scholarly journals Hypotension‐induced expression of c‐fos in the rostral ventrolateral medulla of lean and obese Zucker rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Priscila S Guimaraes ◽  
Ann M Schreihofer
Keyword(s):  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Zucker Rats ◽  
Induced Expression ◽  
Obese Zucker Rats

scholarly journals Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

2011 ◽  
Vol 301 (1) ◽  
pp. H230-H240 ◽  
Author(s):  
Domitila A. Huber ◽  
Ann M. Schreihofer
Keyword(s):  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Excitatory Input ◽  
Rostral Ventrolateral Medulla ◽  
Male Rats ◽  
Ventrolateral Medulla ◽  
Zucker Rats ◽  
Caudal Ventrolateral Medulla ◽  
Obese Zucker Rats ◽  
Altered Regulation

Obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) compared with lean Zucker rats (LZR). We examined whether altered tonic glutamatergic, angiotensinergic, or GABAergic inputs to the rostral ventrolateral medulla (RVLM) contribute to elevated SNA and MAP in OZR. Male rats (14–18 wk) were anesthetized with urethane (1.5 g/kg iv), ventilated, and paralyzed to record splanchnic SNA, heart rate (HR), and MAP. Inhibition of the RVLM by microinjections of muscimol eliminated SNA and evoked greater decreases in MAP in OZR vs. LZR ( P < 0.05). Antagonism of angiotensin AT1 receptors in RVLM with losartan yielded modest decreases in SNA and MAP in OZR but not LZR ( P < 0.05). However, antagonism of ionotropic glutamate receptors in RVLM with kynurenate produced comparable decreases in SNA, HR, and MAP in OZR and LZR. Antagonism of GABAA receptors in RVLM with gabazine evoked smaller rises in SNA, HR, and MAP in OZR vs. LZR ( P < 0.05), whereas responses to microinjections of GABA into RVLM were comparable. Inhibition of the caudal ventrolateral medulla, a major source of GABA to the RVLM, evoked attenuated rises in SNA and HR in OZR ( P <0.05). Likewise, inhibition of nucleus tractus solitarius, the major excitatory input to caudal ventrolateral medulla, produced smaller rises in SNA and HR in OZR. These results suggest the elevated SNA and MAP in OZR is derived from the RVLM and that enhanced angiotensinergic activation and reduced GABAergic inhibition of the RVLM may contribute to the elevated SNA and MAP in the OZR.

scholarly journals Exaggerated sympathoexcitatory reflexes develop with changes in the rostral ventrolateral medulla in obese Zucker rats

2016 ◽  
Vol 311 (2) ◽  
pp. R243-R253 ◽  
Author(s):  
Domitila A. Huber ◽  
Ann M. Schreihofer
Keyword(s):  
Sciatic Nerve ◽  
Nerve Stimulation ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Zucker Rats ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Obese Zucker Rats ◽  
Sciatic Nerve Stimulation ◽  
Upper Thoracic

Obesity leads to altered autonomic reflexes that reduce stability of mean arterial pressure (MAP). Sympathoinhibitory reflexes such as baroreflexes are impaired, but reflexes that raise MAP appear to be augmented. In obese Zucker rats (OZR) sciatic nerve stimulation evokes larger increases in MAP by unknown mechanisms. We sought to determine the autonomic underpinnings of this enhanced somatic pressor reflex and whether other sympathoexcitatory reflexes are augmented. We also determined whether their final common pathway, glutamatergic activation of the rostral ventrolateral medulla (RVLM), was enhanced in male OZR compared with lean Zucker rats (LZR). Sciatic nerve stimulation or activation of the nasopharyngeal reflex evoked larger rises in splanchnic sympathetic nerve activity (SNA) (79% and 45% larger in OZR, respectively; P < 0.05) and MAP in urethane-anesthetized, ventilated, paralyzed adult OZR compared with LZR. After elimination of baroreflex feedback by pharmacological prevention of changes in MAP and heart rate, these two sympathoexcitatory reflexes were still exaggerated in OZR (167% and 69% larger, respectively, P < 0.05). In adult OZR microinjections of glutamate, AMPA, or NMDA into the RVLM produced larger rises in SNA (∼61% larger in OZR, P < 0.05 for each drug) and MAP, but stimulation of axonal fibers in the upper thoracic spinal cord yielded equivalent responses in OZR and LZR. In juvenile OZR and LZR, sympathoexcitatory reflexes and physiological responses to RVLM activation were comparable. These data suggest that the ability of glutamate to activate the RVLM becomes enhanced in adult OZR and may contribute to the development of exaggerated sympathoexcitatory responses independent of impaired baroreflexes.

scholarly journals Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

2014 ◽  
Vol 306 (9) ◽  
pp. R681-R692 ◽  
Author(s):  
Priscila S. Guimaraes ◽  
Domitila A. Huber ◽  
Maria J. Campagnole-Santos ◽  
Ann M. Schreihofer
Keyword(s):  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Ventrolateral Medulla ◽  
Zucker Rats ◽  
Adult Rats ◽  
Afferent Nerves ◽  
Afferent Fibers ◽  
Obese Zucker Rats ◽  
Fos Expression ◽  
Stimulation Of

Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with adult lean Zucker rats (LZR) and juvenile OZR (6–7 wk). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared with LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brain stem sites that mediate baroreflexes. In conscious adult rats, a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in the nucleus tractus solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR develop impaired glutamatergic activation of the NTS, which likely contributes to attenuated baroreflexes in adult OZR.

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