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CENTRAL MECHANISMS INVOLVED IN THE CONTROL OF ARTERIAL PRESSURE AND FLUID-ELECTROLYTE BALANCE:

CENTRAL MECHANISMS INVOLVED IN THE CONTROL OF ARTERIAL PRESSURE AND FLUID-ELECTROLYTE BALANCE: IMPORTANCE OF THE AV3V REGION José V. Menani Department of Physiology and Pathology, School of Dentistry, São Paulo State University, UNESP, Araraquara, SP, Brazil.

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CENTRAL MECHANISMS INVOLVED IN THE CONTROL OF ARTERIAL PRESSURE AND FLUID-ELECTROLYTE BALANCE:

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  1. CENTRAL MECHANISMS INVOLVED IN THE CONTROL OF ARTERIAL PRESSURE AND FLUID-ELECTROLYTE BALANCE: IMPORTANCE OF THE AV3V REGION José V. Menani Department of Physiology and Pathology, School of Dentistry, São Paulo State University, UNESP, Araraquara, SP, Brazil.

  2. CENTRAL MECHANISMS INVOLVED IN THE CONTROL OF ARTERIAL PRESSURE AND FLUID-ELECTROLYTE BALANCE: IMPORTANCE OF THE AV3V REGION José V. Menani Department of Physiology and Pathology, School of Dentistry, São Paulo State University, UNESP, Araraquara, SP, Brazil.

  3. IMPORTANT FOREBRAIN AND HINDBRAIN AREAS INVOLVED IN CARDIOVASCULAR REGULATION MSA CHEMORECEPTOR BARORECEPTOR NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  4. AV3V REGION (anteroventral 3rd ventricle region) AV3V REGION AV3V REGION MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis (Brody and Johnson, 1978)

  5. AV3V REGION (Brody and Johnson, 1978)

  6. SHAM LESION ELECTROLYTICAV3V LESION (ARROW) ac 500 mm 500 mm oc

  7. AV3V LESIONS ABOLISH THE PRESSOR RESPONSE TO ANG II (12 ng) INTRACEREBROVENTRICULARLY

  8. AV3V LESIONS ABOLISH THE PRESSOR RESPONSE TO INTRAPERITONEAL PILOCARPINE (1 mg/kg) Effects of AV3V lesion on the pressor response to ip pilocarpine Sham (1 hour) Sham (2 days) AV3V lesion (1 hour) AV3V lesion (2 days) *different from sham +different from pre-pilocarpine PILOCARPINE : cholinergic agonist 1 h and 2 days after lesion N = 8

  9. AV3V LESIONS REDUCE THE PRESSOR RESPONSE TO INJECTION OF CARBACHOL (2 nmol) IN THE FOREBRAIN LV = lateral ventricle SFO = subfornical organ MSA = medial septal area VMH = ventromedial hypothalamus CARBACHOL: muscarinic agonist

  10. AV3V LESIONS REDUCE THE DIPSOGENIC RESPONSE TO INJECTION OF CARBACHOL (2 nmol) IN THE FOREBRAIN LV = lateral ventricle SFO = subfornical organ MSA = medial septal area VMH = ventromedial hypothalamus CARBACHOL: muscarinic agonist

  11. AV3V LESIONS REDUCE THE NATRIURETIC RESPONSE TO INJECTION OF CARBACHOL (2 nmol) IN THE FOREBRAIN LV = lateral ventricle SFO = subfornical organ MSA = medial septal area VMH = ventromedial hypothalamus CARBACHOL: muscarinic agonist

  12. PRESSOR, DIPSOGENIC AND NATRIURETIC RESPONSES TO CHOLINERGIC ACTIVATION OF FOREBRAIN AREAS LIKE MSA, SFO OR VMH DEPEND ON THE AV3V REGION MSA CHEMORECEPTOR BARORECEPTOR AV3V REGION NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  13. AV3V REGION IS THE AV3V REGION ALSO IMPORTANT FOR THE PRESSOR RESPONSES PRODUCED BY THE ACTIVATION OF HINDBRAIN AREAS LIKE THE NTS OR RVLM? MSA CHEMORECEPTOR BARORECEPTOR NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  14. NTS injection glutamate substance P AV3V lesion

  15. AV3V LESIONS ABOLISH THE PRESSOR RESPONSE TO INJECTION OF GLUTAMATE INTO THE NTS

  16. AV3V LESIONS (1 DAY) PRODUCE NO EFFECT IN THE PRESSOR RESPONSE TO INJECTION OF SUBSTANCE P INTO THE NTS

  17. AV3V LESION RVLM injection glutamate

  18. AV3V LESIONS (1 DAY) REDUCE THE PRESSOR RESPONSE TO INJECTION OF GLUTAMATE INTO THE RVLM

  19. AV3V LESIONS (15 DAYS) REDUCE THE PRESSOR RESPONSE TO INJECTION OF GLUTAMATE INTO THE RVLM

  20. AV3V REGION PRESSOR RESPONSES TO GLUTAMATERGIC ACTIVATION OF HINDBRAIN AREAS LIKE NTS AND RVLM ALSO DEPEND ON FACILITATORY SIGNALS FROM AV3V REGION MSA CHEMORECEPTOR BARORECEPTOR NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  21. AV3V LESIONS ALSO REDUCE HYPERTENSION OF 1-KIDNEY, 1-CLIP HYPERTENSIVE RATS

  22. IN SPITE OF THE ANTI-HYPERTENSIVE EFFECTS OF AV3V LESIONS IN DIFFERENT MODELS OF EXPERIMENTAL HYPERTENSION, THESE LESIONS ALONE PRODUCE NO EFFECT IN SPONTANEOULY HYPERTENSIVE RATS (SHR). MIGHT ANOTHER AREA OF THE BRAIN BE INVOLVED IN HYPERTENSION IN SHR? PERIPHERAL CHEMORECEPTOR ACTIVITY IS HIGH IN SHR AND LESIONS OF THE COMMISSURAL PORTION OF THE NTS (COMMNTS) ABOLISH THE PRESSOR RESPONSE TO CHEMORECEPTOR ACTIVATION. THEN, MIGHT COMMNTS LESIONS AFFECT HYPERTENSION IN SHR?

  23. ELECTROLYTIC LESION OF THE COMMNTS (arrows)

  24. ACUTE LESIONS OF THE COMMNTS ABOLISH HYPERTENSION IN SHR Basal MAP of sham- and commNTS-lesioned SHR in the control day (day 0) and days 1, 2, 3, and 4 after sham or commNTS lesions. Akemi Sato M et al. Hypertension 2001;38:560-564

  25. CHRONIC LESIONS OF THE COMMNTS PRODUCE NO EFFECT ON HYPERTENSION IN SHR Basal MAP and HR in sham or commNTS-lesioned SHR on the control day (pre-lesion) and 1, 10, 20, and 30 days after lesions Sato M A et al. Hypertension 2003;42:713-718

  26. ACUTE OR CHRONIC LESIONS OF THE COMMNTS ABOLISH THE PRESSOR RESPONSE TO CHEMOREFLEX ACTIVATION IN SHR Sato M A et al. Hypertension 2003;42:713-718

  27. LESIONS OF THE COMMNTS ABOLISH CHEMOREFLEX CHRONICALLY AND HYPERTENSION ONLY ACUTELY IN SHR MSA CHEMORECEPTOR BARORECEPTOR x NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  28. WHICH MIGHT BE THE EFFECT OF COMBINED COMMNTS AND AV3V LESIONS IN HYPERTENSION IN SHR? MSA CHEMORECEPTOR BARORECEPTOR x x NTS AV3V REGION N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  29. COMBINED COMMNTS AND AV3V LESIONS PERMANENTLY REDUCE HYPERTENSION IN SHR LESION

  30. COMBINED COMMNTS AND AV3V LESIONS PERMANENTLY REDUCE HYPERTENSION IN SHR MSA CHEMORECEPTOR BARORECEPTOR x x AV3V REGION NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  31. x x WHICH MIGHT BE THE EFFECT OF CHEMORECEPTOR DENERVATION IN HYPERTENSION IN SHR? MSA CHEMORECEPTOR BARORECEPTOR NTS N. AMBIGUUS VMH IML MSA = medial septal area VMH = ventromedial hypothalamus SFO = subfornical organ MnPO = median preoptic nucleus AVPV = anteroventral periventricular nuclei OVLT = organum vasculosum of the lamina terminalis PVN = paraventricular hypothalamic nucleus NTS = nucleus of the solitary tract RVL = rostroventrolateral medulla CVL = caudoventrolateral medulla IML = spinal intermediolateral column RVL CVL PARASYMPATHETIC (Modified from Westerhaus and Loewy, J. Comp. Neurol., 1999)

  32. THE REMOVAL OF CHEMORECEPTOR SIGNALS BY CAROTID SINUS DENERVATION (CSD) REDUCES HYPERTENSION IN SHR SHR CSD WISTAR SHAM SHR SHAM 200 BLOOD PRESSURE (mmHg) 150 100 HEART RATE (bpm) 400 300 Abdala AP, McBryde FD, Marina N, Hendy EB, Engelman Z, Fudim M, Sobotka PA, Gourine A, Paton J . Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol. 590, 4269-4277, 2012. School of Physiology & Pharmacology, Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol BS81TD, UK. Neuroscience, Physiology & Pharmacology, University College London, London WC1E6BT,UK

  33. BRITISH SCIENTIST PROPOSAL: THEY PLAN TO START TESTING THE EFFECTS OF SURGICAL REMOVAL OF CHEMORECEPTOR AFFERENCES ON HYPERTENSION IN HUMANS, PARTICULARLY IN PATIENTS THAT DO NOT RESPOND TO TRADITIONAL TREATMENTS.

  34. Eduardo Colombari Alexandre A. Vieira Débora S.A. Colombari Ana C.T. Takakura Laurival A. De Luca Jr Antonio S. Valladão Thiago S. Moreira Monica A. Sato Departamento de Fisiologia e Patologia, Faculdade de Odontologia de Araraquara, UNESP

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