Catestatin in rat RVLM is sympathoexcitatory, increases barosensitivity, and attenuates chemosensitivity and the somatosympathetic reflex

2010 ◽  
Vol 299 (6) ◽  
pp. R1538-R1545 ◽  
Author(s):  
Andrea H. Gaede ◽  
Paul M. Pilowsky
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Brain Stem ◽  
Sympathetic Nerve ◽  
Chromogranin A ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Nerve Activity ◽  
Cardiorespiratory Control ◽  
Somatosympathetic Reflex

The fundamental role and corollary effects of neuropeptides that govern cardiorespiratory control in the brain stem are poorly understood. One such regulatory peptide, catestatin [Cts, human chromogranin A-(352–372)], noncompetitively inhibits nicotinic-cholinergic-stimulated catecholamine release. Previously, we demonstrated the presence of chromogranin A mRNA in brain stem neurons that are important for the maintenance of arterial pressure. In the present study, using immunofluorescence histochemistry, we show that Cts immunoreactivity is colocalized with tyrosine hydroxylase in C1 neurons of the rostral ventrolateral medulla (RVLM, n = 3). Furthermore, we investigated the effects of Cts on resting blood pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and adaptive reflexes. Cts (1 mM in 50 nl or 100 μM in 50–100 nl) was microinjected into the RVLM in urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats ( n = 19). Cardiovascular responses to stimulation of carotid baroreceptors, peripheral chemoreceptors, and the sciatic nerve (somatosympathetic reflex) were analyzed. Cts (1 mM in 50 nl) increased resting arterial pressure (28 ± 3 mmHg at 2 min postinjection), sympathetic nerve activity (15 ± 3% at 2 min postinjection), and phrenic discharge amplitude (31 ± 4% at 10 min postinjection). Cts increased sympathetic barosensitivity 40% (slope increased from −0.05 ± 0.01 before Cts to −0.07 ± 0.01 after Cts) and attenuated the somatosympathetic reflex [1st peak: 36% (from 132 ± 32.1 to 84.0 ± 17.0 μV); 2nd peak: 44% (from 65.1 ± 21.4 to 36.6 ± 14.1 μV)] and chemoreflex (blood pressure response to anoxia decreased 55%, sympathetic response decreased 46%). The results suggest that Cts activates sympathoexcitatory bulbospinal neurons in the RVLM and plays an important regulatory role in adaptive reflexes.

Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM

2012 ◽  
Vol 302 (3) ◽  
pp. R365-R372 ◽  
Author(s):  
Andrea H. Gaede ◽  
Paul M. Pilowsky
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Phrenic Nerve ◽  
Sympathetic Nerve ◽  
Chromogranin A ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Cardiorespiratory Control

Hypertension is a major cause of morbidity. The neuropeptide catestatin [human chromogranin A-(352–372)] is a peptide product of the vesicular protein chromogranin A. Studies in the periphery and in vitro studies show that catestatin blocks nicotine-stimulated catecholamine release and interacts with β-adrenoceptors and histamine receptors. Catestatin immunoreactivity is present in the rostral ventrolateral medulla (RVLM), a key site for blood pressure control in the brain stem. Recently, we reported that microinjection of catestatin into the RVLM is sympathoexcitatory and increases barosensitivity. Here, we report the effects of microinjection of catestatin (1 mM, 50 nl) into the caudal ventrolateral medulla (CVLM) in urethane-anesthetized, bilaterally vagotomized, artificially ventilated Sprague-Dawley rats ( n = 8). We recorded resting arterial pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and measured cardiovascular homeostatic reflexes. Homeostatic reflexes were evaluated by measuring cardiovascular responses to carotid baroreceptor and peripheral chemoreceptor activation. Catestatin decreased basal levels of arterial pressure (−23 ± 4 mmHg), sympathetic nerve activity (-26.6 ± 5.7%), heart rate (−19 ± 5 bpm), and phrenic nerve amplitude (−16.8 ± 3.3%). Catestatin caused a 15% decrease in phrenic inspiratory period (Ti) and a 16% increase in phrenic expiratory period (Te) but had no net effect on the phrenic interburst interval (Ttot). Catestatin decreased sympathetic barosensitivity by 63.6% and attenuated the peripheral chemoreflex (sympathetic nerve response to brief hypoxia; range decreased 39.9%; slope decreased 30.1%). The results suggest that catestatin plays an important role in central cardiorespiratory control.

Galanin microinjection into rostral ventrolateral medulla of the rat is hypotensive and attenuates sympathetic chemoreflex

2009 ◽  
Vol 296 (4) ◽  
pp. R1019-R1026 ◽  
Author(s):  
Stephen B. G. Abbott ◽  
Paul M. Pilowsky
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Somatosympathetic Reflex

Galanin is present in neurons in the brain that are important in the control of arterial pressure, and intracisternal administration of galanin evokes hypotension, but the site of action is unknown. In urethane-anesthetized, vagotomized mechanically ventilated Sprague-Dawley rats ( n = 34), we investigated the effects of microinjecting galanin (1 mM, 50 nl, 50 pmol) into the rostral ventrolateral medulla on resting splanchnic sympathetic nerve activity, arterial pressure, heart rate, and phrenic nerve activity. Second, we determined the effect of microinjecting galanin into the rostral ventrolateral medulla on the cardiovascular response to stimulation of central and peripheral chemoreceptors, arterial baroreceptors, and the somatosympathetic reflex. Galanin caused a prolonged reduction in resting splanchnic sympathetic nerve activity (−37.0 ± 7.2% of baseline), mean arterial pressure (−17.0 ± 3.5 mmHg), and heart rate (−25.0 ± 9.1 beats/min). Galanin increased the sympathoinhibitory response to aortic depressor nerve stimulation by 51.8%, had no effect on the somatosympathetic reflex, and markedly attenuated the effect of hypercapnia and hypoxia on arterial pressure (by 65% and 92.4% of control, respectively). These results suggest a role for galanin neurotransmission in the integration of the cardiovascular responses to hypoxia, hypercapnia, and the sympathetic baroreflex in the rostral ventrolateral medulla. The data suggest that galanin may be an important peptide in the homeostatic regulation of chemosensory reflexes.

Measurement of sympathetic nerve activity in the unanesthetized rat

1989 ◽  
Vol 67 (1) ◽  
pp. 250-255 ◽  
Author(s):  
J. P. Fluckiger ◽  
G. Gremaud ◽  
B. Waeber ◽  
A. Kulik ◽  
A. Ichino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Blood Pressure Reduction ◽  
Response Curves ◽  
Nerve Activity ◽  
Dose Dependent

A new system was developed in our laboratory to continuously monitor intra-arterial pressure, heart rate, and sympathetic nerve activity in unanesthetized rats. The animals were prepared 24 h before the start of the experiments. Sympathoneural traffic was measured at the level of splanchnic nerve. The amplitude of the spikes recorded at this level was utilized to express sympathetic nerve activity. The amplitude of the residual electroneurogram signal present 30 min after the rats were killed was 32 +/- 2 mV (mean +/- SE; n = 11). For analysis, these background values were subtracted from values determined in vivo. The nerve we studied contains postganglionic fibers, since electrical activity decreased in response to ganglionic blockade with pentolinium (1.25 mg/min iv for 4 min). The amplitude of spikes fell by 43 +/- 4% (n = 4). Sympathetic nerve activity was highly reproducible at a 24-h interval (104 +/- 26 vs. 111 +/- 27 mV for the amplitude of spikes; n = 11). Dose-response curves to the alpha 1-stimulant methoxamine and to bradykinin were established in four rats. The increase in blood pressure induced by methoxamine caused a dose-dependent fall in sympathetic nerve activity, whereas the blood pressure reduction resulting from bradykinin was associated with a dose-dependent activation of sympathetic drive. These data therefore indicate that it is possible with out system to accurately measure sympathetic nerve activity in the awake rat, together with intra-arterial pressure and heart rate.

Arterial pressure and muscle sympathetic nerve activity are increased after two hours of sustained but not cyclic hypoxia in healthy humans

2005 ◽  
Vol 98 (1) ◽  
pp. 343-349 ◽  
Author(s):  
Renaud Tamisier ◽  
Amit Anand ◽  
Luz M. Nieto ◽  
David Cunnington ◽  
J. Woodrow Weiss
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Activity ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Arterial Oxygen ◽  
Nerve Activity ◽  
Arterial Blood ◽  
Sustained Hypoxia

Sustained and episodic hypoxic exposures lead, by two different mechanisms, to an increase in ventilation after the exposure is terminated. Our aim was to investigate whether the pattern of hypoxia, cyclic or sustained, influences sympathetic activity and hemodynamics in the postexposure period. We measured sympathetic activity (peroneal microneurography), hemodynamics [plethysmographic forearm blood flow (FBF), arterial pressure, heart rate], and peripheral chemosensitivity in normal volunteers on two occasions during and after 2 h of either exposure. By design, mean arterial oxygen saturation was lower during sustained relative to cyclic hypoxia. Baseline to recovery muscle sympathetic nerve activity and blood pressure went from 15.7 ± 1.2 to 22.6 ± 1.9 bursts/min ( P < 0.01) and from 85.6 ± 3.2 to 96.1 ± 3.3 mmHg ( P < 0.05) after sustained hypoxia, respectively, but did not exhibit significant change from 13.6 ± 1.5 to 17.3 ± 2.5 bursts/min and 84.9 ± 2.8 to 89.8 ± 2.5 mmHg after cyclic hypoxia. A significant increase in FBF occurred after sustained, but not cyclic, hypoxia, from 2.3 ± 0.2 to 3.29 ± 0.4 and from 2.2 ± 0.1 to 3.1 ± 0.5 ml·min−1·100 g of tissue−1, respectively. Neither exposure altered the ventilatory response to progressive isocapnic hypoxia. Two hours of sustained hypoxia increased not only muscle sympathetic nerve activity but also arterial blood pressure. In contrast, cyclic hypoxia produced slight but not significant changes in hemodynamics and sympathetic activity. These findings suggest the cardiovascular response to acute hypoxia may depend on the intensity, rather than the pattern, of the hypoxic exposure.

Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in normotensive rats

2001 ◽  
Vol 281 (2) ◽  
pp. H975-H980 ◽  
Author(s):  
Hui Xu ◽  
Gregory D. Fink ◽  
Alex Chen ◽  
Stephanie Watts ◽  
James J. Galligan
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Nerve Activity ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arterial Blood ◽  
Independent Effects ◽  
Synthase Inhibitor

The role of the sympathetic nervous system in 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol)-induced cardiovascular responses in urethane-anesthetized, normotensive rats was evaluated. Tempol caused dose-dependent (30–300 μmol/kg iv) decreases in renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), and heart rate (HR). Similar responses were obtained after sinoaortic denervation and cervical vagotomy. These responses were not blocked following treatment with the nitric oxide synthase inhibitor N G-nitro-l-arginine (2.6 mg · kg−1 · min−1 iv for 5 min) or the α2-adrenergic receptor antagonist idazoxan (0.3 mg/kg iv bolus). Idazoxan blocked the effects of clonidine (10 μg/kg iv) on HR, MAP, and RSNA. Hexamethonium (30 mg/kg iv) inhibited RSNA, and tempol did not decrease RSNA after hexamethonium. The effects of tempol on HR and MAP were reduced by hexamethonium. In conclusion, depressor responses caused by tempol are mediated, partly, by sympathoinhibition in urethane-anesthetized, normotensive rats. Nitric oxide does not contribute to this response, and the sympathoinhibitory effect of tempol is not mediated via α2-adrenergic receptors. Finally, tempol directly decreases HR, which may contribute to the MAP decrease.

PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo

2008 ◽  
Vol 294 (4) ◽  
pp. R1304-R1311 ◽  
Author(s):  
Melissa M. J. Farnham ◽  
Qun Li ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Blood Pressure ◽  
Brain Stem ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Intrathecal Administration ◽  
Ventrolateral Medulla ◽  
Cell Group ◽  
Nerve Activity ◽  
The Brain

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide present in the rat brain stem. The extent of its localization within catecholaminergic groups and bulbospinal sympathoexcitatory neurons is not established. Using immunohistochemistry and in situ hybridization, we determined the extent of any colocalization with catecholaminergic and/or bulbospinal projections from the brain stem was determined. PACAP mRNA was found in tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the C1-C3 cell groups. In the rostral ventrolateral medulla (RVLM), PACAP mRNA was found in 84% of the TH-ir neurons and 82% of bulbospinal TH-ir neurons. The functional significance of these PACAP mRNA positive bulbospinal neurons was tested by intrathecal administration of PACAP-38 in anaesthetized rats. Splanchnic sympathetic nerve activity doubled (110%) and heart rate rose significantly (19%), although blood pressure was unaffected. In addition, as previously reported, PACAP was found in the A1 cell group but not in the A5 cell group or in the locus coeruleus. The RVLM is the primary site responsible for the tonic and reflex control of blood pressure through the activity of bulbospinal presympathetic neurons, the majority of which contain TH. The results indicate 1) that pontomedullary neurons containing both TH and PACAP that project to the intermediolateral cell column originate from C1-C3 and not A5, and 2) intrathecal PACAP-38 causes a prolonged, sympathoexcitatory effect.

Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity

2000 ◽  
Vol 279 (1) ◽  
pp. H245-H249 ◽  
Author(s):  
Chester A. Ray ◽  
Dario I. Carrasco
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Voluntary Contraction ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
Muscle Ischemia

The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training ( n = 9), sham training ( n = 7), or control ( n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 ± 1 to 62 ± 1 mmHg) and mean arterial pressure (86 ± 1 to 82 ± 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 ± 3 to 113 ± 2 mmHg), heart rate (67 ± 4 to 66 ± 4 beats/min), and MSNA (14 ± 2 to 15 ± 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.

scholarly journals Hemodynamic defense response to thyrotropin-releasing hormone injected into medial preoptic nucleus in rats

1991 ◽  
Vol 261 (2) ◽  
pp. R305-R312 ◽  
Author(s):  
A. L. Siren ◽  
S. Vonhof ◽  
G. Feuerstein
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Defense Response ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic

The role of thyrotropin-releasing hormone (TRH) and glutamate in central cardiovascular control was studied by microinjections (50 nl) of these agents into the medial or median preoptic nuclei of conscious rats (n = 49) with continuous recording of mean arterial pressure, heart rate, blood flow, and vascular resistance in hindquarter, renal, and mesenteric blood vessels. In addition, the effect of TRH on renal sympathetic nerve activity was studied in anesthetized rats. TRH (2.4-240 pmol) elicited the typical hemodynamic pattern of the "defense response" consisting of increased blood pressure, tachycardia, hindquarter vasodilation, and constriction of renal and mesenteric blood vessels. Maximum changes in cardiovascular variables after the 24-pmol dose were +12 +/- 2 mmHg (mean arterial pressure), +73 +/- 15 beats/min (heart rate), -21 +/- 6% (hindquarter resistance), +15 +/- 6% (renal resistance), and +31 +/- 6% (mesenteric resistance), P less than 0.05 compared with saline. In anesthetized rats, TRH at the 2.4-pmol dose increased renal sympathetic nerve activity (greater than 200%, n = 5, P less than 0.05 compared with control) with no effect on blood pressure or renal flow. Glutamate (10 or 100 nmol) produced a similar pattern of hemodynamic changes as TRH. Peak effects after the 100-nmol dose of glutamate were +16 +/- 2 mmHg (mean arterial pressure), +57 +/- 11 beats/min (heart rate), -31 +/- 3% (hindquarter resistance), +29 +/- 9% (renal resistance), and +87 +/- 22% (mesenteric resistance), P less than 0.05 compared with saline. The glutamate N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (300 micrograms/kg iv) attenuated the pressor-tachycardic responses to TRH and the pressor-mesenteric constrictor responses to glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals 2019 Ludwig Lecture: Rhythms in sympathetic nerve activity are a key to understanding neural control of the cardiovascular system

2020 ◽  
Vol 318 (2) ◽  
pp. R191-R205 ◽  
Author(s):  
Susan M. Barman
Keyword(s):  
Brain Stem ◽  
Cardiovascular System ◽  
Sympathetic Nerve ◽  
Neural Control ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Sympathetic Nerves ◽  
Ventrolateral Medulla ◽  
Nerve Activity

This review is based on the Carl Ludwig Distinguished Lecture, presented at the 2019 Experimental Biology Meeting in Orlando, FL, and provides a snapshot of >40 years of work done in collaboration with the late Gerard L. Gebber and colleagues to highlight the importance of considering the rhythmic properties of sympathetic nerve activity (SNA) and brain stem neurons when studying the neural control of autonomic regulation. After first providing some basic information about rhythms, I describe the patterns and potential functions of rhythmic activity recorded from sympathetic nerves under various physiological conditions. I review the evidence that these rhythms reflect the properties of central sympathetic neural networks that include neurons in the caudal medullary raphe, caudal ventrolateral medulla, caudal ventrolateral pons, medullary lateral tegmental field, rostral dorsolateral pons, and rostral ventrolateral medulla. The role of these brain stem areas in mediating steady-state and reflex-induced changes in SNA and blood pressure is discussed. Despite the common appearance of rhythms in SNA, these oscillatory characteristics are often ignored; instead, it is common to simply quantify changes in the amount of SNA to make conclusions about the function of the sympathetic nervous system in mediating responses to a variety of stimuli. This review summarizes work that highlights the need to include an assessment of the changes in the frequency components of SNA in evaluating the cardiovascular responses to various manipulations as well as in determining the role of different brain regions in the neural control of the cardiovascular system.

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