Clinical and experimental pharmacology & physiology
-
Clin. Exp. Pharmacol. Physiol. · Jan 2008
Comparative StudyEffects of dipeptidyl peptidase iv inhibition on arterial blood pressure.
1. The aim of the present study was to determine whether inhibition of dipeptidyl peptidase IV (DPP IV) elevates arterial blood pressure and whether any such effect is dependent on genetic background, the sympathetic nervous system and Y(1) receptors. The rationale behind this study was that: (i) neuropeptide (NP) Y(1-36) and peptide YY(1-36) (PYY(1-36)) are endogenous Y(1) receptor agonists and are metabolised by DPP IV to NPY(3-36) and PYY(3-36), which are not Y(1) but rather selective Y(2) receptor agonists; (ii) Y(1) receptors mediate vasoconstriction, whereas Y(2) receptors have little effect on vascular tone; (iii) vaso-constrictor effect of the Y(1) receptor is enhanced in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats; and (iv) NPY(1-36) is released from sympathetic nerve terminals. 2. ⋯ Unlike the results in genetically hypertensive animals, in normotensive WKY rats pretreated with captopril (30 mg/kg, i.v.; MABP = 81 +/- 4 mmHg; n = 6), or hydralazine (5 mg/kg, i.p.; MABP = 63 +/- 4 mmHg; n = 4) or chlorisondamine (10 mg/kg, s.c.; MABP = 63 +/- 4 mmHg; n = 5), P32/98 did not affect arterial blood pressure. 8. We conclude that, in genetically susceptible animals, inhibition of DPP IV increases arterial blood pressure via Y(1) receptors when elevated blood pressure is reduced with antihypertensive drugs provided that the sympathetic nervous system is functional. The results suggest vigilance because DPP IV inhibitors are used more widely in hypertensive patients treated with antihypertensive drugs.
-
Clin. Exp. Pharmacol. Physiol. · Jan 2008
Hyperoxia confers myocardial protection in mechanically ventilated rats through the generation of free radicals and opening of mitochondrial ATP-sensitive potassium channels.
1. One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia-reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. 2. ⋯ When rats were pretreated either with NAC before hyperoxic ventilation or with K(ATP) channel blockers before ischaemia, myocardial protection was abolished. 4. Hyperoxic mechanical ventilation, prior to ischaemia, reduces myocardial reperfusion injury. This is likely to occur through the induction of oxidative stress, which leads to myocyte mitoKATP channel opening.
-
Clin. Exp. Pharmacol. Physiol. · Jan 2008
Randomized Controlled TrialCombined spinal and epidural anaesthesia with chloroprocaine for hysterectomy.
1. The aim of the present study was to determine the clinical efficacy and safety of chloroprocaine (CP) for gynaecological surgery. 2. One hundred and twenty gynaecological patients scheduled for hysterectomy were divided randomly into four groups: Group A (n = 30), 2.5% CP 1.0 mL; Group B (n = 30), 2.5% CP 1.2 mL; Group C (n = 30), 2.5% CP 1.4 mL; and Group D (n = 30), 2.5% CP 1.6 mL. ⋯ No other adverse events or neurologic deficits were found. 4. The present results suggest that 30-35 mg CP in a total volume of 2.2-2.4 mL used for spinal anaesthesia in hysterectomy is safe and efficient. The combination of spinal and epidural anaesthesia with 2.5% CP can achieve 100% satisfactory anaesthesia for this type of surgery.
-
Clin. Exp. Pharmacol. Physiol. · Jan 2008
Comparative StudyEffects of direct haemoperfusion through fibres immobilizing polymyxin B and nafamostat mesilate on endotoxaemia in conscious Guinea-pigs.
1. Direct haemoperfusion through a network of fibres immobilizing polymyxin B (PMX-B) is used for the treatment of septic shock, but the mechanism underlying its clinical benefits remains unclear. The aims of the present study were to assess the actions of direct haemoperfusion through fibres immobilizing PMX-B (PMX-DHP) on the effects of exogenously administered endotoxin in conscious guinea-pigs and to examine the difference in the effects of heparin compared with nafamostat mesilate (NM) used as an anticoagulant. ⋯ In conscious and unrestrained guinea-pig endotoxaemia model, PMX-DHP significantly improved intestinal paralysis and decreases in blood pressure. These effects were augmented more by NM than by heparin when an anticoagulant was used in the perfusion process. These findings suggest that haemoperfusion using PMX and NM performed in the early stage of endotoxaemia is an effective treatment.
-
Clin. Exp. Pharmacol. Physiol. · Jan 2008
Comparative StudyOral mitemcinal (GM-611), an erythromycin-derived prokinetic, accelerates normal and experimentally delayed gastric emptying in conscious dogs.
1. We examined effects of orally administered mitemcinal, an erythromycin-derived motilin agonist, on gastric emptying and antroduodenal motility in conscious normal dogs and conscious dogs with experimentally delayed gastric emptying. For comparison, we also examined the effects of orally administered cisapride. 2. ⋯ Cisapride (3 mg/kg) restored the indices to roughly prevagotomy levels, but none of the increases was significant. Mitemcinal, at a dose of 0.25 mg/kg, also stimulated antroduodenal motility. 6. Because delayed gastric emptying is the basic characteristic of gastroparesis, the fact that mitemcinal accelerated gastric emptying in dogs with normal and delayed gastric emptying much more robustly than cisapride adds to the evidence that mitemcinal is likely to be useful for the treatment of patients with gastroparesis.