Clinical and experimental pharmacology & physiology
-
Clin. Exp. Pharmacol. Physiol. · Jan 2005
Effects of post-treatment with low-dose propofol on inflammatory responses to lipopolysaccharide-induced shock in conscious rats.
1. In the present study, we used a low dose of propofol (5 mg/kg per h) to investigate its effects on the pro-inflammatory cytokines (tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10) and changes in nitric oxide (NO) following lipopolysaccharide (LPS) for a period of 12 h in conscious rats. 2. Experiments were designed to induce endotoxin shock by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. ⋯ Lipopolysaccharide also caused a decrease in the white blood cell count and haematocrit. 5. Post-treatment with propofol slightly, but not significantly, affected the LPS-induced systemic hypotension, tachycardia, leukocytopenia and anaemia. 6. These findings suggest that low-dose propofol may be beneficial to the inflammatory change in sepsis.
-
Clin. Exp. Pharmacol. Physiol. · Nov 2004
Captopril reverses the reduced vasodilator response to bradykinin in hypertensive pregnant rats.
1. Pregnancy in rats is characterized by a reduction in arterial pressure that is associated with a decreased response to vasoconstrictors. However, the responses to vasodilators in isolated vessels remain controversial and are not well established in hypertensive pregnant rats. 2. ⋯ The NO-dependent component of the responses seems to be more important in hypertensive rats and pregnancy does not modify this profile. 5. Our results suggest that increased ACE activity may be involved in the pregnancy associated reduction in vasodilator responses to BK in the MAB of hypertensive rats. Pregnancy does not modify the relative contribution of the EDHF and NO to the vasodilator effect of BK.
-
Clin. Exp. Pharmacol. Physiol. · Oct 2004
Differences in the determinants of eplerenone, spironolactone and aldosterone binding to the mineralocorticoid receptor.
The importance of mineralocorticoid receptor (MR) antagonists in the treatment of cardiovascular disease has been emphasised by two recent clinical trials, one using spironolactone and the other using a new selective MR antagonist, namely eplerenone. Eplerenone has a very low affinity for the glucocorticoid receptor (GR). Determinants of binding specificity of eplerenone to the MR were investigated using chimeras created between the ligand-binding domains (LBD) of the MR and the GR. ⋯ Similar results were obtained using another MR antagonist, namely spironolactone. Modelling of eplerenone binding to the MR LBD, based on the GR LBD crystal structure, suggests that amino acids 820-844 affect the overall shape of the ligand-binding pocket and that eplerenone acts as an MR antagonist because it fails to stabilize the active conformation of the receptor. In contrast with results with the MR antagonists eplerenone and spironolactone, amino acids 820-844 are sufficient in themselves to confer high-affinity aldosterone binding to the MR, suggesting that the binding determinants of the two antagonists are similar to each other but differ from those of aldosterone.
-
Clin. Exp. Pharmacol. Physiol. · Jul 2004
Randomized Controlled Trial Comparative Study Clinical TrialDose-response of ropivacaine administered caudally to children undergoing surgical procedures under sedation with midazolam.
1. In a double-blind randomized controlled design, 50 children were allocated to receive bupivacaine 0.25% or ropivacaine 0.25%, 0.32%, 0.40% or 0.50% by caudal block. 2. Caudal block was performed after induction of anaesthesia with 2-5% sevoflurane, atropine 10 microg/kg and midazolam 100-300 microg/kg. ⋯ In children, the duration of analgesia produced by caudal block with ropivacaine may be affected by surgical time. At surgical times of 0.5-1 h, ropivacaine 0.25% produced at least 24 h postoperative analgesia. At similar surgical times, ropivacaine 0.32%, 0.40% and 0.50% produced similar analgesic times to bupivacaine 0.25%.
-
Clin. Exp. Pharmacol. Physiol. · May 2004
ReviewDifferential neural control of glomerular ultrafiltration.
The renal nerves constrict the renal vasculature, causing decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Whether renal haemodynamics are influenced by changes in renal nerve activity within the physiological range is a matter of debate. We have identified two morphologically distinct populations of nerves within the kidney, which are differentially distributed to the renal afferent and efferent arterioles. ⋯ In physiological studies, we demonstrated that differential changes in glomerular capillary pressure occurred in response to graded reflex activation of the renal nerves, compatible with our hypothesis. Thus, sympathetic outflow may be capable of selectively increasing or decreasing glomerular capillary pressure and, hence, GFR by differentially activating separate populations of renal nerves. This has important implications for our understanding of the neural control of body fluid balance in health and disease.