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.

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 Preserved glycemic control and baroreflex efficacy in young adult hypertensive female obese Zucker rats

2021 ◽  
Author(s):  
Parul Chaudhary ◽  
Paromita Das-Earl ◽  
Ann M. Schreihofer
Keyword(s):  
Blood Glucose ◽  
Glycemic Control ◽  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Zucker Rats ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Obese Zucker Rats ◽  
Fos Expression ◽  
Old Females

Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 months of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-month-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-month-old OZRs. We hypothesized that 3-month-old female OZRs maintain NTS activation and baroreflexes coincident with glycemic control. We also hypothesized that 6-month-old female OZRs develop impaired baroreflexes with hyperglycemia and diminished NTS activation. In 12-16-week-old females, sympathetic nerve activity (SNA) and arterial pressure (AP) were higher in OZRs than LZRs. However, baroreflex-mediated inhibition of SNA and bradycardia were equivalent in female OZRs and LZRs. Unlike deficits in male OZRs, female OZRs and LZRs had no differences in phenylephrine-induced c-Fos expression in NTS or decreases in SNA and AP evoked by glutamate into NTS. Compared to hyperglycemia in male OZRs (217.9±34.4mg/dl), female OZRs had normal fed blood glucose levels (108.2±1.6mg/dl in LZRs and 113.6±3.5mg/dl in OZRs) with emerging glucose intolerance. Conscious 24-27-week-old female OZRs had impaired baroreflex-mediated bradycardia, but fed blood glucose was modestly elevated (124.2±5.2mg/dl) and phenylephrine-induced c-Fos expression in NTS was comparable to LZRs. These data suggest better glycemic control in 3-month-old female OZRs prevents diminished NTS activation and baroreflexes, supporting the notion that hyperglycemia impairs these responses in male OZRs. However, 6-month-old female OZRs had impaired baroreflex efficacy without diminished NTS activation or pronounced hyperglycemia, suggesting baroreflex deficits develop by different mechanisms in female and male OZRs.

scholarly journals Rostral ventrolateral medullary but not medullary lateral tegmental field neurons mediate sympatho-sympathetic reflexes in cats

2010 ◽  
Vol 299 (5) ◽  
pp. R1269-R1278 ◽  
Author(s):  
Susan M. Barman ◽  
Hakan S. Orer
Keyword(s):  
Nmda Receptors ◽  
Nucleus Tractus Solitarius ◽  
Excitatory Amino Acid ◽  
Critical Role ◽  
Area Under The Curve ◽  
Splanchnic Nerve ◽  
Ventrolateral Medulla ◽  
Afferent Fibers ◽  
The Right ◽  
Stimulation Of

This study was designed to build on past work from this laboratory by testing the hypothesis that medullary lateral tegmental field (LTF) neurons play a critical role in mediating sympathoexcitatory responses to activation of sympathetic afferent fibers. We studied the effects of microinjection of N-methyl-d-aspartate (NMDA) or non-NMDA receptor antagonists or muscimol bilaterally into the LTF on the area under the curve of the computer-averaged sympathoexcitatory potential in the right inferior cardiac nerve elicited by short trains of stimuli applied to afferent fibers in the left inferior cardiac or left splanchnic nerve (CN, SN) of baroreceptor-denervated and vagotomized cats anesthetized with a mixture of diallylbarbiturate and urethane. In contrast to our hypothesis, sympathoexcitatory responses to stimulation of CN ( n = 5–7) or SN ( n = 4–7) afferent fibers were not significantly affected by these procedures. We then determined whether the rostral and caudal ventrolateral medulla (RVLM, CVLM) and nucleus tractus solitarius (NTS) were involved in mediating these reflexes. Blockade of non-NMDA, but not NMDA, receptors in the RVLM significantly reduced the area under the curve of the sympathoexcitatory responses to electrical stimulation of either CN ( P = 0.0110; n = 6) or SN ( P = 0.0131; n = 5) afferent fibers. Neither blockade of excitatory amino acid receptors nor chemical inactivation of CVLM or NTS significantly affected the responses. These data show that activation of non-NMDA receptors in the RVLM is a critical step in mediating the sympatho-sympathetic reflex.

Brain stem control of arterial pressure in chronic arterial baroreceptor-denervated rats

2005 ◽  
Vol 289 (6) ◽  
pp. R1746-R1755 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Satoru Ito ◽  
Alan F. Sved
Keyword(s):  
Arterial Pressure ◽  
Vascular Reactivity ◽  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Excitatory Input ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Afferent Nerves ◽  
Pressor Responses

Interruption of the baroreceptor reflex by transection of afferent nerves (sinoaortic denervation; SAD) or lesions of nucleus tractus solitarius (NTS) elevates sympathetic nerve activity (SNA) and arterial pressure (AP). However, within 1 wk, mean AP returns to normal despite the absence of baroreflexes. In this study, we examine central mechanisms that control AP in chronic baroreceptor-denervated rats. In urethane-anesthetized rats (1.5g/kg iv) after autonomic ganglionic blockade (5 mg/kg iv chlorisondamine), α1-adrenergic-mediated pressor responses (1–100 μg/kg iv phenylephrine) were not altered by chronic lesions of NTS, indicating vascular reactivity to sympathetic stimulation is normal. Transection of the spinal cord at T1 profoundly decreased AP and was not further reduced by chlorisondamine in control or denervated rats. Inhibition of the rostral ventrolateral medulla (RVLM) by microinjections of muscimol (100 pmol/side) decreased AP to levels not further reduced by chlorisondamine in control rats, rats with SAD, and rats with NTS lesions. Blockade of GABAA receptors in the RVLM (50 pmol/side bicuculline) increased AP similarly in control rats and denervated rats. In agreement, inhibition of the caudal ventrolateral medulla (CVLM) by microinjections of muscimol or blockade of glutamatergic inputs (2.7 nmol/side kynurenate) produced comparable increases in AP in control and denervated rats. These data suggest the RVLM continues to drive the SNA that regulates AP in the chronic absence of baroreceptor inputs. In addition, despite the absence of a tonic excitatory input from NTS, in chronic baroreceptor-denervated rats glutamatergic inputs drive the CVLM to tonically inhibit the RVLM. Baroreceptor-independent regulation of the ventrolateral medulla may underlie central mechanisms contributing to the long-term control of AP.

Stimulation of feeding in lean but not in obese Zucker rats by a selective neuropeptide Y Y5 receptor agonist

Neuroreport ◽  
1998 ◽  
Vol 9 (11) ◽  
pp. 2675-2677 ◽  
Author(s):  
Philipp Wyss ◽  
Nigel Levens ◽  
Alain Stricker-Krongrad
Keyword(s):  
Neuropeptide Y ◽  
Receptor Agonist ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Stimulation Of
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