scholarly journals Sedentary conditions and enhanced responses to GABA in the RVLM: role of the contralateral RVLM

2017 ◽  
Vol 313 (2) ◽  
pp. R158-R168 ◽  
Author(s):  
Maryetta D. Dombrowski ◽  
Patrick J. Mueller
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sympathetic Nerves ◽  
Ventrolateral Medulla ◽  
Sprague Dawley ◽  
Physically Active ◽  
Sprague Dawley Rats ◽  
Sympathetic Nervous ◽  
Gabaergic Modulation ◽  
Sedentary Conditions

A sedentary lifestyle is a major risk factor for cardiovascular disease, and both conditions are associated with overactivity of the sympathetic nervous system. Ongoing discharge of sympathetic nerves is regulated by the rostral ventrolateral medulla (RVLM), which in turn is modulated by the primary excitatory and inhibitory neurotransmitters glutamate and γ-amino-butyric acid (GABA), respectively. We reported previously that sedentary conditions enhance GABAergic modulation of sympathoexcitation in the RVLM, despite overall increased sympathoexcitation. Thus the purpose of this study was to test the hypothesis that sedentary conditions increase responsiveness to GABA in RVLM. Male Sprague-Dawley rats performed either chronic wheeling running or remained sedentary for 12–15 wk. Animals were instrumented to perform RVLM microinjections under Inactin anesthesia while mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SSNA) were recorded. Unilateral microinjections of GABA (30 nl, 0.3–600 mM) into the RVLM produced dose-dependent decreases in MAP and SSNA; however, no group differences were observed. Inhibition of the contralateral RVLM (muscimol, 2 mM, 90 nl) caused decreases in MAP and SSNA that were not different between groups but enhanced decreases in SSNA to GABA in sedentary rats only. In sinoaortic denervated rats, GABA microinjections before or after inhibition of the contralateral RVLM caused decreases in MAP and SSNA that were not different between groups. Our results suggest that the contralateral RVLM plays an important role in buffering responses to inhibition of the ipsilateral RVLM under sedentary but not physically active conditions. Based on these studies and others, sedentary conditions appear to enhance both sympathoinhibitory and sympathoexcitatory mechanisms in the RVLM. Enhanced sympathoinhibition may act to reduce already elevated sympathetic nervous system activity following sedentary conditions.

Abstract 291: Antihypertensive Effect Of Bia 5-1058 a New Selective Peripheral Dopamine β-hydroxylase Inhibitor

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Bruno Igreja ◽  
Nuno M Pires ◽  
Lyndon C Wright ◽  
Patrío Soares-da-Silva
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Receptor Antagonist ◽  
Antihypertensive Effect ◽  
Antihypertensive Drugs ◽  
Radio Telemetry ◽  
Sympathetic Nerves ◽  
Maximum Reduction ◽  
Sympathetic Nervous

The sympathetic nervous system can alter blood pressure by modulation of cardiac output, peripheral vascular resistance and renal function. One strategy for controlling sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH; EC 1.14.17.1 ), the enzyme that catalyses the conversion of dopamine (DA) to NE in sympathetic nerves. BIA 5-1058 is a reversible DβH inhibitor that decreases NE levels in peripheral sympathetically innervated tissues slowing down sympathetic nervous system drive, without effect in brain tissues. In freely moving SHR implanted with radio-telemetry transmitters single administration of BIA 5-1058 showed a dose (3, 30 and 100 mg/Kg) and time dependent effect on blood pressure with no significant effect on heart rate (HR) and total activity monitored over a 96-hour period. The maximum reduction on systolic blood pressure (SBP) was -10.8, -21.1 and -35.2 mmHg for 3, 30 and 100 mg/Kg, respectively and the maximum reduction on diastolic blood pressure (DBP) was -9.9, -18.4 and -24.8 mmHg for 3, 30 and 100 mg/Kg, respectively. The antihypertensive effect of BIA 5-1058 (30 mg/Kg) was further evaluated in combination with efficacious doses of well-known antihypertensive drugs, like the ACE inhibitor captopril, the AT1 receptor antagonist losartan, the diuretic hydrochlorothiazide, beta-blocker metoprolol, the alpha-1 receptor antagonist prazosin, and the calcium channel blocker diltiazem. All drugs were administered orally (single dose) in a cross-over design and the effect was monitored for 72 hours. The combination of BIA 5-1058 with any of the tested antihypertensive drugs caused a stronger and prolonged blood pressure decrease than any of the compounds alone.In conclusion, peripheral DβH inhibitors can be used, alone or in combination with others antihypertensive drugs, to reduce blood pressure.

Sympathetic regulation of cerebral blood flow during seizures in newborn lambs

1988 ◽  
Vol 255 (3) ◽  
pp. H563-H568
Author(s):  
C. D. Kurth ◽  
L. C. Wagerle ◽  
M. Delivoria-Papadopoulos
Keyword(s):  
Blood Flow ◽  
Nervous System ◽  
Cerebral Blood Flow ◽  
Sympathetic Nervous System ◽  
Sympathetic Nerves ◽  
The Other ◽  
Cerebral White Matter ◽  
Blood Flows ◽  
Sympathetic Regulation ◽  
Sympathetic Nervous

We examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs (3–11 days old) during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow (mean +/- SE ml.min-1.100 g-1) was, respectively, 12 +/- 3 (9%), 71 +/- 12 (21%), 120 +/- 15 (38%), and 54 +/- 5 (14%) greater (P less than 0.05) in the D than in the I hemibrain. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10–39% greater (P less than 0.05) in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10–31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17–27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.

scholarly journals Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

1997 ◽  
Vol 273 (2) ◽  
pp. H593-H599 ◽  
Author(s):  
H. Kobori ◽  
A. Ichihara ◽  
H. Suzuki ◽  
T. Takenaka ◽  
Y. Miyashita ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Renin Angiotensin System ◽  
Sympathetic Denervation ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sympathetic Nervous

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Vascular angiotensin and the sympathetic nervous system: do they interact?

1994 ◽  
Vol 267 (1) ◽  
pp. H187-H194 ◽  
Author(s):  
K. F. Hilgers ◽  
R. Veelken ◽  
I. Kreppner ◽  
D. Ganten ◽  
F. C. Luft ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Nerve Stimulation ◽  
High Performance ◽  
Spontaneously Hypertensive Rat ◽  
Pressor Response ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Sympathetic Nervous

We tested the hypothesis that local vascular formation of angiotensin (ANG) II and the sympathetic nervous system potentiate each other. Isolated rat hindquarters were perfused with an artificial medium, and ANG I and II release was measured by high-performance liquid chromatography and radioimmunoassay. Electrical stimulation of the lumbar sympathetic chain (0.5, 2, and 8 Hz) did not affect vascular ANG release in Sprague-Dawley (SD) rats. Hypertensive, ren-2 transgenic (TG+) rat hindquarters released significantly more ANG I (110 +/- 19 vs. 65 +/- 21 fmol/30 min in SD rats) and ANG II (235 +/- 22 vs. 140 +/- 30 fmol/30 min); however, nerve stimulation did not alter ANG release in TG+ rats. Captopril inhibited vascular ANG II release by 90%, but neither captopril nor ANG II receptor blockade by losartan affected the pressor response to nerve stimulation in SD and TG+ rats. Isoproterenol failed to increase either vascular ANG release or pressor response to nerve stimulation in SD or spontaneously hypertensive rat hindquarters. Exogenous renin, which increased vascular ANG release approximately 100-fold, prolonged the pressor responses to nerve stimulation. We conclude that the vascular renin-ANG system does not interact with the sympathetic nervous system locally. However, high concentrations of ANG II, which can be induced by circulation-derived renin, may prolong the duration of sympathetic nerve-induced vasoconstriction.

Regulation by sympathetic nervous system of accelerated growth of salivary glands of rats

1961 ◽  
Vol 201 (4) ◽  
pp. 707-710 ◽  
Author(s):  
Herbert Wells ◽  
Chester Handelman ◽  
Elliot Milgram
Keyword(s):  
Nervous System ◽  
Salivary Gland ◽  
Sympathetic Nervous System ◽  
Inferior Alveolar Nerve ◽  
Normal Growth ◽  
Sympathetic Nerves ◽  
Submandibular Salivary Gland ◽  
Lower Incisor ◽  
Accelerated Growth ◽  
Sympathetic Nervous

Although the early (24-hr) effect of unilateral extirpation of the superior cervical sympathetic ganglion is to increase the weight of the submandibular salivary gland on the operated side, ganglionectomy subsequently results in an inhibition of the normal growth of the ipsilateral submandibular gland, evident within 8 days. Prior ganglionectomy almost completely prevents the increase in weight of the ipsilateral gland which otherwise follows either amputation of the lower incisor teeth or resection of the inferior alveolar nerve. The increase in gland weight which follows a single amputation of the incisors was significantly inhibited in rats treated with reserpine or bretylium tosylate, drugs which interfere with the storage or release of norepinephrine by sympathetic nerves. It is concluded that these data support the hypothesis previously offered that the sympathetic nervous system may be involved both in the accelerated growth of the submandibular glands that follows amputation of the lower incisor teeth and in the maintenance of normal salivary gland size.

scholarly journals Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines

2020 ◽  
Vol 11 ◽  
Author(s):  
John P. Bielanin ◽  
Nerone O. Douglas ◽  
Jonathan A. Shulgach ◽  
Andrew A. McCall ◽  
Derek M. Miller ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Firing Rate ◽  
Nucleus Tractus Solitarius ◽  
Ventrolateral Medulla ◽  
Sympathetic Nervous System Activity ◽  
System Activity ◽  
Nervous System Activity ◽  
Sympathetic Nervous ◽  
Conscious Animals

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.

scholarly journals Hyperinsulinemic rats are normotensive but sensitized to angiotensin II

2008 ◽  
Vol 294 (4) ◽  
pp. R1240-R1247 ◽  
Author(s):  
Maria E. Johansson ◽  
Irene J. Andersson ◽  
Camilla Alexanderson ◽  
Ole Skøtt ◽  
Agneta Holmäng ◽  
...  
Keyword(s):  
Nervous System ◽  
Angiotensin Ii ◽  
Sympathetic Nervous System ◽  
Vascular Function ◽  
Ex Vivo ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Air Jet ◽  
Important Interaction ◽  
Sympathetic Nervous

The effect of insulin on blood pressure (BP) is debated, and an involvement of an activated renin-angiotensin aldosterone system (RAAS) has been suggested. We studied the effect of chronic insulin infusion on telemetry BP and assessed sympathetic activity and dependence of the RAAS. Female Sprague-Dawley rats received insulin (2 units/day, INS group, n = 12) or insulin combined with losartan (30 mg·kg−1·day−1, INS+LOS group, n = 10), the angiotensin II receptor antagonist, for 6 wk. Losartan-treated (LOS group, n = 10) and untreated rats served as controls ( n = 11). We used telemetry to measure BP and heart rate (HR), and acute ganglion blockade and air-jet stress to investigate possible control of BP by the sympathetic nervous system. In addition, we used myograph technique to study vascular function ex vivo. The INS and INS+LOS groups developed euglycemic hyperinsulinemia. Insulin did not affect BP but increased HR (27 beats/min on average). Ganglion blockade reduced mean arterial pressure (MAP) similarly in all groups. Air-jet stress did not increase sympathetic reactivity but rather revealed possible blunting of the stress response in hyperinsulinemia. Chronic losartan markedly reduced 24-h-MAP in the INS+LOS group (−38 ± 1 mmHg P < 0.001) compared with the LOS group (−18 ± 1 mmHg, P ≤ 0.05). While insulin did not affect vascular function per se, losartan improved endothelial function in the aorta of insulin-treated rats. Our results raise doubt regarding the role of hyperinsulinemia in hypertension. Moreover, we found no evidence that insulin affects sympathetic nervous system activity. However, chronic losartan treatment revealed an important interaction between insulin and RAAS in BP control.

scholarly journals Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines

2020 ◽  
Author(s):  
John P. Bielanin ◽  
Nerone O. Douglas ◽  
Jonathan A. Shulgach ◽  
Andrew A. McCall ◽  
Derek M. Miller ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Firing Rate ◽  
Nucleus Tractus Solitarius ◽  
Ventrolateral Medulla ◽  
Sympathetic Nervous System Activity ◽  
System Activity ◽  
Nervous System Activity ◽  
Sympathetic Nervous ◽  
Conscious Animals

AbstractConsiderable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF neurons and RVLM was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal’s vigilance and alertness.

TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3

2008 ◽  
Vol 294 (1) ◽  
pp. C306-C312 ◽  
Author(s):  
Deborah H. Damon
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Function ◽  
Important Determinant ◽  
Sympathetic Neurons ◽  
Sympathetic Nerves ◽  
Sympathetic Control ◽  
Neurotrophin 3 ◽  
Sympathetic Nervous

The sympathetic nervous system is an important determinant of vascular function. The effects of the sympathetic nervous system are mediated via release of neurotransmitters and neuropeptides from postganglionic sympathetic neurons. The present study tests the hypothesis that vascular smooth muscle cells (VSM) maintain adrenergic neurotransmitter/neuropeptide expression in the postganglionic sympathetic neurons that innervate them. The effects of rat aortic and tail artery VSM (AVSM and TAVSM, respectively) on neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were assessed in cultures of dissociated sympathetic neurons. AVSM decreased TH (39 ± 12% of control) but did not affect NPY. TAVSM decreased TH (76 ± 10% of control) but increased NPY (153 ± 20% of control). VSM expressed leukemia inhibitory factor (LIF) and neurotrophin-3 (NT-3), which are known to modulate NPY and TH expression. Sympathetic neurons innervating blood vessels expressed LIF and NT-3 receptors. Inhibition of LIF inhibited the effect of AVSM on TH. Inhibition of neurotrophin-3 (NT-3) decreased TH and NPY in neurons grown in the presence of TAVSM. These data suggest that vascular-derived LIF decreases TH and vascular-derived NT-3 increases or maintains NPY and TH expression in postganglionic sympathetic neurons. NPY and TH in vascular sympathetic nerves are likely to modulate NPY and/or norepinephrine release from these nerves and are thus likely to affect blood flow and blood pressure. The present studies suggest a novel mechanism whereby VSM would modulate sympathetic control of vascular function.

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