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.

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.

Dorsomedial medulla is more susceptible than rostral ventrolateral medulla to hypoxic insult in cats

2001 ◽  
Vol 90 (1) ◽  
pp. 248-260 ◽  
Author(s):  
Ling-Zong Hong ◽  
Jon-Son Kuo ◽  
Mao-Hsiung Yen ◽  
Chok-Yung Chai
Keyword(s):  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Systemic Arterial Pressure ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Pressor Responses ◽  
Norepinephrine Depletion ◽  
Vertebral Nerve

We investigated the responses of systemic arterial pressure and vertebral sympathetic nerve activity to glutamate microinjections (0.1 M, 70 nl) in the dorsomedial (DM) and the rostral ventrolateral medulla (RVLM) before hypoxia and after reoxygenation (posthypoxia) after various degrees of hypoxia in anesthetized cats. Hypoxia was produced by ventilating 5% O2 and 95% N2 for different durations (hypoxia I-III). In intact cats, the glutamate-induced systemic arterial pressure and vertebral nerve activity responses of the DM were depressed after all degrees of hypoxia. Posthypoxic depression in the RVLM, however, was not observed until hypoxia II and III. Precollicular decerebration prevented depression in the RVLM, but, for the DM, it was effective only for hypoxia I. Baro- and chemoreceptor denervation abolished all posthypoxic depression in both the DM and the RVLM. Pressor responses to tyramine (100–400 μg/kg iv) remained unchanged after all degrees of hypoxia. These results suggest that the DM is more susceptible to hypoxia than the RVLM. The peripheral baro- and chemoreceptors and the suprapontine structures apparently play an important role in posthypoxic depression. Moreover, the depression is not due to the postganglionic norepinephrine depletion.

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.

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.

scholarly journals Hypertension in Patients with Neurovascular Compression Is Associated with Increased Central Sympathetic Outflow

2002 ◽  
Vol 13 (1) ◽  
pp. 35-41
Author(s):  
Hans P. Schobel ◽  
Helga Frank ◽  
Ramin Naraghi ◽  
Helmut Geiger ◽  
Elmar Titz ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cold Pressor Test ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Neurovascular Compression ◽  
Sympathetic Outflow ◽  
Nerve Activity ◽  
Central Sympathetic Outflow

ABSTRACT. Recent data suggest a causal relationship between essential hypertension and neurovascular compression (NVC) at the rostral ventrolateral medulla. An increase of central sympathetic outflow might be an underlying pathomechanism. The sympathetic nerve activity to muscle was recorded in 21 patients with hypertension with NVC (NVC+ group) and in 12 patients with hypertension without NVC (NVC− group). Heart rate variability, respiratory activity, BP, and central venous pressure at rest and during unloading of cardiopulmonary baroreceptors with lower-body negative pressure and during a cold pressor test were also measured. Resting sympathetic nerve activity to muscle was twice as high in the NVC+ group compared with the NVC− group (34 ± 22 versus 18 ± 6 bursts/min; P < 0.05). Resting heart rate (P = 0.06) and low- to high-frequency power ratio values (P = NS) (as indicators of cardiac sympathovagal balance) tended to be augmented as well in the NVC+ group. The sympathetic nerve activity to muscle response to the cold pressor test was increased in the NVC+ group versus the NVC− group (+15 ± 11 versus 6 ± 12 bursts/min; P = 0.05), but hemodynamic and sympathetic nerve responses to lower-body negative pressure did not differ between the two groups. It is concluded that NVC of the rostral ventrolateral medulla in patients with essential hypertension is accompanied by increased central sympathetic outflow. Therefore, these data support the hypothesis described in the literature: in a subgroup of patients, essential hypertension might be causally related to NVC of the rostral ventrolateral medulla, at least in part, via an increase in central sympathetic outflow.

scholarly journals Adrenomedullin increases cardiac sympathetic nerve activity in normal conscious sheep

2005 ◽  
Vol 187 (2) ◽  
pp. 275-281 ◽  
Author(s):  
C J Charles ◽  
D L Jardine ◽  
M G Nicholls ◽  
A M Richards
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Vehicle Control ◽  
Cardiac Sympathetic Nerve ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

The sympathetic nervous system and adrenomedullin (AM) both participate in the regulation of cardiac and circulatory function but their interaction remains uncertain. We have examined the effects of AM on cardiac sympathetic nerve activity (CSNA) and hemodynamics and contrasted these effects with pressure-matched nitro-prusside (NP) administration in normal conscious sheep. Compared with vehicle control, arterial pressure fell similarly with AM (P=0.04) and NP (P<0.001). Heart rate rose in response to both AM (P<0.001) and NP (P=0.002) but the rise with AM was significantly greater than that induced by NP (P<0.001). Cardiac output increased in response to AM compared with both control and NP (both P<0.001). CSNA burst frequency (bursts/min) were increased in response to both AM (P<0.001) and NP (P=0.005) with the rise in burst frequency being greater with AM compared with NP (P<0.001). CSNA burst area/min was also raised by both AM (P=0.03) and NP (P=0.002) with a trend for burst area being greater with AM than NP (P=0.07). CSNA burst incidence (bursts/100 beats) showed no significant differences between any treatment day. In conclusion, we have demonstrated that AM is associated with a greater increase in CSNA and heart rate for a given change in arterial pressure than seen with the classic balanced vasodilator NP.

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.

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