Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
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J. Physiol. Pharmacol. · Dec 2002
A novel, potent and selective inhibitor of the activity of inducible nitric oxide synthase (GW274150) reduces the organ injury in hemorrhagic shock.
An enhanced formation of nitric oxide (NO) by the inducible NO synthase (iNOS) may contribute to the pathophysiology of hemorrhagic shock. This study investigates the effect of a novel, potent and selective inhibitor of iNOS activity (GW274150) on the circulatory failure and the organ injury and dysfunction associated with hemorrhagic shock in the anesthetised rat. ⋯ Interestingly, GW274150 did not reduce the delayed fall in blood pressure associated with hemorrhagic shock. We propose that an enhanced formation of NO from iNOS contributes to the organ injury and dysfunction in hemorrhagic shock, and that highly selective inhibitors of iNOS activity, such as GW274150, may represent a novel therapeutic approach for the therapy of hemorrhagic shock.
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J. Physiol. Pharmacol. · Mar 2002
Sensory nerves in central and peripheral control of pancreatic integrity by leptin and melatonin.
Central nervous system affects pancreatic secretion of enzymes however, the neural modulation of acute pancreatitis has not been investigated. Leptin and melatonin have been recently reported to affect the inflammatory response of various tissues. The identification of specific receptors for both peptides in the pancreas suggests that leptin and melatonin could contribute to the pancreatic protection against inflammation. ⋯ Leptin (10(-10) - 10(-6) M) but not melatonin (10(-8) - 10(-5) M) significantly stimulated NO release from isolated pancreatic acini. Leptin receptor gene expression in these acini was significantly increased by caerulein and leptin. We conclude that 1/ central or peripheral pretreatment with leptin protects the pancreas against its damage induced by CIP, whereas melatonin exerts its protective effect only when given i.p., but not following its i.c.v. adminstration, 2/ activation of leptin receptor in the pancreatic acini appears to be involved in the beneficial effects of leptin on acute pancreatitis, 3/ the protective effects of leptin involve sensory nerves, CGRP and increased generation of NO whereas melatonin-induced protection of the pancreas depends mainly on the antioxidant local effect of this indole, and scavenging of the radical oxygen species in the pancreatic tissue.
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J. Physiol. Pharmacol. · Aug 2001
Clinical Trial Controlled Clinical TrialHelicobacter pylori (H. pylori) infection in coronary artery disease: influence of H. pylori eradication on coronary artery lumen after percutaneous transluminal coronary angioplasty. The detection of H. pylori specific DNA in human coronary atherosclerotic plaque.
The role of infections in pathogenesis of atherosclerosis has been a point of extensive discussion and research. Chronic infection has been proposed to account for the formation and progression of atherosclerotic plaques. Gastric mucosal damage caused by Helicobacter pylori (H. pylori) involves various bacterial and host-dependent toxic substances that have been recently associated with increased risk of coronary artery disease (CAD). ⋯ 1) There is a significant link between CAD and infection with H. pylori, especially expressing CagA proteins; 2) Patients infected with CagA-positive H. pylori show significantly greater coronary artery lumen loss and arterial re-stenosis after PTCA with stent implantation; 3) H. pylori eradication significantly attenuates the reduction in coronary artery lumen in CAD patients after PTCA possibly due to the elimination of chronic inflammation and the decline in proinflammatory cytokine release and 4) The identification of DNA in atherosclerotic plaques of patients with severe CAD supports the hypothesis that infection with H. pylori (especially CagA positive) may influence the development of atherosclerosis.
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Although paracetamol potently reduces pain and fever, its mechanism of action has so far not been satisfactorily explained. It inhibits both COX-1 and COX-2 weakly in vitro, but reduces prostaglandin synthesis markedly in vivo. In mouse macrophage J774.2 cells, COX-2 induced for 48 hr with high concentrations of NSAIDs is more sensitive to inhibition with paracetamol than endotoxin-induced COX-2. ⋯ Inhibition of the activity of this late-appearing COX-2 with indomethacin or a selective COX-2 inhibitor, delays resolution and the inflammation is prolonged. Cultured lung fibroblasts also express COX-2 activity after stimulation with IL-1beta which is highly sensitive to inhibition with paracetamol. Thus, evidence is accumulating for the existence of a COX-2 variant or a new COX enzyme which can be inhibited with paracetamol.
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J. Physiol. Pharmacol. · Jun 2000
Effect of endothelin-1 receptor antagonist BQ-123 on basilar artery diameter after subarachnoid hemorrhage (SAH) in rats.
Aim of the study was to quantify cerebral vasospasm in rats after subarachnoid hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate the influence of endothelin receptor blocker BQ-123 on basilar artery constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was developed by administration of 100 microl autologic, non-heparinized blood to the CM. The sham subarachnoid hemorrhage was developed by intracisternal administration of 100 microl of artificial cerebrospinal fluid. ⋯ The presence of numerous infiltrations composed of neutrophils and macrophages correlated with advanced vasospasm (index of constriction 5 times lower than in normal), suggesting the role of other factors participating in the late phase of vasospasms after SAH. Administration of BQ-123 in the late phase after SAH caused the dilatation of basilar artery. Following the administration of BQ-123 in the late phase (48 h after SAH) the basilar artery dilated, its wall became thinner, and the number of leukocyte infiltrations in the subarachnoid space decreased compared to the values after SAH alone.