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Peripheral Mechanisms (peripheral + mechanism)

Distribution by Scientific Domains

Medical Sciences	83%
Life Sciences	16%

Selected Abstracts

Cardiovascular effects of noradrenaline microinjected into the dorsal periaqueductal gray area of unanaesthetized rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005
Gislaine Garcia Pelosi
Abstract The periaqueductal grey area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, noradrenaline (NA) is also known to be involved in central nervous system cardiovascular regulation. In the present study we report the cardiovascular effects of the microinjection of NA into the dorsal portion of the PAG (dPAG) of unanaesthetized rats and the peripheral mechanism involved in their mediation. Injection of NA in the dPAG of unanaesthetized rats evoked a dose-dependent pressor response accompanied by bradycardia. The magnitude of the pressor responses was higher at more rostral sites in the dPAG and decreased when NA was injected into the caudal portion of the dPAG. The responses to NA were markedly reduced in urethane-anaesthetized rats. The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the vasopressin antagonist dTyr(CH2)5(Me)AVP. The results suggest that activation of noradrenergic receptors within the dPAG can evoke pressor responses, which are mediated by acute vasopressin release. [source]

Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action

NEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2003
J. Fioramonti
Abstract The involvement of neurokinin receptors in visceral nociception is well documented. However, the role and localization of NK3 receptors is not clearly established. This study was designed to determine whether NK3 receptor antagonists crossing (talnetant) or not (SB-235375) the blood,brain barrier reduce the nociceptive response to colo-rectal distension (CRD) and whether NK3 antagonism reduces inflammation- or stress-induced hypersensitivity to rectal distension. Isobaric CRD and isovolumic rectal distensions were performed in rats equipped with intramuscular electrodes to record abdominal muscle contractions. In controls, CRD induced a pressure-related (15,60 mmHg) increase in the number of abdominal contractions. Both talnetant and SB-235375 [50 mg kg,1, per oral (p.o.)], which had no effect on colo-rectal tone, reduced the number of contractions associated with CRDs from 30 to 60 mmHg. Three days after rectal instillation of TNBS, abdominal contractions were increased for rectal distension volume of 0.4 mL. This effect was not modified by talnetant (30 mg kg,1, p.o.). Partial restraint stress increased abdominal contractions at all distension volumes (0,1.2 mL). Talnetant (10 mg kg,1, p.o.) abolished the increase observed for 0.8 and 1.2 mL. These results indicate that peripheral NK3 receptor antagonism reduced nociception associated with CRD and hypersensitivity induced by stress but not inflammation. [source]

CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2007
Daniela Cota
Abstract Insulin resistance, dyslipidaemia and obesity are the major cardiometabolic risk factors contributing to the development of type 2 diabetes and cardiovascular disease (CVD). Owing to the increasing prevalence of obesity, type 2 diabetes, and CVD, new and effective pharmacologic therapies are urgently needed. In this regard, the endogenous cannabinoid system (ECS), a neuromodulatory system involved in the regulation of various aspects of energy balance and eating behaviour through central and peripheral mechanisms, may present the potential to meet this need. In the central nervous system (CNS), cannabinoid type 1 (CB1) receptors and their respective ligands, the endocannabinoids, have a significant role in the modulation of food intake and motivation to consume palatable food. CB1 receptors have also been found in organs involved in the regulation of metabolic homeostasis, such as liver, white adipose tissue, muscle and pancreas. Dysregulation of the ECS has been associated with the development of dyslipidaemia, glucose intolerance, and obesity, and CB1 receptor blockade may have a role in ameliorating these metabolic abnormalities. Thus, pharmacologic options targeting the ECS may provide a novel, effective approach to the prevention and management of CVD, type 2 diabetes and obesity. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Muscle afferent contributions to the cardiovascular response to isometric exercise

EXPERIMENTAL PHYSIOLOGY, Issue 6 2004
James P. Fisher
The cardiovascular response to isometric exercise is governed by both central and peripheral mechanisms. Both metabolic and mechanical stresses on the exercising skeletal muscle produce cardiovascular change, yet it is often overlooked that the afferent signal arising from the muscle can be modified by factors other than exercise intensity. This review discusses research revealing that muscle fibre type, muscle mass and training status are important factors in modifying this peripheral feedback from the active muscles. Studies in both animals and humans have shown that the pressor response resulting from exercise of muscle with a faster contractile character and isomyosin content is greater than that from a muscle of slower contractile character. Athletic groups participating in training programmes that place a high anaerobic load on skeletal muscle groups show attenuated muscle afferent feedback. Similarly, longitudinal studies have shown that specific local muscle training also blunts the pressor response to isometric exercise. Thus it appears that training may decrease the metabolic stimulation of muscle afferents and in some instances chronic exposure to the products of anaerobic metabolism may blunt the sensitivity of the muscle metaboreflex. There may be surprising parallels between the local muscle conditions induced in athletes training for longer sprint events (e.g. 400 m) and by the low-flow conditions in, for example, the muscles of chronic heart failure patients. Whether their similar attenuations in muscle afferent feedback during exercise are due to decreased metabolite accumulation or to a desensitization of the muscle afferents is not yet known. [source]

Autoantibodies to coagulation factors

HAEMOPHILIA, Issue 102 2010
J.-M. R. SAINT-REMY
Summary., Tolerance to autoantigens such as coagulation factors is the result of censoring mechanisms occurring at the level of the thymus and bone marrow for autoreactive T and B cells, respectively. In addition, peripheral mechanisms, both intrinsic and extrinsic further control activation of autoreactive cells that have escaped central deletion. Emergence of autoimmunity can occur from disturbances of these control mechanisms by a number of events, many of which are incompletely understood. Insight into this clinically important field is expected from exploitation of recent animal models. [source]

Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agents

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
A. AKBAR
Summary Background, Although development of visceral pain is an important defensive mechanism, hypersensitivity results in a significant clinical problem and is likely to be one of the major factors involved in the pathogenesis of abdominal and chest pain in functional bowel disorders (FBDs). Understanding of the molecular mechanisms involved in peripheral sensitization of visceral nociceptors has advanced as a result of the experimental studies, especially in animal models, which have led to knowledge and identification of key mediators and receptors. Aim, To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options. Methods, Literature review using Ovid and Pubmed from 1966. Results, There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT3 receptors. Conclusion, It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases. [source]

Contribution of central and peripheral factors to residual fatigue in Guillain,Barré syndrome

MUSCLE AND NERVE, Issue 1 2007
Marcel P.J. Garssen MD
Abstract Many patients with Guillain,Barré syndrome (GBS) suffer from severe residual fatigue that has an uncertain basis. We determined the relative contribution of peripheral and central factors during a 2-min fatiguing sustained maximal voluntary contraction (MVC) in 10 neurologically well-recovered GBS patients and 12 age- and sex-matched healthy controls. Physiological fatigue was defined as the decline of voluntary force during an MVC of the biceps brachii. Relative amounts of peripheral fatigue and central activation failure were determined combining voluntary force and force responses to electrical stimulation. Surface electromyography was used to determine muscle-fiber conduction velocity. During the first minute of sustained MVC, peripheral fatigue developed more slowly in patients than in controls. Central fatigue only occurred in patients. The muscle-fiber conduction velocity was higher in patients. The initial MVC, decrease of MVC, initial force response, and initial central activation failure did not significantly differ between the groups. Although peripheral mechanisms cannot be excluded in the pathogenesis of residual fatigue after GBS, these results suggest that central changes are involved. This study thus provides further insight into the factors contributing to residual fatigue in GBS patients. Muscle Nerve, 2007 [source]

Overactive bladder in diabetes: A peripheral or central mechanism?,

NEUROUROLOGY AND URODYNAMICS, Issue 6 2007
Chiharu Yamaguchi
Abstract Aims To study diabetic cystopathy with reference to overactive bladder (OAB). Methods We retrospectively analyzed diabetic cystopathy in our digitized database that comprised 2300 case records, including data from a lower urinary tract symptoms questionnaire, data from a urodynamic study, and data from neurological examinations. Results Diabetic cystopathy was seen in 4% of cases (84 cases): 58 males, 26 females; mean age, 60.8 years; duration of diabetes, 143.5 months; HbA1C, 7.7 %. In addition to large post-void residual and decreased sensation, OAB, detrusor overactivity (DO), and increased bladder sensation were seen in 55%, 42%, and 14%, respectively. The frequency of DO in patients with increased bladder sensation was 58%. DO increased with age, but not with the duration of diabetes. A brain MRI was performed in 32 cases. The frequency of multiple cerebral infarction (MCI) in patients with DO was 76.5%. The remaining 23.5% of patients with DO had no MCI, and the remaining 42% with increased bladder sensation had no DO. Conclusions OAB commonly occurs in diabetic cystopathy. Both central and peripheral mechanisms are involved, e.g., MCI due to diabetic cerebral vasculopathy for the DO, and, to a lesser extent, peripheral nerve irritation for the DO and increased bladder sensation. Neurourol. Urodynam. 26:807,813, 2007. © 2007 Wiley-Liss, Inc. [source]

Study of peripheral circulation in non-pregnant, pregnant and pre-eclamptic women using applied potential tomography

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2004
Badreldeen AHMED
Abstract Background:, Profound changes are known to occur in the cardiovascular system during pregnancy, involving an increase in cardiac output and a fall in peripheral resistance. In some women these adaptations may be inappropriate and this may result in pregnancy-induced hypertension and pre-eclampsia. Aims and methods:, The aims of the study were to evaluate the relatively new, non-invasive technique of applied potential tomography (APT) in measurements of peripheral blood flow, to study peripheral blood flow in a sample of non-pregnant, pregnant and pre-eclamptic women, and to investigate whether the adaptive changes in the peripheral circulation are different in pre-eclampsia compared with normal pregnancy. Applied potential tomography was used to assess peripheral vascular reactivity, by monitoring fluid distribution in calf muscles during postural change Results:, The APT technique was able to detect peripheral vasoconstriction in response to an increase in intramural pressure brought about by passive lowering of the leg (peripheral mechanisms). The peripheral vasoconstriction response was found to be more prominent in woman with pre-eclampsia. Conclusions:, The presence of a local reflex in the lower limb had been postulated and the effect of this reflex on the peripheral circulation could be detected using APT, regardless of how it was initiated. In normal pregnant women this reflex was diminished when compared to non-pregnant women, which might contribute to the reduction in peripheral vascular resistance seen in normal pregnancy. This reflex was defective in pre-eclampsia and this lack of adaptation may be a local reflex contributing to the raised peripheral resistance, which in turn may be a factor in high blood pressure in pre-eclampsia. [source]

Neural control of the urethra and development of pharmacotherapy for stress urinary incontinence

BJU INTERNATIONAL, Issue 8 2003
M.O. Fraser
SUMMARY This review discusses the control of the urethra by the central nervous system, emphasizing the importance of nervous system control and the role of serotonin and noradrenaline in storage, micturition and sphincter reflexes. The concept of pharmacological neuromodulation and the use of pharmacological therapy as first-line therapy for stress urinary incontinence (SUI) is presented. Coordination between the urinary bladder and urethra is mediated by many reflex pathways organized in the brain and spinal cord. During bladder filling, activation of mechanoreceptor afferent nerves in the bladder wall triggers firing in the cholinergic efferent pathways to the external urethral sphincter and in sympathetic adrenergic pathways to the urethral smooth muscle. These storage reflexes depend on interneuronal circuitry in the spinal cord and are modulated by descending pathways. It would therefore seem that neurotransmission in the central nervous system and periphery may be important in SUI, and moreover that pharmacological agents affecting these neurotransmitter pathways may be used to treat SUI. The central and peripheral mechanisms of action of duloxetine affect serotonin and noradrenaline neurotransmission in ways that may ameliorate the symptoms of SUI. [source]

KETANSERIN-INDUCED BAROREFLEX ENHANCEMENT IN SPONTANEOUSLY HYPERTENSIVE RATS DEPENDS ON CENTRAL 5-HT2A RECEPTORS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007
Fu-Ming Shen
SUMMARY 1Ketanserin may influence baroreflex function by blocking 5-HT2A receptors and/or ,1 -adrenoceptors through central and/or peripheral mechanisms. 2In the present study, we tested the hypothesis that the baroreflex sensitivity (BRS)-enhancing effects of ketanserin are mediated by central 5-HT2A receptors in spontaneously hypertensive rats (SHR). 3Using a conjugate of a monoclonal antibody to the serotonin reuptake transporter (SERT) and the toxin saporin (anti-SERT-SAP), which specifically eliminates the neurons that express SERT, the effects of ketanserin (0.3 and 3.0 mg/kg, i.g.) on BRS, blood pressure (BP), heart period (HP) and blood pressure variability (BPV) were compared between conscious intact SHR and SHR pretreated with anti-SERT-SAP. 4Immunochemistry showed that, 2 weeks after intracerebroventricular injection of the toxin, 5-HT expression was strikingly attenuated in the brain, whereas values of BRS, BPV and BP were similar to those in the sham group. In intact SHR, 0.3 mg/kg ketanserin significantly improved BRS (191% control) and reduced BPV without affecting BP; at 3.0 mg/kg, ketanserin significantly increased BRS (197% control) and decreased BPV and BP. In toxin-pretreated SHR, only the high dose of ketanserin improved BRS (132% control), neither of the ketanserin doses reduced BPV, but both significantly decreased BP. 5We conclude that the BRS-enhancing effects of ketanserin are mediated largely by central 5-HT2A receptors, whereas the antihypertensive effect of ketanserin persists even after destruction of serotonergic neurons in the central nervous system. [source]