Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jun 2018
Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats.
The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. ⋯ Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief.
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Clin. Exp. Pharmacol. Physiol. · Jul 2017
Randomized Controlled Trial Comparative StudyCompared effects on cerebral oxygenation of ephedrine vs phenylephrine to treat hypotension during carotid endarterectomy.
While both ephedrine and phenylephrine are currently used to treat hypotension occurring during carotid endarterectomy (CEA) under general anaesthesia, phenylephrine may have deleterious effects on the cerebral watershed, due to its exclusively vasoconstrictive action. In this controlled, double-blind randomised trial, we compared the effects of ephedrine and phenylephrine administered in a standardised algorithm to treat the first hypotensive event occurring since induction of anaesthesia until carotid cross-clamping. The algorithm consisted of 1-to-3 boluses of 6 mg of ephedrine or 50 μg of phenylephrine, after a goal-directed fluid therapy. ⋯ The gain in SctO2 on the lowest value during hypotension was also higher under ephedrine than phenylephrine (6.4% vs 4.3% ipsilateral, 5.1% vs 4% contralateral), but not significantly so. Clinical outcomes were unaffected by the treatment, but S100B protein plasma concentration was higher in the phenylephrine group. To conclude, this pilot trial, focusing on intermediate outcomes, suggests that ephedrine should be preferred to phenylephrine to treat hypotension during CEA.
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Clin. Exp. Pharmacol. Physiol. · Apr 2017
Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early-weaned rats at adulthood.
Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. ⋯ These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities.
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Clin. Exp. Pharmacol. Physiol. · Mar 2017
Isoquercitrin protects against pulmonary hypertension via inhibiting PASMCs proliferation.
Pulmonary vascular remodelling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long-term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative, anti-inflammatory and anti-proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodelling in monocrotaline (MCT) induced PAH. ⋯ IQC downregulated the expression of Cyclin D1 and CDK4 as well as inhibited p27Kip1 degradation. Meanwhile, IQC negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, Akt/GSK3β and ERK1/2. IQC ameliorated MCT-induced pulmonary vascular remodelling via suppressing PASMCs proliferation and blocking PDGF-Rβ signalling pathway.
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Clin. Exp. Pharmacol. Physiol. · Mar 2017
Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by downregulation of the high mobility group box 1-toll-like receptor 4-nuclear factor κB signalling pathway.
Pharmacological preconditioning reduces myocardial infarct size in ischaemia-reperfusion (I-R) injury. Dexmedetomidine, a selective α2 -adrenoceptor agonist, has a proven cardioprotective effect when administered prior to I-R, although the underlying mechanisms for this effect are not fully understood. We evaluated whether dexmedetomidine preconditioning could induce a myocardio-protective effect against I-R injury by inhibiting associated inflammatory processes through downregulation of the high mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4)-nuclear factor κB (NF-κB) signalling pathway. ⋯ Dexmedetomidine preconditioning significantly improved cardiac function (P<.05), downregulated the expression of HMGB1-TLR4-NF-κB, reduced levels of TNF-α and IL-6 in isolated ventricles during I-R injury, and significantly reduced CK and LDH levels in coronary outflow (P<.05). All of these effects were partially reversed by yohimbine (P<.05) or rHMGB1 (P<.05). Dexmedetomidine preconditioning alleviated myocardial I-R injury in rats through inhibition of inflammatory processes associated with downregulation of the HMGB1-TLR4-NF-κB signalling pathway via activation at α2 -adrenergic receptors.