region may be still at risk of further delayed neuronal injury. 4. In the present review, we aim to revisit the concept of the ischaemic penumbra and explore the role of selective and delayed neuronal injury in enlargement of the volume of infarction, as well as pathogenic mechanisms of white matter ischaemia. Both animal and human models of cerebral ischaemia imaged using magnetic resonance and positron emission tomography techniques will be discussed.
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Clin. Exp. Pharmacol. Physiol. · Nov 2001
ReviewAdenoviral vector-mediated delivery of glial cell line-derived neurotrophic factor provides neuroprotection in the aged parkinsonian rat.
1. The long-term delivery of neurotrophic factors to specific regions of the central nervous system via gene therapy offers a new strategy for the treatment of neurodegenerative disorders. 2. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) is a potent dopaminergic (DA) trophic factor that ameliorates the behavioural and histological consequences of lesioning DA neurons in rodent and primate models of Parkinson's disease. 3. ⋯ Injection of GDNF vector into either the striatum or the SN provided significant cell protection against 6-OHDA. However, only striatal injection of Ad GDNF protected against the development of behavioural and neurochemical changes that occur in the DA-depleted brain. 7. The results of this study are reviewed here and the behavioural and cellular effects of GDNF gene delivery into striatal versus mesencephalic sites are discussed.