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Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata

血管紧张素II 诱导产生的活性氧簇参与延髓的心血管反射

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Abstract

The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the cardiovascular reflexes within the brainstem. It is well-known that one of the mechanisms by which angiotensin II exerts its effect is via the activation of pathways that generate reactive oxygen species (ROS). In the central nervous system, ROS are reported to be involved in several pathological diseases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.

摘要

脑干是中枢神经系统中的一个重要部位, 参与心血管反射, 例如压力感受性反射和外周化学感受性反射。 孤束核和延髓头端腹外侧是脑干中重要的两个部位, 在心血管自主调节中扮演重要角色。神经递质血管紧张素II 能通过活化一些通路, 诱导产生活性氧簇, 进而参与脑干心血管反射。研究表明, 在中枢神经系统中, 活性氧簇 与一些病理疾病相关, 例如高血压、心衰竭和睡眠性呼吸暂停。然而, 活性氧簇在脑干心血管反射中的作用目前 尚不明确。本文主要就最近关于活性氧簇在脑干中压力感受性反射和外周化学感受性反射中作用的一些发现进行 综述及讨论。

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References

  1. Guyenet PG. The sympathetic control of blood pressure. Nat Rev Neurosci 2006, 7(5): 335–346.

    Article  PubMed  CAS  Google Scholar 

  2. Braga VA, Paton JF, Machado BH. Ischaemia-induced sympathoexcitation in spinalyzed rats. Neurosci Lett 2007, 415(1): 73–76.

    Article  PubMed  CAS  Google Scholar 

  3. Braga VA, Soriano RN, Braccialli AL, de Paula PM, Bonagamba LG, Paton JF, et al. Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation. J Physiol 2007, 581(3): 1129–1145.

    Article  PubMed  CAS  Google Scholar 

  4. Potts JT, Paton JF, Mitchell JH, Garry MG, Kline G, Anguelov PT, et al. Contraction-sensitive skeletal muscle afferents inhibit arterial baroreceptor signalling in the nucleus of the solitary tract: role of intrinsic GABA interneurons. Neuroscience 2003, 119: 201–214.

    Article  PubMed  CAS  Google Scholar 

  5. Franchini KG, Krieger EM. Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN. J Auton Nerv Syst 1993, 42: 63–70.

    Article  PubMed  CAS  Google Scholar 

  6. Braga VA, Soriano RN, Machado BH. Sympathoexcitatory response to peripheral chemoreflex activation is enhanced in juvenile rats exposed to chronic intermittent hypoxia. Exp Physiol 2006, 91(6): 1025–1031.

    Article  PubMed  Google Scholar 

  7. Braga VA, Burmeister MA, Sharma RV, Davisson RL. Cardiovascular responses to peripheral chemoreflex activation and comparison of different methods to evaluate baroreflex gain in conscious mice using telemetry. Am J Physiol Regul Integr Comp Physiol 2008, 295(4): R1168–R1174.

    Article  PubMed  CAS  Google Scholar 

  8. Antunes VR, Braga VA, Machado BH. Autonomic and respiratory responses to microinjection of ATP into the intermediate or caudal nucleus tractus solitarius in the working heart-brainstem preparation of the rat. Clin Exp Pharmacol Physiol 2005, 32(5–6): 467–472.

    Article  PubMed  CAS  Google Scholar 

  9. Braga VA, Machado BH. Chemoreflex sympathoexcitation was not altered by the antagonism of glutamate receptors in the commissural nucleus tractus solitarii in the working heart-brainstem preparation of rats. Exp Physiol 2006, 91(3): 551–559.

    Article  PubMed  CAS  Google Scholar 

  10. Machado BH. Neurotransmission of the cardiovascular reflexes in the nucleus tractus solitarii of awake rats. Ann N Y Acad Sci 2001, 940: 179–196.

    Article  PubMed  CAS  Google Scholar 

  11. Braga VA, Antunes VR, Machado BH. Autonomic and respiratory responses to microinjection of L-glutamate into the commissural subnucleus of the NTS in the working heart-brainstem preparation of the rat. Brain Res 2006, 1093(1): 150–160.

    Article  PubMed  CAS  Google Scholar 

  12. Zubcevic J, Potts JT. Role of GABAergic neurones in the nucleus tractus solitarii in modulation of cardiovascular activity. Exp Physiol 2010, 95(9): 909–918.

    PubMed  CAS  Google Scholar 

  13. Lin LH, Taktakishvili OM, Talman WT. Colocalization of neurokinin-1, N-methyl-D-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii. Neuroscience 2008, 154(2): 690–700.

    Article  PubMed  CAS  Google Scholar 

  14. Wang WZ, Gao L, Pan YX, Zucker IH, Wang W. AT1 receptors in the nucleus tractus solitarii mediate the interaction between the baroreflex and the cardiac sympathetic afferent reflex in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 2007, 292(3): R1137–R1145.

    Article  PubMed  CAS  Google Scholar 

  15. Waki H, Kasparov S, Wong LF, Murphy D, Shimizu T, Paton JF. Chronic inhibition of endothelial nitric oxide synthase activity in nucleus tractus solitarii enhances baroreceptor reflex in conscious rats. J Physiol 2003, 546(1): 233–242.

    Article  PubMed  CAS  Google Scholar 

  16. Scislo TJ, Ergene E, O’Leary DS. Impaired arterial baroreflex regulation of heart rate after blockade of P2-purinoceptors in the nucleus tractus solitarius. Brain Res Bull 1998, 47(1): 63–67.

    Article  PubMed  CAS  Google Scholar 

  17. Mayorov DN, Head GA. Glutamate receptors in RVLM modulate sympathetic baroreflex in conscious rabbits. Am J Physiol Regul Integr Comp Physiol 2003, 284(2): R511–R519.

    PubMed  CAS  Google Scholar 

  18. Alzamora AC, Santos RA, Campagnole-Santos MJ. Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla. Am J Physiol Regul Integr Comp Physiol 2006, 290(4): R1027–R1034.

    Article  PubMed  CAS  Google Scholar 

  19. Wang Y, Patel KP, Cornish KG, Channon KM, Zucker IH. nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. Am J Physiol Heart Circ Physiol 2003, 285(4): H1660–H1667.

    PubMed  CAS  Google Scholar 

  20. Paton JF, Deuchars J, Ahmad Z, Wong LF, Murphy D, Kasparov S. Adenoviral vector demonstrates that angiotensin II-induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat. J Physiol 2001, 531(2): 445–458.

    Article  PubMed  CAS  Google Scholar 

  21. Moraes DJ, Bonagamba LG, Zoccal DB, Machado BH. Modulation of respiratory responses to chemoreflex activation by L-glutamate and ATP in the rostral ventrolateral medulla of awake rats. Am J Physiol Regul Integr Comp Physiol 2011 (in press).

  22. Nunes FC, Ribeiro TP, França-Silva MS, Medeiros IA, Braga VA. Superoxide scavenging in the rostral ventrolateral medulla blunts the pressor response to peripheral chemoreflex activation. Brain Res 2010, 1351: 141–149.

    Article  PubMed  CAS  Google Scholar 

  23. Makeham JM, Goodchild AK, Pilowsky PM. NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex. Am J Physiol Regul Integr Comp Physiol 2005, 288(6): R1707–R1715.

    Article  PubMed  CAS  Google Scholar 

  24. Harrison DG, Dikalov S. Oxidative events in cell and vascular biology. In: Re RN, DiPette DJ, Schriffrin EL, Sowers JR (eds). Molecular mechanisms in hypertension. 1st ed. Abingdon (UK): Taylor & Francis Medical Books, 2006: 297–320.

    Google Scholar 

  25. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994, 74: 1141–1148.

    PubMed  CAS  Google Scholar 

  26. Zimmerman MC, Lazartigues E, Lang JA, Sinnayah P, Ahmad IM, Spitz DR, et al. Superoxide mediates the actions of angiotensin II in the central nervous system. Circ Res 2002, 91(11): 1038–1045.

    Article  PubMed  CAS  Google Scholar 

  27. Zimmerman MC, Davisson RL. Redox signaling in central neural regulation of cardiovascular function. Prog Biophys Mol Biol 2004, 84(2–3): 125–149.

    Article  PubMed  CAS  Google Scholar 

  28. Braga VA. Dietary salt enhances angiotensin-II-induced superoxide formation in the rostral ventrolateral medulla. Auton Neurosci 2010, 155(1–2): 14–18.

    Article  PubMed  CAS  Google Scholar 

  29. Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL. Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res 2004, 95(2): 210–216.

    Article  PubMed  CAS  Google Scholar 

  30. Peterson JR, Burmeister MA, Tian X, Zhou Y, Guruju MR, Stupinski JA, et al. Genetic silencing of Nox2 and Nox4 reveals differential roles of these NADPH oxidase homologues in the vasopressor and dipsogenic effects of brain angiotensin II. Hypertension 2009, 54(5): 1106–1114.

    Article  PubMed  CAS  Google Scholar 

  31. Allen AM, Chai SY, Sexton PM, Lewis SJ, Verberne AJ, Jarrott B, et al. Angiotensin II receptors and angiotensin converting enzyme in the medulla oblongata. Hypertension 1987, 9: 198–205.

    Google Scholar 

  32. Nunes FC, Braga VA. Chronic angiotensin II infusion modulates angiotensin II type I receptor expression in the subfornical organ and the rostral ventrolateral medulla in hypertensive rats. J Renin Angiotensin Aldosterone Syst 2011. Doi: 10.1177/1470320310394891.

  33. Braga VA. Differential brain angiotensin-II type I receptor expression in hypertensive rats. J Vet Sci 2011 (in press).

  34. Li YW, Guyenet PG. Angiotensin II decreases a resting K+ conductance in rat bulbospinal neurons of the C1 area. Circ Res 1996, 78: 274–282.

    PubMed  CAS  Google Scholar 

  35. Andreatta SH, Averill DB, Santos RA, Ferrario CM. The ventrollateral medulla. A new site of action of the renin-angiotensin system. Hypertension 1988, 11: 163–166.

    Google Scholar 

  36. Hirooka Y, Potts PD, Dampney RA. Role of angiotensin II receptor subtypes in mediating the sympathoexcitatory effects of exogenous and endogenous angiotensin peptides in the rostral ventrolateral medulla of the rabbit. Brain Res 1997, 772: 107–114.

    Article  PubMed  CAS  Google Scholar 

  37. Gao L, Wang W, Li YL, Schultz HD, Liu D, Cornish KG, et al. Sympathoexcitation by central ANG II: roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM. Am J Physiol Heart Circ Physiol 2005, 288(5): H2271–H2279.

    Article  PubMed  CAS  Google Scholar 

  38. Kishi T, Hirooka Y, Konno S, Ogawa K, Sunagawa K. Angiotensin II type 1 receptor-activated caspase-3 through ras/mitogen-activated protein kinase/extracellular signal-regulated kinase in the rostral ventrolateral medulla is involved in sympathoexcitation in strokeprone spontaneously hypertensive rats. Hypertension 2010, 55(2): 291–297.

    Article  PubMed  CAS  Google Scholar 

  39. Botelho-Ono MS, Pina HV, Sousa KH, Nunes FC, Medeiros IA, Braga VA. Acute superoxide scavenging restores depressed baroreflex sensitivity in renovascular hypertensive rats. Auton Neurosci 2011, 159(1–2): 38–44.

    Article  PubMed  CAS  Google Scholar 

  40. Giusti MF, Sato MA, Cardoso LM, Braga VA, Colombari E. Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats. Neurosci Lett 2011, 489(2): 115–118.

    Article  PubMed  CAS  Google Scholar 

  41. Nishi EE, Oliveira-Sales EB, Bergamaschi CT, Oliveira TG, Boim MA, Campos RR. Chronic antioxidant treatment improves arterial renovascular hypertension and oxidative stress markers in the kidney in Wistar rats. Am J Hypertens 2010, 23(5): 473–480.

    Article  PubMed  CAS  Google Scholar 

  42. Guimaraes DD, Oliveira-Monteiro NM, Braga VA. Acute superoxide scavenging restores depressed baroreflex sensitivity in spontaneously hypertensive rats. Auton Neurosci 2011 (in press).

  43. Harrison DG, Gongora MC. Oxidative stress and hypertension. Med Clin North Am 2009, 93(3): 621–635.

    Article  PubMed  CAS  Google Scholar 

  44. Braga VA, Medeiros IA, Ribeiro TP, Franca-Silva MS, Botelho-Ono MS, Guimaraes DD. Angiotensin-II-derived reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension. Braz J Med Biol Res 2011 (in press).

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, PB, Brazil

    Valdir A. Braga & Mariana G. Jovita

  2. Department of Physiology and Pathology, São Paulo State University, UNESP, Araraquara, SP, Brazil

    Eduardo Colombari

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  1. Valdir A. Braga
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Correspondence to Valdir A. Braga.

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Braga, V.A., Colombari, E. & Jovita, M.G. Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata. Neurosci. Bull. 27, 269–274 (2011). https://doi.org/10.1007/s12264-011-1529-z

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