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Biomedical subjects

P G Green

Publications and source records attributed to P G Green.

At least 19 recordsLinked to original sources

Relationships between sediment microbial communities and pollutants in two California salt marshes.

Salt marshes are important ecosystems whose plant and microbial communities can alter terrestrially derived pollutants prior to coastal water discharge. However, knowledge regarding relationships between anthropogenic pollutant levels and salt marsh microbial communities is limited, and salt marshes on the West Coast of the United States are rarely examined. In this study, we investigated the relationships between microbial community composition and 24 pollutants (20 metals and 4 organics) in two California salt marshes. Multivariate ordination techniques were used to assess how bacterial community composition, as determined by terminal restriction fragment length polymorphism and phospholipid fatty acid analyses, was related to pollution. Sea urchin embryo toxicity measurements and plant tissue metabolite profiles were considered two other biometrics of pollution. Spatial effects were strongly manifested across marshes and across channel elevations within marshes. Utilizing partial canonical correspondence analysis, an ordination technique new to microbial ecology, we found that several metals were strongly associated with microbial community composition after accounting for spatial effects. The major patterns in plant metabolite profiles were consistent with patterns across microbial community profiles, but sea urchin embryo assays, which are commonly used to evaluate ecological toxicity, had no identifiable relationships with pollution. Whereas salt marshes are generally dynamic and complex habitats, microbial communities in these marshes appear to be relatively sensitive indicators of toxic pollutants.

Animals↗

Central terminals of nociceptors are targets for nicotine suppression of inflammation.

Spinal intrathecal administration of nicotine inhibits bradykinin-induced plasma extravasation, a component of the inflammatory response, in the knee joint of the rat in a dose-related fashion. Nociceptors contain nicotinic receptors and activation of a nociceptor at its peripheral terminal, by capsaicin, also produces inhibition of inflammation. Therefore the aim of this study was to test the hypothesis that the spinal target for this effect of nicotine is the central terminal of the primary afferent nociceptor. Intrathecal administration of the neurokinin-1 receptor antagonist, (3aR,7aR)-7,7-diphenyl-2-(1-imino-2(2-methoxyphenyl)-ethyl) perhydroisoindol-4-1 hydrochloride or the N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonovaleric acid, both antagonists of the action of primary afferent neurotransmitters, markedly attenuated the inhibition of bradykinin-induced plasma extravasation produced by both intrathecal nicotine and intraplantar capsaicin.Conversely, intrathecal administration of an alpha-adrenoceptor antagonist, phentolamine or an opioid receptor antagonist, naloxone, to block descending antinociceptive controls, which provide inhibitory input to primary afferent nociceptors, enhanced the action of both nicotine and capsaicin. These findings support the hypothesis that the central terminal of the primary afferent nociceptor is a CNS target at which nicotine acts to inhibit inflammation.

Afferent Pathways↗

Upgrading of existing sludge treatment processes for phosphorus management serving a EBPR WWTP.

For a large-scale wastewater treatment plant to comply with phosphorus consents using enhanced biological phosphorus removal processes, its sludge and liquor treatment processes need to be carefully upgraded. In this case study, the wastewater treatment plant of interest has three different types of sludge treated by two different and independent sludge treatment processes. The task of upgrading the sludge treatment systems to serve an EBPR process while satisfying other regulatory and operational constraints in a cost effective way presents an interesting challenge. A range of process options was investigated to include P-rich surplus activated sludge treatment, raw sludge treatment, and sludge liquors treatment. Sludge pre-liming, i.e. to introduce lime slurry into raw liquid sludge before the dewatering stage, was studied in bench-scale and full-scale trials for phosphorus precipitation and pathogen reduction. It was applied to the mixture of surplus activated sludge and imported sludge. The results showed that a complete phosphorus precipitation was achieved at above pH 9 with lime addition of 7% (w/w as calcium hydroxide to sludge dry weight). A satisfactory 2-log pathogen reduction was consistently achieved at above pH 11 with lime addition of 14% (w/w). The process significantly simplified the potential upgrading work for sludge and liquor treatment, compared to other alternatives.

Calcium Compounds↗

Key influential factors for sludge pre-fermentation process design--a case study.

Sewage sludge pre-fermentation process produces readily biodegradable carbon, which is essential for reliable biological phosphorus removal and efficient denitrification. This bench scale study was to develop site-specific design parameters for a sludge fermentation process, and to look into the effects of various influential factors. The key factors investigated induded solids retention time (4-8 days), temperature (9-19 degrees C) and sludge concentrations (0.5%-4% DS). The optimum Volatile Fatty Adds yield was found at a sludge concentration of 1%-1.5% DS. A solid retention time of 4 days at 15-20 degrees C was found to be most cost effective. The fermentation reaction was temperature sensitive, which was found to be inefficient at temperature below 12-15 degrees C. Under the optimum conditions, 80-100 mgVFA g(-1) VSS can be generated from fermentation process, which will result in an increase of 20-24 mg l(-1) in the settled sewage based on average flow. A significant pathogen reduction level was also demonstrated over the fermentation period. Liquid sludge from the small rural wastewater treatment plants is often imported to a regional sludge treatment centre for more advanced treatment to comply with the Regulations. The suitability of this imported sludge for pre-fermentation process was also investigated in this study.

Biodegradation, Environmental↗

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control an ongoing vagus-mediated adjustment in the organism's nociceptive sensitivity.

Adrenal Medulla↗

Role of adrenal medulla in development of sexual dimorphism in inflammation.

Many inflammatory diseases show a female predilection in adults, but not prepubertally. Because sex differences in the inflammatory response in the adult rat are mediated, in part, by sexual dimorphism in adrenal medullary function, we investigated the contribution of the adrenal medulla to the ontogeny of sexual dimorphism in inflammation. Whilst there was no sex difference in the magnitude of the plasma extravasation (PE) induced by the potent inflammatory mediator bradykinin (BK) in prepubertal rats, in adult rats BK-induced PE was markedly greater in males. Also, adult male rats, gonadectomized prior to puberty, had a lower magnitude of BK-induced PE than did adult male controls, whilst adult females gonadectomized prepubertally had higher BK-induced PE than did controls. In rats gonadectomized after puberty, the magnitude of BK-induced PE in adult males was not affected, whilst in females it resulted in significantly higher BK-induced PE, similar to the effect of prepubertal gonadectomy. When tested prepubertally, adrenal denervation increased the magnitude of BK-induced PE in females, but not in males. In contrast, in both males and females tested as adults, but castrated prepubertally, and in gonad-intact adult females, adrenal denervation significantly increased the magnitude of BK-induced PE. Adrenal denervation in prepubertal females given adult levels of 17beta-oestradiol produced a marked enhancement in the denervation-induced increase in magnitude of BK-induced PE compared to females not exposed prematurely to sex hormones. These studies suggest that an adrenal medulla-dependent inhibition of BK-induced PE is present in female but not male rats, and is enhanced by oestrogen but suppressed by testosterone.

Adrenal Medulla↗

Gender and gonadal hormone effects on vagal modulation of tonic nociception.

We studied the influence of gender and gonadal hormones on modulation of tonic nociception exerted by vagal activity. In male rats, subdiaphragmatic vagotomy resulted in significantly reduced nociceptive behavior during phase 2 of the formalin test. Whereas gonadectomy alone had no effect, it completely eliminated the suppressive effect of subdiaphragmatic vagotomy; however, sex hormone replacement with either testosterone or dihydrotestosterone did not restore the ability of subdiaphragmatic vagotomy to suppress nociceptive behavior. These results suggest that, in males, a gonad-dependent but androgenic gonadal hormone-independent mechanism contributes to pronociceptive effects of vagal afferent activity. Although neither gonadectomy nor subdiaphragmatic vagotomy alone affected the response to formalin in females, gonadectomy plus vagotomy resulted in significantly reduced nociceptive behavior during phase 2. Reconstitution with 17 beta-estradiol implants in gonadectomized females not only prevented suppression of nociceptive behavior seen with gonadectomy plus vagotomy, but also led to increased nociceptive behavior in the interphase between phases 1 and 2. However, placement of 17 beta-estradiol implants in gonad-intact females had no effect on formalin-induced nociceptive behavior. The finding that estrogen produced an increase in nociceptive behavior in gonadectomized female rats after vagotomy but not in normal female rats (with intact gonads and subdiaphragmatic vagus) suggests that the interaction between estrogen and nociceptive afferent activity is suppressed by vagal function. In conclusion, a nonandrogenic action of testicular function in male rats and estrogen in females seems to influence the effect of vagal activity on formalin-induced nociceptive behavior.

Journal Article↗

Opioid inhibition of formalin-induced changes in plasma extravasation and local blood flow in rats.

Hindpaw injection of dilute formalin produces brief (Phase 1) and persistent (Phase 2) nociceptive responses in the rat. We recently showed that systemically-administered remifentanil during Phase 1 interacted with peripheral opioid receptors to delay the onset and termination of Phase 2 (Taylor et al., 1997b). To test the hypothesis that opioid inhibition of proinflammatory events during Phase 1 contributed to this delay, we evaluated the effects of remifentanil on the time course of formalin-induced inflammation. We found that formalin increased paw thickness (edema), plasma extravasation and local blood flow within minutes of its injection, i.e. during Phase 1. Each of these responses was blocked during remifentanil administration (30 microg/kg i.v. bolus, followed 90 s later with a 15 microg/kg/min infusion for 13.5 min), indicating that opioids inhibit Phase 1 inflammation. Opioid blockade of the blood flow response could be reversed with a peripherally-acting opioid antagonist, naloxone methiodide, indicating that remifentanil acted upon peripheral opioid receptors. Although the administration of remifentanil during Phase 1 did not reduce the magnitude of inflammatory responses during Phase 2, it did delay the onset and termination of edema during Phase 2. As this corresponds to the effects of remifentanil on nociceptive responses during Phase 2, we suggest that opioid analgesics act upon peripheral sites to inhibit inflammation during Phase 1, leading to a delay in the temporal profile of inflammatory (and likely nociceptive) responses during Phase 2.

Analgesics, Opioid↗

Bradykinin-induced neurogenic migration of neutrophils into the rat knee joint.

This study examined the dependence of neurogenic and non-neurogenic synovial plasma extravasation on neutrophils. Perfusion of bradykinin into the knee joint produced both a rapid increase in the magnitude of plasma extravasation and a significant increase in number of neutrophils in the synovium. Both bradykinin-induced plasma extravasation and neutrophil accumulation were dependent on sympathetic post-ganglionic neuron terminals, since both were blocked in sympathectomized rats. Platelet activating factor, which produces plasma extravasation independent of sympathetic neurons, did not increase the number of neutrophils in the synovium. These findings support the suggestion that bradykinin acts on sympathetic nerve terminals in the knee leading to attraction of neutrophils, which promotes plasma extravasation.

Animals↗

Sex steroid regulation of the inflammatory response: sympathoadrenal dependence in the female rat.

To investigate the role of sex steroids in sex differences in the response of rats to the potent inflammatory mediator bradykinin (BK), we evaluated the effect of sex steroid manipulation on the magnitude of BK-induced synovial plasma extravasation (PE). The magnitude of BK-induced PE is markedly less in females. Ovariectomy of female rats increased BK-induced PE, and administration of 17beta-estradiol to ovariectomized female rats reconstituted the female phenotype. Castration in male rats decreased BK-induced PE, and administration of testosterone or its nonmetabolizable analog dihydrotestosterone reconstituted the male phenotype. The results of these experiments strongly support the role of both male and female sex steroids in sex differences in the inflammatory response. Because the stress axes are sexually dimorphic and are important in the regulation of the inflammatory response, we evaluated the contribution of the hypothalamic-pituitary-adrenal and the sympathoadrenal axes to sex differences in BK-induced PE. Neither hypophysectomy nor inhibition of corticosteroid synthesis affected BK-induced PE in female or male rats. Adrenal denervation in females produced the same magnitude increase in BK-induced PE as adrenalectomy or ovariectomy, suggesting that the adrenal medullary factor(s) in females may account for the female sex steroid effect on BK-induced PE. Furthermore, we have demonstrated that in female but not male rats, estrogen receptor alpha immunoreactivity is present on medullary but not cortical cells in the adrenal gland. These data suggest that regulation of the inflammatory response by female sex steroids is strongly dependent on the sympathoadrenal axis, possibly by its action on estrogen receptors on adrenal medullary cells.

Adrenal Glands↗

A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice.

There is great interest in discovering new targets for pain therapy since current methods of analgesia are often only partially successful. Although protein kinase C (PKC) enhances nociceptor function, it is not known which PKC isozymes contribute. Here, we show that epinephrine-induced mechanical and thermal hyperalgesia and acetic acid-associated hyperalgesia are markedly attenuated in PKCepsilon mutant mice, but baseline nociceptive thresholds are normal. Moreover, epinephrine-, carrageenan-, and nerve growth factor- (NGF-) induced hyperalgesia in normal rats, and epinephrine-induced enhancement of tetrodotoxin-resistant Na+ current (TTX-R I(Na)) in cultured rat dorsal root ganglion (DRG) neurons, are inhibited by a PKCepsilon-selective inhibitor peptide. Our findings indicate that PKCepsilon regulates nociceptor function and suggest that PKCepsilon inhibitors could prove useful in the treatment of pain.

Acetic Acid↗

Painful stimulation suppresses joint inflammation by inducing shedding of L-selectin from neutrophils.

Although the inflammatory response is essential for protecting tissues from injury and infection, unrestrained inflammation can cause chronic inflammatory diseases such as arthritis, colitis and asthma. Physiological mechanisms that downregulate inflammation are poorly understood. Potent control might be achieved by regulating early stages in the inflammatory response, such as accumulation of neutrophils at the site of injury, where these cells release chemical mediators that promote inflammatory processes including plasma extravasation, bacteriocide and proteolysis. To access an inflammatory site, neutrophils must first adhere to the vascular endothelium in a process mediated in part by the leukocyte adhesion molecule L-selectin. This adhesion is prevented when L-selectin is shed from the neutrophil membrane. Although shedding of L-selectin is recognized as a potentially important mechanism for regulating neutrophils, its physiological function has not been demonstrated. Shedding of L-selectin may mediate endogenous downregulation of inflammation by limiting neutrophil accumulation at inflammatory sites. Here we show that activation of nociceptive neurons induces shedding of L-selectin from circulating neutrophils in vivo and that this shedding suppresses an ongoing inflammatory response by inhibiting neutrophil accumulation. These findings indicate a previously unknown mechanism for endogenous feedback control of inflammation. Failure of this mechanism could contribute to the etiology of chronic inflammatory disease.

Animals↗

Endocrine and vagal controls of sympathetically dependent neurogenic inflammation.

Recently the very significant role of the postganglionic sympathetic neuron (PGSN) terminal in the production of neurogenic inflammation has been appreciated. An important model of this sympathetically dependent inflammation is venular plasma extravasation (PE) and neutrophil attraction produced by local intra-articular injection of the potent inflammatory mediator bradykinin (BK). Sympathetic-dependent PE in the synovium has been proposed as a protective mechanism in arthritis. In a recent series of studies, a novel mechanism has been discovered by which activation of primary afferent nociceptors exerts a potent feedback inhibition of PGSN-dependent PE. Activation of nociceptive afferents was shown to be involved in this feedback system. Such a negative feedback control of the acute inflammatory response would have survival value; the inflammatory response, as initiated by a high degree of positive feedback, and the inflammatory process itself when persisting can result in significant tissue injury. If indeed HPA axis activity plays a significant physiological role in the modulation of neurogenic inflammation, then physiological processes that modulate the HPA axis would be expected to influence neurogenic inflammation. A dramatic effect of this kind has been demonstrated, in the rat, for vagal afferent activity. In the presence of subdiaphragmatic (or celiac branch) vagotomy, the potency of nociceptive afferent activity to inhibit sympathetically dependent, BK-induced PE was increased by four orders of magnitude compared to vagus-intact animal. Hypoactivity or hyperactivity of these vagally mediated mechanisms could contribute to diseases characterized by either an inadequate or an exaggerated inflammatory response.

Animals↗

Annexin I is a local mediator in neural-endocrine feedback control of inflammation.

Annexin I is a local mediator in neural-endocrine feedback control of inflammation. J. Neurophysiol. 80: 3120-3126, 1998. Activation of primary afferent nociceptors induces a neural endocrine-mediated inhibition of the inflammatory response via a circuit that includes ascending spinal pathways and activation of the hypothalamic-pituitary adrenal (HPA) axis. This circuit inhibits sympathetic neuron-dependent plasma extravasation (PE) in the rat knee joint produced by bradykinin (BK), but not sympathetic neuron-independent PE produced by platelet activating factor (PAF). Noxious (25 mA) but not non-noxious (2.5 mA) electrical stimulation significantly increased plasma corticosterone concentrations, and intravenous infusion of corticosterone (5 micrograms/min) mimicked inhibition of BK-induced PE produced by noxious stimulation. However, perfusion of corticosterone locally through the knee joint, at doses that do not have a systemic action (i.e., </=1 microM), did not inhibit BK-induced PE. Annexin I (lipocortin-1), a 37-kDa member of a family of phospholipid and calcium binding proteins, can mediate local anti-inflammatory effects of glucocorticoids via a mechanism that is partially dependent on inhibition of phospholipase A2 activity and adhesion and transmigration of polymorphonuclear leukocytes. Because BK-induced PE is dependent on both polymorphonuclear leukocytes and phospholipase A2 activity, we tested the hypothesis that the action of corticosterone to inhibit BK-induced PE is mediated by stimulating the production and release of annexin I. Perfusion of BK (150 nM) through the rat knee joint induces a rapid and sustained increase in PE. Co-perfusion of BK with annexin I (100 ng/ml) through the knee joint mimics the inhibition of BK-induced PE produced by noxious electrical stimulation or by intravenous corticosterone. Co-perfusion of BK with annexin I antibody (LCPS1, 1:60 dilution) prevented the inhibition of BK-induced PE produced by noxious electrical stimulation or intravenous corticosterone adminstration. PAF-induced PE, which is not dependent on polymorphonuclear leukocytes, was not inhibited by local perfusion of annexin I. These data suggest that the inhibitory effect of C-fiber activity on BK-induced PE, acting via an HPA circuit, is mediated by annexin I in the knee joint.

Animals↗

Negative feedback neuroendocrine control of inflammatory response in the rat is dependent on the sympathetic postganglionic neuron.

Negative feedback control of inflammation is mediated by activation of nociceptive afferents that in turn activates the hypothalamic-pituitary-adrenal axis to release corticosteroids. Plasma extravasation (PE) produced by the potent inflammatory mediator, bradykinin (BK), but not that induced by another potent inflammatory mediator, platelet-activating factor (PAF), is inhibited by released corticosterone. Because bradykinin, but not PAF, produces PE by a mechanism that is, in part, dependent on the sympathetic postganglionic neuron (SPGN) terminal, we tested the hypothesis that the negative feedback control of inflammation is dependent on the SPGN terminal in the inflamed tissue. In sympathectomized rats, the residual (i.e., SPGN-independent) PE in the knee joint produced by BK was not inhibited by noxious electrical stimulation. Furthermore, intravenous administration of corticosterone potently inhibited, with a similar time-course, the SPGN-dependent, but not the SPGN-independent, component of BK-induced PE. Neither electrical stimulation nor corticosterone inhibited PAF-induced PE. Finally, corticosterone's actions do not appear to be mediated by release of norepinephrine from the SPGN terminal, because neither the alpha-adrenergic receptor antagonist phentolamine nor the beta2-adrenergic receptor antagonist ICI 118, 551 antagonized the inhibition of BK-induced PE by corticosterone. We conclude that in the rat knee joint, negative feedback control of the inflammatory response is dependent on the presence of the SPGN terminal. Further, our data suggest that a significant component of corticosteroid-induced inhibition of PE produced by inflammatory mediators is SPGN-dependent.

Adrenal Cortex Hormones↗

Inhibition of bradykinin-induced plasma extravasation produced by noxious cutaneous and visceral stimuli and its modulation by vagal activity.

Intrathecally applied nicotine reduces bradykinin-induced plasma extravasation (BK-induced PE) in the rat knee joint. This depression is mediated by the hypothalamo-pituitary-adrenal (HPA) axis and is enhanced by interruption of impulse traffic in afferents of the abdominal vagus nerve. Like intrathecal nicotine, electrical stimulation of unmyelinated cutaneous fibers also depresses BK-induced PE, which is also dependent on an intact HPA axis. In this study, we investigated whether the inhibitory effect of intrathecal nicotine can be mimicked by noxious stimulation of skin and of viscera. Furthermore we determined whether this depression is potentiated after subdiaphragmatic vagotomy. Stimulation of visceral afferents in the peritoneum, by intraperitoneal capsaicin injection, dose-dependently decreased BK-induced PE. The capsaicin dose-response function was shifted by 1.5-2 orders of magnitude to the left after vagotomy. Stimulation of visceral afferents in the urinary bladder by capsaicin also dose-dependently reduced BK-induced PE, which similarly was potentiated after vagotomy. Transcutaneous stimulation of unmyelinated nociceptive afferents from the plantar skin of the paw depressed BK-induced PE. This depression had a threshold of approximately 0.25 Hz and was maximal at a stimulation frequency of approximately 1 Hz. After subdiaphragmatic vagotomy, the stimulus response function shifted to the left and the inhibition was significantly larger than in control, in the range of 0.125-1 Hz stimulation. These results show that noxious stimulation of skin and viscera depressed BK-induced PE and that such depression was potentiated after subdiaphragmatic vagotomy in a manner similar to that of intrathecally applied nicotine. Based on these observations, we hypothesize that intrathecal nicotine depresses BK-induced PE by exciting spinal nociceptive neurons or the central projections of nociceptive primary afferent neurons.

Animals↗

Tachyphylaxis develops to bradykinin-induced plasma extravasation in the rat.

Bradykinin, an inflammatory mediator produced from plasma kallikreins, has potent effects on vascular functions, including increasing plasma extravasation and vasodilation. Attenuation in the response (desensitization to maintained exposure or tachyphylaxis to repeated administration) to bradykinin actions on synovial vasculature, a critical variable with respect to the role of bradykinin in sustained or chronic synovial inflammation, has not been elucidated. In the present study, we determined if tachyphylaxis and desensitization for bradykinin-induced plasma extravasation in the knee joint occur. Bradykinin-induced plasma extravasation into the knee joint cavity was determined spectrophotometrically by measuring the concentration of Evans blue dye extravasation into the joint perfusate. To examine for the development of tachyphylaxis, perfusion of bradykinin (160 ng/ml) was repeated after a 40-min wash with normal saline. Continuous intra-articular perfusion of bradykinin produced an increase in plasma extravasation that remained relatively stable with only a small, approximately 15 percent, decrease over 170 min. On the other hand, the levels of plasma extravasation produced by intermittent perfusion of bradykinin were dramatically lower than that induced by the first exposure (i.e., tachyphylaxis). We conclude that bradykinin-induced plasma extravasation develops marked tachyphylaxis but only minimal desensitization.

Animals↗

Sympathetic-dependence in bradykinin-induced synovial plasma extravasation is dose-related.

While previous studies have implicated a role for sympathetic postganglionic neuron-terminals in bradykinin-induced plasma extravasation, a recent report by Cambridge and Brain [Br. J. Pharmacol., 115 (1995) 641-647] has suggested that it is sympathetic-independent. However, the doses of bradykinin used in these two groups of studies were considerably different. Therefore, in the present study, we characterized the sympathetic-dependence of plasma extravasation at varying doses of bradykinin. By measuring the concentration of Evans blue dye extravasation into the joint perfusate following its intravenous injection, bradykinin-induced plasma extravasation in the knee joint cavity was determined spectrophotometrically. To examine the role of sympathetic postganglionic neuron terminals in mediating bradykinin-induced plasma extravasation, we used surgical ablation of the lumbar sympathetic chain. Intra-articular perfusion of BK dose-dependently increased synovial plasma extravasation. After surgical sympathectomy, the dose-response curve for bradykinin-induced plasma extravasation was significantly shifted to the right. We conclude that at concentrations observed in inflamed tissues (between 10(-8) and 10(-7) M), bradykinin-induced plasma extravasation is largely mediated by sympathetic postganglionic neuron terminals.

Animals↗