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Tumor necrosis factor stimulation of vagal afferent terminal calcium is blocked by cannabinoids
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Abstracts / Autonomic Neuroscience: Basic and Clinical 163 (2011) 1–133
HCarvD treatment reduced significantly this component (11.13 ± 9.32 mm Hg2 SP, 13.30 ± 8.39 mm Hg2 SLD, 9.67 ± 6.63 mm Hg2 SHD vs. 2.92 ± 3.75 mm Hg2 MIHD; P < 0.05). Neither MI nor Carv treatment altered HF (3.55± 2.47 mm Hg2 SP). MI attenuated (3.74 ± 2.96 SP vs. 0.92 ± 0.76 MIP; P > 0.05) and HCarvD reduced the LF/HF ratio (3.74 ± 2.96 SP, 3.30± 2.84 SLD, 3.37 ± 2.51 SHD vs. 0.49 ± 0.48 MIHD; P < 0.05). Conclusion: LCarvD restores the depressed BPV in rats with chronic MI. Keywords: carvedilol, autonomic nervous system, blood pressure variability, chronic treatment, myocardial infarction Financial support: Acknowledgements to CNPq for providing a scholarship and financial support to E. M. Dantas (141240/2008-3).
doi:10.1016/j.autneu.2011.05.143
P.129 Sympathetic activation after myocardial infarction in the rat: Role of the arterial baroreflex, cardiac afferent reflexes and sex C.J. Barrett, M.I. Pinkham (The University of Auckland — Department of Physiology, New Zealand) The initial sympathetic activation in response to myocardial infarction (MI) is compensatory in nature and is mediated by the arterial baroreflexes and cardiac sensory afferents. However, the increase in sympathetic nerve activity (SNA) after MI is adversely related to patient outcome. Given the sex differences observed in mortality post-MI, we hypothesis that sex differences in the arterial baroreflex and cardiac afferent reflex regulation of SNA could contribute to sex differences in the sympathetic response to MI. Mean arterial pressure, heart rate, and renal SNA were recorded in anesthetized, open chest Wistar rats in response to ligation of the left coronary artery. In males, renal SNA increased immediately following coronary occlusion, and remained significantly elevated for the remaining 2 h (at 120 min post-MI male renal SNA was 18 ± 7% increased vs. −1 ± 3% in shams, p < 0.05). Females with ovaries intact displayed no change to renal SNA in response to MI (1 ± 4% at 120 min post-MI). In females with ovaries removed (OVX) the responses were similar to the males (21 ± 7% at 120 min post-MI). Compared to males, both intact and OVX females had a reduced ability to increase SNA in response to a decrease in arterial pressure. Cardiac afferent reflex responses were recorded in response to application of capsaicin (1–10 μg per 10 μl) to the surface of the left ventricle in baroreceptor denervated rats. The increases in renal SNA in response to capsaicin were significantly greater in males and OVX females than intact females. These results suggest actions of the female sex hormones on the cardiac afferent reflex may be important in mediating the initial renal sympathetic nerve response to MI. The reduced sympathetic activation via the cardiac afferent reflex seen in the intact females could explain why pre-menopausal females are at less risk of sudden cardiac death. Keywords: renal sympathetic nerve activity, myocardial ischemia, sex differences Financial support: Lotteries Health. doi:10.1016/j.autneu.2011.05.144
Neuro-Immunomodulation & Control of Body Temperature P.130 Tumor necrosis factor stimulation of vagal afferent terminal calcium is blocked by cannabinoids R.C. Rogers (Pennington Biomedical Research Center — Laboratory of Autonomic Neuroscience, United States), G.E. Hermann (Pennington Biomedical Research Center — Autonomic Neuroscience, United States) The proinflammatory cytokine tumor necrosis factor (TNF) is released by the activated immune system in infection, cancer, autoimmune disorders, and radiation sickness. TNF can cause the gastric stasis, nausea, emesis, and anorexia common to these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders. Previous work in our laboratory has shown that TNF excitation of vagal afferents occurs as a result of sensitization of ryanodine channels, This, in turn , causes greater stimulus-induced terminal calcium levels and an increased glutamatergic excitatory drive on vago-vagal reflex neurons in the nucleus of the solitary tract [NST) (Rogers et al., 2006; Hermann, Rogers, 2008), Cannabinoids have, for millennia, been used to combat the visceral malaise of chronic diseases associated with TNF release. It is clear that CB1 antiemetic and antinauseagenic effects are directed at structures in the dorsal vagal complex (Derbenev et al., 2004, Van Sickle et al., 2003). Further, CB1 agonists have been shown in cultured neuron preparations to depress presynaptic activity by inhibiting ryanodine channel mediated calcium release (Zhaung, 2005). We applied laser confocal calcium imaging methods in in vitro slice preparations of the NST to directly examine whether CB1 cannabinoid agonists can interfere with the presynaptic effects of TNF to amplify visceral afferent signaling. We replicated our earlier work (2006) showing that calcium signals generated in vagal afferent terminals in response to stimulation is significantly enhanced by pretreatment with TNF. Predictably, the cannabinoid CB1 agonist WIN-2 depressed calcium signaling in vagal afferents in response to stimulation and completely blocked the TNF afferent amplification effect. Thus, CB1 agonists can block the effects of TNF to activate vagal afferents. This interaction may provide the basis for CB1 agonist effects to suppress the nausea of chronic disease. Keywords: cachexia, vagus, calcium imaging, cytokines, solitary nucleus Financial support: NIH Grants NS 52142, NS 60664.
doi:10.1016/j.autneu.2011.05.145
P.131 Changes in expression and distribution patterns of Mas-related gene receptors in the murine ileum caused by intestinal inflammation L.R. Avula (Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, Belgium), L. Van Nassauw (Laboratory of Cell Biology and Histology and Laboratory of Human Anatomy & Embryology, Department of Veterinary Sciences and Department of Antwerp Surgical Training, Anatomy and Research Center, Belgium), E. Stuyven (Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Belgium), R. Buckinx, K. Alpaerts, D. Adriaensen (Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, Belgium), H. Favoreel, E. Cox, J.P. Timmermans (Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Belgium)
Abstracts / Autonomic Neuroscience: Basic and Clinical 163 (2011) 1–133
HCarvD treatment reduced significantly this component (11.13 ± 9.32 mm Hg2 SP, 13.30 ± 8.39 mm Hg2 SLD, 9.67 ± 6.63 mm Hg2 SHD vs. 2.92 ± 3.75 mm Hg2 MIHD; P < 0.05). Neither MI nor Carv treatment altered HF (3.55± 2.47 mm Hg2 SP). MI attenuated (3.74 ± 2.96 SP vs. 0.92 ± 0.76 MIP; P > 0.05) and HCarvD reduced the LF/HF ratio (3.74 ± 2.96 SP, 3.30± 2.84 SLD, 3.37 ± 2.51 SHD vs. 0.49 ± 0.48 MIHD; P < 0.05). Conclusion: LCarvD restores the depressed BPV in rats with chronic MI. Keywords: carvedilol, autonomic nervous system, blood pressure variability, chronic treatment, myocardial infarction Financial support: Acknowledgements to CNPq for providing a scholarship and financial support to E. M. Dantas (141240/2008-3).
doi:10.1016/j.autneu.2011.05.143
P.129 Sympathetic activation after myocardial infarction in the rat: Role of the arterial baroreflex, cardiac afferent reflexes and sex C.J. Barrett, M.I. Pinkham (The University of Auckland — Department of Physiology, New Zealand) The initial sympathetic activation in response to myocardial infarction (MI) is compensatory in nature and is mediated by the arterial baroreflexes and cardiac sensory afferents. However, the increase in sympathetic nerve activity (SNA) after MI is adversely related to patient outcome. Given the sex differences observed in mortality post-MI, we hypothesis that sex differences in the arterial baroreflex and cardiac afferent reflex regulation of SNA could contribute to sex differences in the sympathetic response to MI. Mean arterial pressure, heart rate, and renal SNA were recorded in anesthetized, open chest Wistar rats in response to ligation of the left coronary artery. In males, renal SNA increased immediately following coronary occlusion, and remained significantly elevated for the remaining 2 h (at 120 min post-MI male renal SNA was 18 ± 7% increased vs. −1 ± 3% in shams, p < 0.05). Females with ovaries intact displayed no change to renal SNA in response to MI (1 ± 4% at 120 min post-MI). In females with ovaries removed (OVX) the responses were similar to the males (21 ± 7% at 120 min post-MI). Compared to males, both intact and OVX females had a reduced ability to increase SNA in response to a decrease in arterial pressure. Cardiac afferent reflex responses were recorded in response to application of capsaicin (1–10 μg per 10 μl) to the surface of the left ventricle in baroreceptor denervated rats. The increases in renal SNA in response to capsaicin were significantly greater in males and OVX females than intact females. These results suggest actions of the female sex hormones on the cardiac afferent reflex may be important in mediating the initial renal sympathetic nerve response to MI. The reduced sympathetic activation via the cardiac afferent reflex seen in the intact females could explain why pre-menopausal females are at less risk of sudden cardiac death. Keywords: renal sympathetic nerve activity, myocardial ischemia, sex differences Financial support: Lotteries Health. doi:10.1016/j.autneu.2011.05.144
Neuro-Immunomodulation & Control of Body Temperature P.130 Tumor necrosis factor stimulation of vagal afferent terminal calcium is blocked by cannabinoids R.C. Rogers (Pennington Biomedical Research Center — Laboratory of Autonomic Neuroscience, United States), G.E. Hermann (Pennington Biomedical Research Center — Autonomic Neuroscience, United States) The proinflammatory cytokine tumor necrosis factor (TNF) is released by the activated immune system in infection, cancer, autoimmune disorders, and radiation sickness. TNF can cause the gastric stasis, nausea, emesis, and anorexia common to these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders. Previous work in our laboratory has shown that TNF excitation of vagal afferents occurs as a result of sensitization of ryanodine channels, This, in turn , causes greater stimulus-induced terminal calcium levels and an increased glutamatergic excitatory drive on vago-vagal reflex neurons in the nucleus of the solitary tract [NST) (Rogers et al., 2006; Hermann, Rogers, 2008), Cannabinoids have, for millennia, been used to combat the visceral malaise of chronic diseases associated with TNF release. It is clear that CB1 antiemetic and antinauseagenic effects are directed at structures in the dorsal vagal complex (Derbenev et al., 2004, Van Sickle et al., 2003). Further, CB1 agonists have been shown in cultured neuron preparations to depress presynaptic activity by inhibiting ryanodine channel mediated calcium release (Zhaung, 2005). We applied laser confocal calcium imaging methods in in vitro slice preparations of the NST to directly examine whether CB1 cannabinoid agonists can interfere with the presynaptic effects of TNF to amplify visceral afferent signaling. We replicated our earlier work (2006) showing that calcium signals generated in vagal afferent terminals in response to stimulation is significantly enhanced by pretreatment with TNF. Predictably, the cannabinoid CB1 agonist WIN-2 depressed calcium signaling in vagal afferents in response to stimulation and completely blocked the TNF afferent amplification effect. Thus, CB1 agonists can block the effects of TNF to activate vagal afferents. This interaction may provide the basis for CB1 agonist effects to suppress the nausea of chronic disease. Keywords: cachexia, vagus, calcium imaging, cytokines, solitary nucleus Financial support: NIH Grants NS 52142, NS 60664.
doi:10.1016/j.autneu.2011.05.145
P.131 Changes in expression and distribution patterns of Mas-related gene receptors in the murine ileum caused by intestinal inflammation L.R. Avula (Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, Belgium), L. Van Nassauw (Laboratory of Cell Biology and Histology and Laboratory of Human Anatomy & Embryology, Department of Veterinary Sciences and Department of Antwerp Surgical Training, Anatomy and Research Center, Belgium), E. Stuyven (Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Belgium), R. Buckinx, K. Alpaerts, D. Adriaensen (Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, Belgium), H. Favoreel, E. Cox, J.P. Timmermans (Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Belgium)