Stimulation of dog RVLM and A5 area changes sympathetic outflow to vascular beds without effect on the heart

Studies were conducted in anesthetized, vagotomized dogs while blood pressure; blood flows in femoral, renal, mesenteric, and left circumflex coronary arteries; electrocardiogram; and regional cardiac contractile force were monitored. The ventral surface of the medulla was exposed, and pressor sites in the rostral ventrolateral medulla (RVLM) were mapped by microinjections of L-glutamate. L-Glutamate activation of the RVLM evoked selective effects on different components of the cardiovascular system. Increases of 20-130 mmHg in blood pressure were accompanied by vascular conductance decreases in the femoral (-48 +/- 4%), renal (-30 +/- 4%), and mesenteric (-38 +/- 3%) arterial beds. These effects were without any obvious topography within the RVLM. There were only small or negligible changes in heart rate (HR), cardiac contractile force, and coronary vascular conductance. Thus stimulation of the canine RVLM increased sympathetic tone selectively to structures other than the heart. Stimulation of the ventral medulla in a region that lay rostral to the RVLM and ventromedial to the facial nucleus selectively increased femoral vascular conductance by 103 +/- 33% and decreased vascular conductance in the renal (-20 +/- 5%) and mesenteric (-15 +/- 4%) arterial beds. There was no increase in HR, and the increases in blood pressure were relatively small. Immunohistochemical data led us, tentatively, to identify this rostral area as overlapping part of the A5 area.

Prolongation in expiration evoked from ventrolateral pons of adult rats

Jodkowski, Józef S., Sharon K. Coles, and Thomas E. Dick. Prolongation in expiration evoked from ventrolateral pons of adult rats. J. Appl. Physiol. 82(2): 377–381, 1997.—Activation of neurons in the ventrolateral (vl) pons was hypothesized to alter the breathing pattern because previous studies demonstrated apneusis after inhibiting neuronal activity with bilateral muscimol (10 mM) microinjections into the vl pons (17). The excitatory amino acid l-glutamate (10 mM) was microinjected (10–100 nl) into the vl pons in anesthetized, vagotomized, paralyzed, and ventilated adult rats ( n = 8). In four of these animals, the target site was approached from the ventral surface of the pons to avoid penetrating the dorsolateral (dl) pons. The expiratory phase was prolonged transiently and concurrently with the microinjection. The location of the injection sites included the A5 area, was independent of the approach, and was distinct from the dl pons. These results complement our previous data and indicate that neurons located in the vl pons influence respiration specifically by prolonging expiration when activated and by delaying the inspiratory-to-expiratory phase transition when inhibited.

A5 noradrenergic neurons and the carotid sympathetic chemoreflex

Inhibition of neural activity in the caudal ventrolateral pons (A5 area) by microinjection of muscimol (Mus) attenuates (-65%) the carotid sympathetic chemoreflex (SChR) without altering the concomitant activation of the phrenic nerve (PND). The present study, performed in urethan-anesthetized rats, explores the possibility that activation of the noradrenergic (NE) neurons of the A5 area is involved in the SChR. The NE neuron-selective toxin 6-hydroxydopamine (6-OHDA) was microinjected bilaterally into the spinal cord at T2 level (4 micrograms). This dose reduced the SChR by 55% (n = 5) 90 min after injection, while 0.4 microgram of 6-OHDA produced no effect (n = 5). In seven rats that had received 250 micrograms 6-OHDA intracisternally 2 wk before, Mus injections into the A5 area failed to attenuate the SChR. These rats also had a lower resting mean arterial pressure than controls (97 vs. 112 mmHg). Spinal intrathecal injection of alpha-adrenergic receptor antagonists (prazosin, 10 and 20 micrograms) or phentolamine (20 and 40 micrograms) attenuated resting sympathetic nerve discharge (SND) and SChR in a roughly proportional manner (25-40%); the beta-adrenergic antagonist nadolol (10 and 20 microgram(s) intrathecally) attenuated the SChR selectively but modestly (-10%). The results are generally compatible with the hypothesis that A5 NE neurons and particularly their spinal cord projection could play a facilitating role in the SChR. However, clear evidence that A5 cells contribute selectively to sympathoactivation during chemoreceptor stimulation by releasing NE in the spinal cord could not be obtained.

Splanchnic nerve response to A5 area stimulation in rats

Microinjection of the excitatory amino acid N-methyl-D-aspartate (NMDA, 0.5 nmol) into ventrolateral pons (the A5 area) of halothane-anesthetized, paralyzed rats increased splanchnic (sSND) and renal sympathetic nerve discharges (approximately 45%) and usually decreased lumbar SND. These effects were accompanied by 1) regionally specific changes in vascular resistances, 2) an increase in the gain of the sympathetic baroreflex, and 3) modest reductions in blood pressure and heart rate. sSND activation was greatest when NMDA injections were made in the vicinity of A5 noradrenergic (NE) cells. Injection of 6-hydroxydopamine (6-OH-DA) into A5 area (after 15 days) destroyed 83% of NE neurons and reduced NMDA activation of sSND by 76%. Stimulation of sSND by NMDA in A5 area was reduced 1) 1-2 h after bilateral intraspinal injection of 6-OHDA, but not vehicle or 5,7-dihydroxytryptamine, and 2) by administration of prazosin [alpha 1-NE receptor antagonist, 1 mg/kg iv or 10-20 micrograms intrathecal (it)], but not by idazoxan (alpha 2-NE receptor antagonist, 10-20 micrograms it) or propranolol (0.2 mg/kg iv). We conclude that A5 NE cells have a visceral vasomotor sympathoexcitatory function mediated in large part by their spinal projection.

A5 noradrenergic unit activity and sympathetic nerve discharge in rats

Unit recording experiments were designed to determine whether A5 noradrenergic neurons contribute to the generation of the splanchnic sympathetic nerve discharge (SSND) of halothane-anesthetized rats. Neurons (presumed A5 cells) were selected on the following bases: location in the ventrolateral tegmentum rostrolateral to facial nucleus (FN), antidromic (AD) activation from thoracic spinal cord, and complete inhibition by clonidine (10-15 micrograms/kg iv). These cells (n = 59) had low rates of spontaneous firing (1.4 +/- 0.2 spikes/s) and slow conduction velocities (2.6 +/- 0.2 m/s). The AD activation of seven of eight neurons was abolished within 1 h after intraspinal microinjection of 6-hydroxydopamine (4 micrograms), but the drug failed to affect the AD responses of eight sympathoexcitatory cells located caudal to the FN (control cells). The terminal fields of 16 A5 area neurons were found in the intermediolateral cell column of the spinal cord. Most neurons (63%, 37/59) were inhibited by raising arterial pressure and by train stimulation of the aortic depressor nerve (ADN, 47%, 9/20). A few cells responded to ADN stimulation but not to arterial pressure elevation or vice versa. The discharge of the cells was correlated to the SSND and preceded a peak of SSND by 69 +/- 6 ms (12/29 in intact and 3/9 in debuffered rats). We conclude that 40% of A5 cells may have a visceral vasomotor sympathoexcitatory function.