Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Oct 2008
Comparative StudyShort-term treatment of stroke-prone spontaneously hypertensive rats with an AT1 receptor blocker protects against hypertensive end-organ damage by prolonged inhibition of the renin-angiotensin system.
The aim of the present study was to investigate the effects of short-term treatment with an AT(1) receptor blocker (ARB) on amelioration of hypertensive end-organ damage in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP were divided into two groups: (i) an ARB-treated group; and (ii) a control group. Candesartan (1 mg/kg per day) was administered orally from 6 to 11 weeks of age. ⋯ In contrast, AT(1) receptor expression in the cerebrum and kidney was higher in the ARB group compared with the control group. These results indicate that short-term treatment of SHRSP with ARB at a young age is effective in preventing cerebral oedema after maturation. Such beneficial effects of ARB may be due, in part, to decreased blood pressure and is likely mainly due to inhibition of total circulating and local renin-angiotensin systems.
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Clin. Exp. Pharmacol. Physiol. · Sep 2008
Comparative Study Clinical TrialEffect of anaesthetic agents on p-wave dispersion on the electrocardiogram: comparison of propofol and desflurane.
Anaesthetics influence cardiac electrical activity by various mechanisms; thus, they may have pro-arrhythmic or anti-arrhythmic actions. Increased P-wave dispersion is associated with a risk of paroxysmal atrial fibrillation. The aim of the present study was to analyse the impact of propofol and desflurane on changes in P wave dispersion, which may reflect the anti-arrhythmic effects of these drugs. ⋯ Significant differences were observed between study groups after 1, 3 and 5 min of anaesthesia, and disappeared after tracheal intubation. Mean and maximal P-wave duration did not change in either group. In conclusion, propofol decreases P-wave dispersion and this seems to be connected with the anti-arrhythmic properties of the drug.
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Clin. Exp. Pharmacol. Physiol. · Sep 2008
Sevoflurane post-conditioning protects against myocardial reperfusion injury by activation of phosphatidylinositol-3-kinase signal transduction.
The mechanisms underlying myocardial protection by sevoflurane post-conditioning are unclear. In the present study, we tested two hypotheses: (i) that sevoflurane post-conditioning produces cardioprotection via a phosphatidylinositol-3-kinase (PI3-K)-dependent pathway; and (ii) combining sevoflurane and ischaemic post-conditioning offers an additional benefit against reperfusion injury. Rat isolated perfused hearts were exposed to 25 min ischaemia followed by 90 min reperfusion. ⋯ Sevoflurane-mediated cardioprotection was abolished or inhibited by 15 micromol/L LY294002. In conclusion, sevoflurane acts during early reperfusion after ischaemia to salvage the myocardium by activating PI3-K. The combination of sevoflurane plus ischaemic post-conditioning does not offer any additional benefit over either intervention alone.
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Clin. Exp. Pharmacol. Physiol. · Sep 2008
Clinical TrialPost-transfusional variation in urinary oxygen tension in surgical patients.
Prior studies have suggested urinary oxygen tension (P(u)O2) as a putative index of renal blood flow (RBF) and tissue oxygenation. In the present study, we collected intraoperative data from eight anaemic, bladder-catheterized patients who received erythrocyte transfusions during various surgical procedures under general anaesthesia. Urinary and arterial blood gas analysis and co-oximetry were performed before and after transfusion, during an interval in which RBF was assumed to be constant. ⋯ Pre- and post-transfusion P(u)O2 was 90 +/- 14 and 108 +/- 20 mmHg, respectively (P = 0.036). 4. These results, although limited, suggest that under conditions of stable haemodynamics, systemic oxygenation and renal function, intraoperative blood transfusion may increase P(u)O2 in anaemic anaesthetized patients. If confirmed by subsequent clinical and laboratory studies, P(u)O2 measurement could become a simple, non-invasive way to monitor renal medullary oxygenation and tissue oxygen availability and help determine whether red blood cells should be transfused.
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Clin. Exp. Pharmacol. Physiol. · Aug 2008
Inhibition of ADP-induced platelet aggregation by clopidogrel is related to CYP2C19 genetic polymorphisms.
1. Clopidogrel is one of the most important antithrombotic drugs but has different efficacies in different populations. The aim of the present study was to evaluate the contribution of CYP2C19 genetic polymorphisms to the inhibition of ADP-induced platelet aggregation by clopidogrel in healthy Chinese volunteers. 2. ⋯ There were significant decrease in 2 and 5 micromol/L ADP-induced platelet aggregation at 4, 24 and 72 h after clopidogrel among the three CYP2C19 genotypes compared with baseline (P < 0.001). The change in 5 micromol/L ADP-induced platelet aggregation in subjects with the CYP2C19*1/CYP2C19*1 genotype was greater than that in subjects with the CYP2C19*2/CYP2C19*2and*3 genotype at 4 h (49.0 +/- 15.5 vs 29.7 +/- 17.4%, respectively; P = 0.029), 24 h (48.7 +/- 20.5 vs 25.0 +/- 17.6%, respectively; P = 0.035) and 72 h (45.5 +/- 15.2 vs 26.5 +/- 15.8%, respectively; P = 0.030) after clopidogrel administration. 4. In conclusion, CYP2C19*2 and CYP2C19*3 genetic polymorphisms reduced clopidogrel inhibition of ADP-induced platelet aggregation, with the degree of inhition dependent on the genetic polymorphism present.