scholarly journals Exogenous Angiotensin‐(1–12) Impairs Baroreflex Sensitivity in the Solitary Tract Nucleus in Anesthetized Sprague‐Dawley Rats

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Amy C. Arnold ◽  
Mark C. Chappell ◽  
Carlos M. Ferrario ◽  
Debra I. Diz
Keyword(s):  
Baroreflex Sensitivity ◽  
Solitary Tract Nucleus ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

2014 ◽  
Vol 307 (11) ◽  
pp. H1539-H1546 ◽  
Author(s):  
Amy C. Arnold ◽  
Debra I. Diz
Keyword(s):  
Heart Rate ◽  
Receptor Antagonist ◽  
Baroreflex Sensitivity ◽  
Leptin Receptor ◽  
Solitary Tract Nucleus ◽  
Aged Rats ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Baroreflex Function ◽  
Sprague Dawley Rats

The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging.

Regional effect of naltrexone in the nucleus of the solitary tract in blockade of NPY-induced feeding

2000 ◽  
Vol 278 (2) ◽  
pp. R499-R503 ◽  
Author(s):  
C. M. Kotz ◽  
M. J. Glass ◽  
A. S. Levine ◽  
C. J. Billington
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
Paraventricular Nucleus ◽  
Opioid Receptors ◽  
The Other ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Regional Effect ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid

Naltrexone (NLTX) in the nucleus of the solitary tract (NTS) decreases feeding induced by neuropeptide Y (NPY) in the paraventricular nucleus (PVN). We sought to determine the NTS region most sensitive to NLTX blockade of PVN NPY-induced feeding. Male Sprague-Dawley rats were fitted with two cannulas; one in the PVN and one in a hindbrain region: caudal, medial, or rostral NTS or 1 mm outside the NTS. Animals received NLTX (0, 1, 3, 10, and 30 μg in 0.3 μl) into the hindbrain region just prior to PVN NPY (0.5 μg, 0.3 μl) or artificial cerebrospinal fluid (0.3 μl). Food intake was measured at 2 h following injection. PVN NPY stimulated feeding, and NLTX in the medial NTS significantly decreased NPY-induced feeding at 2 h, whereas administration of NLTX in the other hindbrain regions did not significantly influence PVN NPY induced feeding. These data suggest that opioid receptors in the medial NTS are most responsive to feeding signals originating in the PVN after NPY stimulation.

Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract

2005 ◽  
Vol 288 (1) ◽  
pp. H256-H262 ◽  
Author(s):  
Ana Carolina Rodrigues Dias ◽  
Melissa Vitela ◽  
Eduardo Colombari ◽  
Steven W. Mifflin
Keyword(s):  
Nitric Oxide ◽  
Solitary Tract ◽  
Glutamatergic Transmission ◽  
Sprague Dawley ◽  
Renal Sympathetic Nerve Activity ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Nos Inhibitor ◽  
The Right ◽  
Oxide Synthase

The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain areas. Our previous single-cell studies suggested that NO facilitates glutamatergic transmission in the nucleus of the solitary tract (NTS). In this study, we examined the effect of the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) on glutamatergic and reflex transmission in the NTS. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) from Inactin-anesthetized Sprague-Dawley rats. Bilateral microinjections of l-NAME (10 nmol/100 nl) into the NTS did not cause significant changes in basal MAP, HR, or RSNA. Unilateral microinjection of ( RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 1 pmol/100 nl) into the NTS decreased MAP and RSNA. Fifteen minutes after l-NAME microinjections, AMPA-evoked cardiovascular changes were significantly reduced. N-methyl-d-aspartate (NMDA, 0.5 pmol/100 nl) microinjection into the NTS decreased MAP, HR, and RSNA. NMDA-evoked falls in MAP, HR, and RSNA were significantly reduced 30 min after l-NAME. To examine baroreceptor and cardiopulmonary reflex function, l-NAME was microinjected at multiple sites within the rostro-caudal extent of the NTS. Baroreflex function was tested with phenylephrine (PE, 25 μg iv) before and after l-NAME. Five minutes after l-NAME the decrease in RSNA caused by PE was significantly reduced. To examine cardiopulmonary reflex function, phenylbiguanide (PBG, 8 μg/kg) was injected into the right atrium. PBG-evoked hypotension, bradycardia, and RSNA reduction were significantly attenuated 5 min after l-NAME. Our results indicate that inhibition of NOS within the NTS attenuates baro- and cardiopulmonary reflexes, suggesting that NO plays a physiologically significant neuromodulatory role in cardiovascular regulation.

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

2003 ◽  
Vol 285 (6) ◽  
pp. R1276-R1286 ◽  
Author(s):  
Lin Mei ◽  
Jing Zhang ◽  
Steve Mifflin
Keyword(s):  
Amino Acids ◽  
Gaba Receptor ◽  
Receptor Agonist ◽  
Pressor Response ◽  
Afferent Input ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Afferent Inputs ◽  
Inhibitory Amino Acids

Previous studies have demonstrated that microinjection of baclofen, a GABAB receptor agonist, into the nucleus of the solitary tract (NTS) results in an enhanced pressor response in hypertensive (HT) rats compared with normotensive (NT) rats, suggesting a possible alteration in the responses of neurons in this area to activation of GABAB receptors. The following studies were designed to determine whether HT alters the sensitivity of neurons in the NTS to GABA receptor agonists. Sham-operated NT and unilateral nephrectomized, renal-wrap HT Sprague-Dawley rats were anesthetized, and the responses of NTS neurons receiving aortic nerve (AN) afferent inputs to iontophoretic application of GABA, the GABAA receptor agonist muscimol, and the GABAB agonist baclofen were examined. The AN input was classified as monosynaptic (MSN) if the cell responded to each of two stimuli separated by 5 ms with an action potential. If the cell did not respond, the input was considered polysynaptic (PSN). In MSNs, inhibition of AN-evoked discharge by GABA was not altered in 1 wk of HT but was reduced in 4 wk of HT, whereas in PSNs, sensitivity to GABA was reduced at 1 and 4 wk of HT. In HT rats, inhibition of AN-evoked discharge by baclofen was enhanced in MSNs, but not in PSNs, after 1 and 4 wk of HT, whereas inhibition by muscimol was reduced in MSNs and PSNs at 1 and 4 wk of HT. Changes in sensitivity to muscimol and baclofen within MSNs were the same whether the MSN received a slowly or a rapidly conducted AN afferent input. The results demonstrate that early in HT the sensitivity of NTS neurons to inhibitory amino acids is altered and that these changes are maintained for ≥4 wk. The alterations are dependent on the subtype of GABA receptor being activated and whether the neuron receives a mono- or polysynaptic baroreceptor afferent input.

scholarly journals Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex sensitivity in diabetic rats

2008 ◽  
Vol 295 (5) ◽  
pp. H1974-H1981 ◽  
Author(s):  
Jussara M. do Carmo ◽  
John E. Hall ◽  
Alexandre A. da Silva
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Baroreflex Sensitivity ◽  
Control Period ◽  
Diabetic Rats ◽  
System Control ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Control Diabetes

This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 ± 17 mg/dl) and bradycardia (−79 ± 4 beats/min). Leptin decreased glucose levels (165 ± 16 mg/dl) and raised HR to control values (303 ± 10 to 389 ± 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 ± 7 vs. 316 ± 6, −19 ± 2 vs. −43 ± 6, and 39 ± 3 vs. 68 ± 8 beats/min), and leptin treatment restored these variables to normal (300 ± 7, −68 ± 10, and 71 ± 8 beats/min). Leptin normalized BRS (bradycardia, −2.6 ± 0.3, −1.7 ± 0.2, and −3.0 ± 0.5; and tachycardia, −3.2 ± 0.4, −1.9 ± 0.3, and −3.4 ± 0.3 beats·min−1·mmHg−1 for control, diabetes, and leptin) and HR variability (23 ± 4 to 11 ± 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.

Autonomic control after blockade of the norepinephrine transporter: a model of orthostatic intolerance

2002 ◽  
Vol 93 (6) ◽  
pp. 2192-2198 ◽  
Author(s):  
Robert P. Carson ◽  
André Diedrich ◽  
David Robertson
Keyword(s):  
Baroreflex Sensitivity ◽  
Orthostatic Intolerance ◽  
Spectral Power ◽  
Low Frequency ◽  
Sympathetic Outflow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Genetic Form ◽  
Stimulation Of

Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. We assessed the combined central and peripheral effects of pharmacological NET blockade on cardiovascular regulation and baroreflex sensitivity in rats. NE reuptake was blocked chronically in female Sprague-Dawley rats by the NET antagonist desipramine (DMI). Treated animals demonstrated an elevated supine heart rate, reduced tyramine responsiveness, and a reduced plasma ratio of the intraneuronal NE metabolite dihydroxyphenylglycol relative to NE, all of which are consistent with observations in human NET deficiency. Spectral analysis revealed a dramatic decrease in low-frequency spectral power after DMI that was consistent with decreased sympathetic outflow. Stimulation of the baroreflex with the vasodilator nitroprusside revealed an attenuated tachycardia in DMI-treated animals. This indicated that the DMI-induced sympathoinhibitory effects of increased NE in the brain stem predominates over the functional elevation of NE stimulation of peripheral targets. Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency.

scholarly journals Divergence of the feeding and thermogenic pathways influenced by NPY in the hypothalamic PVN of the rat

1998 ◽  
Vol 275 (2) ◽  
pp. R471-R477 ◽  
Author(s):  
Catherine M. Kotz ◽  
Jacqueline E. Briggs ◽  
Martha K. Grace ◽  
Allen S. Levine ◽  
Charles J. Billington
Keyword(s):  
Uncoupling Protein ◽  
Solitary Tract ◽  
Feeding Response ◽  
Sprague Dawley ◽  
Inhibitory Pathway ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Brown Adipose ◽  
Actin Mrna ◽  
Feeding Effects

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) increases feeding and decreases brown adipose tissue (BAT) uncoupling protein (UCP) and lipoprotein lipase (LPL) mRNA. Previously we reported that the feeding and BAT effects induced by NPY in the PVN are blocked by 50 μg naltrexone (NTX) in the rostral nucleus of the solitary tract (rNTS). We sought to determine whether the effect of rNTS NTX on PVN NPY-induced alterations in energy metabolism occurred at lower doses of NTX. Male Sprague-Dawley rats were fitted with cannulas into two sites: PVN and rNTS. Feeding response, BAT UCP, and LPL mRNA were measured after injection of 0, 5, 10, and 25 μg NTX in the rNTS ± 1 μg NPY in the PVN. One-hour feeding response to PVN NPY was significantly and dose dependently decreased by 10 and 25 μg rNTS NTX (−23 and −31%, respectively). However, rNTS NTX did not block the PVN NPY-induced decrease in BAT UCP or LPL mRNA. BAT β-actin mRNA (as a measure of overall changes in gene expression) was unchanged among treatment groups. These results indicate a possible divergence in the PVN NPY feeding-stimulatory/BAT-inhibitory pathway, such that PVN NPY feeding effects may be routed through the rNTS whereas BAT effects may be due to alterations at another neural site.

scholarly journals Angiotensin-(1–12) requires angiotensin converting enzyme and AT1 receptors for cardiovascular actions within the solitary tract nucleus

2010 ◽  
Vol 299 (3) ◽  
pp. H763-H771 ◽  
Author(s):  
Amy C. Arnold ◽  
Katsunori Isa ◽  
Hossam A. Shaltout ◽  
Manisha Nautiyal ◽  
Carlos M. Ferrario ◽  
...  
Keyword(s):  
Baroreflex Sensitivity ◽  
Ace Inhibitor ◽  
Pressor Response ◽  
The Novel ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sprague Dawley ◽  
Cardiovascular Actions ◽  
Sprague Dawley Rats ◽  
Spontaneous Baroreflex

The novel peptide, angiotensin (ANG)-(1–12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT1 receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1–12) can serve as a substrate for either ANG II or ANG-(1–7) formation, depending on the local tissue enzymes. Although levels of ANG-(1–12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1–12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1–12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [ n = 7; 1.06 ± 0.06 baseline vs. 0.44 ± 0.07 ms/mmHg after ANG-(1–12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response ( P < 0.05). NTS pretreatment with an AT1 receptor antagonist or ACE inhibitor prevented ANG-(1–12)-mediated autonomic and depressor responses. ANG-(1–12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1–12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1–12) is processed to ANG II for cardiovascular actions at AT1 receptors within the NTS. The lack of acute endogenous ANG-(1–12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1–12) may be activated only under hypertensive conditions.

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