Differentiation of two cardiovascular regions within caudal ventrolateral medulla

The caudal ventrolateral medulla (CVLM) plays a significant role in the regulation of sympathetic nerve activity (SNA) and arterial pressure; however, the use of lesions to examine its role in mediating baroreceptor reflex control of SNA has yielded discrepant results. We hypothesize that this may have arisen from anatomic segregation of neurons within the CVLM that subserve different functions in sympathetic control. Thus we used microinjections of the excitotoxic agent kainic acid (200 pmol in 20 nl) to determine the effects of inactivation of neuronal cell bodies in a rostral and a caudal subregion of the CVLM on SNA, arterial pressure, and baroreceptor reflex function in urethan-anesthetized rats. Interruption of neuronal activity in the rostral CVLM (sites from 0.6 mm caudal to 0.5 mm rostral to the rostral border of the lateral reticular nucleus) elevated SNA (post-kainic acid 214% of control) and arterial pressure (+34 mmHg) and eliminated the inhibition of splanchnic SNA evoked by either aortic nerve stimulation or the pressor response to intravenous norepinephrine. In addition, the cardiac-related component of spontaneous SNA was abolished as judged from post-R wave averages and from power spectral analysis. In contrast, although a similar disruption of neuronal activity in the caudal CVLM (sites 0.0-0.6 mm rostral to the caudal border of the lateral reticular nucleus) produced a comparable increase in spontaneous SNA (post-kainic acid 196% of control) and arterial pressure (+20 mmHg), it was without effect on the ability of the baroreceptor reflex to inhibit SNA, and it enhanced the synchronization of the spontaneous bursts in SNA to the cardiac cycle. Our results suggest an organization of the CVLM in which neurons in its rostral portion are required for an effective baroreceptor reflex, whereas those in the caudal CVLM serve to limit SNA and blood pressure independent of the baroreceptor reflex.

Download Full-text

Baro-Activated Neurons With Pulse-Modulated Activity in the Rat Caudal Ventrolateral Medulla Express GAD67 mRNA

Journal of Neurophysiology ◽

10.1152/jn.00737.2002 ◽

2003 ◽

Vol 89 (3) ◽

pp. 1265-1277 ◽

Cited By ~ 68

Author(s):

Ann M. Schreihofer ◽

Patrice G. Guyenet

Keyword(s):

Tyrosine Hydroxylase ◽

Arterial Pressure ◽

Motor Neurons ◽

Choline Acetyltransferase ◽

Baroreceptor Reflex ◽

Rostral Ventrolateral Medulla ◽

Gabaergic Neurons ◽

Ventrolateral Medulla ◽

Multiple Targets ◽

Caudal Ventrolateral Medulla

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are believed to mediate the sympathetic baroreceptor reflex by inhibiting presympathetic neurons in the rostral ventrolateral medulla (RVLM). Accordingly, some CVLM neurons are activated by increased arterial pressure (AP; baro-activated), have activity strongly modulated by the AP pulse (pulse-modulated), and can be antidromically activated from the RVLM. This study examined whether baro-activated, pulse-modulated CVLM neurons are indeed GABAergic and examined their structures. We recorded extracellularly from 19 baro-activated, pulse-modulated CVLM neurons in chloralose-anesthetized rats. Most of these cells (13/19) were silenced by decreasing AP with nitroprusside, but some (6/19) remained active at low AP levels. They were also excited by phenyl biguanide (17/17) but inhibited by noxious tail pinch (8/11). Twelve baro-activated cells were filled with biotinamide and examined for expression of GAD67 mRNA. Because adjacent vagal motor neurons are also activated by increased AP, we examined choline acetyltransferase (ChAT) immunoreactivity. Most baro-activated cells (9/12) expressed high levels of GAD67 mRNA, the rest (3/12) displayed lower levels of GAD67 mRNA, but none showed ChAT immunoreactivity. In contrast, adjacent baro-inhibited CVLM cells had no GAD67 mRNA ( n = 5) but were instead tyrosine hydroxylase immunoreactive ( n = 7). Reconstruction of baro-activated CVLM neurons revealed axons that projected dorsomedially and rostrally with several axon collaterals. These data demonstrate the existence of GABAergic CVLM neurons with the physiological characteristics expected of interneurons that mediate the sympathetic baroreceptor reflex. In addition, baro-activated GABAergic CVLM neurons appear to integrate several types of inputs and provide inhibition to multiple targets.

Download Full-text

Mechanisms of pressor response produced by stimulation of nucleus ambiguus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.259.5.r955 ◽

1990 ◽

Vol 259 (5) ◽

pp. R955-R962

Author(s):

B. H. Machado ◽

M. J. Brody

Keyword(s):

Arterial Pressure ◽

Vascular Resistance ◽

Pressor Response ◽

Nucleus Ambiguus ◽

Ventrolateral Medulla ◽

Pressor Responses ◽

Regional Vascular Resistance ◽

Parasympathetic Control ◽

Renal Vascular ◽

Stimulation Of

We showed previously that activation of nucleus ambiguus (NA) induced bradycardia and increased arterial pressure. In this study, we compared responses produced by electrical and chemical (glutamate) stimulation of NA and adjacent rostral ventrolateral medulla (RVLM). Equivalent pressor responses were elicited from both areas. However: 1) The response from RVLM was elicited at a lower frequency. 2) Regional vascular resistance changes were different, i.e., electrical stimulation of NA increased vascular resistance in hindquarters much more than the renal and mesenteric beds. In contrast, electrical and chemical stimulation of RVLM produced a more prominent effect on the renal vascular bed. 3) Bradycardia was elicited from NA at lower current intensity. 4) Glutamate produced bradycardia only when injected into NA. Studies in rats with sinoaortic deafferentation showed that bradycardic response to activation of NA was only partly reflex in origin. We conclude that 1) NA and RVLM control sympathetic outflow to regional vascular beds differentially and 2) the NA region involves parasympathetic control of heart rate and sympathetic control of arterial pressure.

Download Full-text

Renal and somatic input to spinal neurons antidromically activated from the ventrolateral medulla

Journal of Neurophysiology ◽

10.1152/jn.1988.60.6.1967 ◽

1988 ◽

Vol 60 (6) ◽

pp. 1967-1981 ◽

Cited By ~ 14

Author(s):

W. S. Ammons

Keyword(s):

Reticular Formation ◽

Receptive Fields ◽

Ventrolateral Medulla ◽

Reticular Nucleus ◽

Lateral Reticular Nucleus ◽

Spinal Neurons ◽

C Fiber ◽

Somatic Input ◽

Fiber Stimulation ◽

Stimulation Of

1. Studies were done to characterize responses of spinal neurons backfired from the ventrolateral medulla to renal and somatic stimuli. Experiments were performed on 31 cats that were anesthetized with alpha-chloralose. Sixty-six spinal neurons were antidromically activated from the area of the lateral reticular nucleus or the ventrolateral reticular formation just rostral to the lateral reticular nucleus contralateral to the recording site. These cells could not be backfired from the medial reticular formation or from the spinothalamic tract just caudal to the thalamus. 2. Cells were located in laminae I, V, and VII of the T12-L2 segments. Antidromic conduction velocities averaged 35.9 +/- 7.2 m/s. Conduction velocities were unrelated to the projection site or laminar location of the cells. Termination sites of 21 cells were located in antidromic mapping experiments. Terminals were localized to the ventrolateral reticular formation, including the lateral reticular nucleus. 3. Responses to electrical stimulation of the renal nerves were always excitatory. Stimulation of renal A-delta-fibers excited 33 cells. These cells failed to respond to stimulation of renal C-fibers. The other 33 cells responded to both A-delta- and C-fiber stimulation. Latencies to A-delta-fiber stimulation averaged 9 +/- 2 ms, whereas latencies to C-fiber stimulation averaged 57 +/- 10 ms. 4. Renal mechanoreceptors were activated by occlusion of the renal vein or upper portion of the ureter. Renal vein occlusion excited 14 of 32 cells tested. Activity increased from 6 +/- 2 to 14 +/- 4 spike/s. Ureteral occlusion increased activity of 19 of 32 cells from 7 +/- 2 to 16 +/- 5 spikes/s. Cells responding to one of the mechanical stimuli were significantly more likely to receive A-delta-and C-fiber input compared with nonresponding cells. Nonresponders were more likely than responders to receive only A-delta input. 5. All cells received somatic input in addition to renal input. Twelve cells were classified as wide dynamic range, 46 as high threshold, and 8 as Deep. Somatic receptive fields most often included skin and muscle of the left flank and abdomen. Thirty-two cells had bilateral receptive fields, and 22 had inhibitory fields in addition to excitatory fields. 6. These data show that spinal neurons projecting to the ventrolateral medulla receive convergent inputs from the kidney and somatic structures. These cells may participate in a variety of functions including autonomic reflexes of renal origin.

Download Full-text

Effects of hypoxia, hyperoxia and hypercapnia on graded cerebral ischemic responses in rabbits

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.263.6.h1839 ◽

1992 ◽

Vol 263 (6) ◽

pp. H1839-H1846

Author(s):

T. Takeuchi ◽

J. Horiuchi ◽

N. Terada ◽

M. Nagao ◽

H. Terajima

Keyword(s):

Blood Flow ◽

Cerebral Ischemia ◽

Arterial Pressure ◽

Internal Carotid ◽

Pressor Response ◽

Ventrolateral Medulla ◽

Left Internal Carotid Artery ◽

Renal Nerve ◽

Tissue Po2 ◽

Cerebral Ischemic

This study was designed to determine how several factors interact to modify the cerebral ischemic pressor response (CIR) in anesthetized rabbits. After the carotid sinus and aortic nerves were bilaterally sectioned, blood flow through the left internal carotid artery (ICF), which was surgically restricted as the sole route of blood supply to the brain, was reduced by a servo-controller during ventilation with room air, and 8% and 90% O2 and 2 and 5% CO2 gas mixtures. Blood flow (MBF), tissue PO2, PCO2, and interstitial pH were measured in the rostral ventrolateral medulla. Internal carotid arterial pressure, tissue PO2, and MBF decreased proportionately as ICF decreased in the range from 4 to 0 ml/min. Hypoxia significantly increased the rise in renal nerve activity (RNA) and CIR caused by cerebral ischemia, while hyperoxia significantly decreased them. Hypercapnia had almost no influence on the increases in RNA and mean arterial pressure produced by cerebral ischemia. CIR showed a much higher correlation with changes in tissue PO2 than with the other factors. We examined how these factors interact to modify CIR and found that central hypoxia is the main factor in producing CIR.

Download Full-text

Effects of kainic acid administered to the caudal ventrolateral medulla on arterial blood pressure in the spontaneously hypertensive and normotensive Wistar-Kyoto rats

Neuroscience Letters ◽

10.1016/0304-3940(95)12226-5 ◽

1996 ◽

Vol 202 (3) ◽

pp. 145-148 ◽

Cited By ~ 5

Author(s):

Z. Yang ◽

Y.S. Chan ◽

T.M. Wong

Keyword(s):

Blood Pressure ◽

Kainic Acid ◽

Arterial Blood Pressure ◽

Ventrolateral Medulla ◽

Spontaneously Hypertensive ◽

Caudal Ventrolateral Medulla ◽

Wistar Kyoto Rats ◽

Arterial Blood ◽

Wistar Kyoto

Download Full-text

Hypotensive effect of ANG II and ANG-(1–7) at the caudal ventrolateral medulla involves different mechanisms

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00580.2001 ◽

2002 ◽

Vol 283 (5) ◽

pp. R1187-R1195 ◽

Cited By ~ 31

Author(s):

A. C. Alzamora ◽

R. A. S. Santos ◽

M. J. Campagnole-Santos

Keyword(s):

Nitric Oxide ◽

Arterial Pressure ◽

Specific Inhibitor ◽

Hypotensive Effect ◽

Ventrolateral Medulla ◽

Ang Ii ◽

Caudal Ventrolateral Medulla ◽

Before And After ◽

Male Wistar Rats ◽

Vascular Tonus

The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1–7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1–7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methyl-atropine, 2.5 mg/kg; 2) prazosin, 25 μg/kg; 3) the nitric oxide synthase (NOS) inhibitor, N G-nitro-l-arginine methyl ester (l-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1–7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; −11 ± 1 mmHg, n = 12 and −10 ± 1 mmHg, n= 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1–7) was abolished after treatment with methyl-atropine (−3 ± 0.6 mmHg, n = 9) or l-NAME (−2.3 ± 0.5 mmHg, n = 8) or 7-NI (−2.8 ± 0.6 mmHg, n = 5). In contrast, these treatments did not significantly interfere with the ANG II effect (−10 ± 2.6 mmHg, n = 8; −8 ± 1.5 mmHg, n = 8; and −12 ± 3.6 mmHg, n = 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1–7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1–7) also involves a nitric oxide-related mechanism.

Download Full-text