Does enhanced respiratory-sympathetic coupling contribute to peripheral neural mechanisms of angiotensin II-salt hypertension?

Glenn M Toney, Gustavo R. Pedrino, Gregory D. Fink, John W. Osborn

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Original languageEnglish
Pages (from-to)587-594
Number of pages8
JournalExperimental Physiology
Volume95
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Angiotensin II
Salts
Hypertension
Neurons
Viscera
Splanchnic Nerves
Diet
Hindlimb
Blood Vessels
Spinal Cord
Norepinephrine
Arterial Pressure
Respiration
Kidney

ASJC Scopus subject areas

  • Physiology

Cite this

Does enhanced respiratory-sympathetic coupling contribute to peripheral neural mechanisms of angiotensin II-salt hypertension? / Toney, Glenn M; Pedrino, Gustavo R.; Fink, Gregory D.; Osborn, John W.

In: Experimental Physiology, Vol. 95, No. 5, 05.2010, p. 587-594.

Research output: Contribution to journalArticle

@article{99be560b765e46d284f2188bb58b980b,
title = "Does enhanced respiratory-sympathetic coupling contribute to peripheral neural mechanisms of angiotensin II-salt hypertension?",
abstract = "Hypertension caused by chronic infusion of angiotensin II (Ang II) in experimental animals is likely to be mediated, at least in part, by an elevation of ongoing sympathetic nerve activity (SNA). However, the contribution of SNA relative to non-neural mechanisms in mediating Ang II-induced hypertension is an area of intense debate and remains unresolved. We hypothesize that sympathoexcitatory actions of Ang II are directly related to the level of dietary salt intake. To test this hypothesis, chronically instrumented rats were placed on a 0.1 (low), 0.4 (normal) or 2.0{\%} NaCl diet (high) and, following a control period, administered Ang II (150 ng kg-1 min-1, s.c.) for 10-14 days. The hypertensive response to Ang II was greatest in rats on the high-salt diet (Ang II-salt hypertension), which was associated with increased 'whole body' sympathetic activity as measured by noradrenaline spillover and ganglionic blockade. Indirect and direct measures of organ-specific SNA revealed a distinct 'sympathetic signature' in Ang II-salt rats characterized by increased SNA to the splanchnic vascular bed, transiently reduced renal SNA and no change in SNA to the hindlimbs. Electrophysiological experiments indicate that increased sympathetic outflow in Ang II-salt rats is unlikely to involve activation of rostral ventrolateral medulla (RVLM) vasomotor neurons with barosensitive cardiac rhythmic discharge. Instead, another set of RVLM neurons that discharge in discrete bursts have exaggerated spontaneous activity in rats with Ang II-salt hypertension. Although their discharge is not cardiac rhythmic at resting levels of arterial pressure, it nevertheless appears to be barosensitive. Therefore, these burst-firing RVLM neurons presumably serve a vasomotor function, consistent with their having axonal projections to the spinal cord. Bursting discharge of these neurons is respiratory rhythmic and driven by the respiratory network. Given that splanchnic SNA is strongly coupled to respiration, we hypothesize that enhanced central respiratory-vasomotor neuron coupling in the RVLM could be an important mechanism that contributes to exaggerated splanchnic sympathetic outflow in Ang II-salt hypertension. This hypothesis remains to be tested directly in future investigations.",
author = "Toney, {Glenn M} and Pedrino, {Gustavo R.} and Fink, {Gregory D.} and Osborn, {John W.}",
year = "2010",
month = "5",
doi = "10.1113/expphysiol.2009.047399",
language = "English",
volume = "95",
pages = "587--594",
journal = "Experimental Physiology",
issn = "0958-0670",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Does enhanced respiratory-sympathetic coupling contribute to peripheral neural mechanisms of angiotensin II-salt hypertension?

AU - Toney, Glenn M

AU - Pedrino, Gustavo R.

AU - Fink, Gregory D.

AU - Osborn, John W.

PY - 2010/5

Y1 - 2010/5

N2 - Hypertension caused by chronic infusion of angiotensin II (Ang II) in experimental animals is likely to be mediated, at least in part, by an elevation of ongoing sympathetic nerve activity (SNA). However, the contribution of SNA relative to non-neural mechanisms in mediating Ang II-induced hypertension is an area of intense debate and remains unresolved. We hypothesize that sympathoexcitatory actions of Ang II are directly related to the level of dietary salt intake. To test this hypothesis, chronically instrumented rats were placed on a 0.1 (low), 0.4 (normal) or 2.0% NaCl diet (high) and, following a control period, administered Ang II (150 ng kg-1 min-1, s.c.) for 10-14 days. The hypertensive response to Ang II was greatest in rats on the high-salt diet (Ang II-salt hypertension), which was associated with increased 'whole body' sympathetic activity as measured by noradrenaline spillover and ganglionic blockade. Indirect and direct measures of organ-specific SNA revealed a distinct 'sympathetic signature' in Ang II-salt rats characterized by increased SNA to the splanchnic vascular bed, transiently reduced renal SNA and no change in SNA to the hindlimbs. Electrophysiological experiments indicate that increased sympathetic outflow in Ang II-salt rats is unlikely to involve activation of rostral ventrolateral medulla (RVLM) vasomotor neurons with barosensitive cardiac rhythmic discharge. Instead, another set of RVLM neurons that discharge in discrete bursts have exaggerated spontaneous activity in rats with Ang II-salt hypertension. Although their discharge is not cardiac rhythmic at resting levels of arterial pressure, it nevertheless appears to be barosensitive. Therefore, these burst-firing RVLM neurons presumably serve a vasomotor function, consistent with their having axonal projections to the spinal cord. Bursting discharge of these neurons is respiratory rhythmic and driven by the respiratory network. Given that splanchnic SNA is strongly coupled to respiration, we hypothesize that enhanced central respiratory-vasomotor neuron coupling in the RVLM could be an important mechanism that contributes to exaggerated splanchnic sympathetic outflow in Ang II-salt hypertension. This hypothesis remains to be tested directly in future investigations.

AB - Hypertension caused by chronic infusion of angiotensin II (Ang II) in experimental animals is likely to be mediated, at least in part, by an elevation of ongoing sympathetic nerve activity (SNA). However, the contribution of SNA relative to non-neural mechanisms in mediating Ang II-induced hypertension is an area of intense debate and remains unresolved. We hypothesize that sympathoexcitatory actions of Ang II are directly related to the level of dietary salt intake. To test this hypothesis, chronically instrumented rats were placed on a 0.1 (low), 0.4 (normal) or 2.0% NaCl diet (high) and, following a control period, administered Ang II (150 ng kg-1 min-1, s.c.) for 10-14 days. The hypertensive response to Ang II was greatest in rats on the high-salt diet (Ang II-salt hypertension), which was associated with increased 'whole body' sympathetic activity as measured by noradrenaline spillover and ganglionic blockade. Indirect and direct measures of organ-specific SNA revealed a distinct 'sympathetic signature' in Ang II-salt rats characterized by increased SNA to the splanchnic vascular bed, transiently reduced renal SNA and no change in SNA to the hindlimbs. Electrophysiological experiments indicate that increased sympathetic outflow in Ang II-salt rats is unlikely to involve activation of rostral ventrolateral medulla (RVLM) vasomotor neurons with barosensitive cardiac rhythmic discharge. Instead, another set of RVLM neurons that discharge in discrete bursts have exaggerated spontaneous activity in rats with Ang II-salt hypertension. Although their discharge is not cardiac rhythmic at resting levels of arterial pressure, it nevertheless appears to be barosensitive. Therefore, these burst-firing RVLM neurons presumably serve a vasomotor function, consistent with their having axonal projections to the spinal cord. Bursting discharge of these neurons is respiratory rhythmic and driven by the respiratory network. Given that splanchnic SNA is strongly coupled to respiration, we hypothesize that enhanced central respiratory-vasomotor neuron coupling in the RVLM could be an important mechanism that contributes to exaggerated splanchnic sympathetic outflow in Ang II-salt hypertension. This hypothesis remains to be tested directly in future investigations.

UR - http://www.scopus.com/inward/record.url?scp=77951175501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951175501&partnerID=8YFLogxK

U2 - 10.1113/expphysiol.2009.047399

DO - 10.1113/expphysiol.2009.047399

M3 - Article

C2 - 20228120

AN - SCOPUS:77951175501

VL - 95

SP - 587

EP - 594

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 5

ER -