Differential baroreflex control of sympathetic drive by angiotensin II in the nucleus tractus solitarii

Microinjection of angiotensin II into the nucleus tractus solitarii attenuates the baroreceptor reflex-mediated bradycardia by inhibiting both vagal and cardiac sympathetic components. However, it is not known whether the baroreflex modulation of other sympathetic outputs (i.e., noncardiac) also are inhibited by exogenous angiotensin II (ANG II) in nucleus tractus solitarii (NTS). In this study, we determined whether there was a difference in the baroreflex sensitivity of sympathetic outflows at the thoracic and lumbar levels of the sympathetic chain following exogenous delivery of ANG II into the NTS. Experiments were performed in two types of in situ arterially perfused decerebrate rat preparations. Sympathetic nerve activity was recorded from the inferior cardiac nerve, the midthoracic sympathetic chain, or the lower thoracic-lumbar sympathetic chain. Increases in perfusion pressure produced a reflex bradycardia and sympathoinhibition. Microinjection of ANG II (500 fmol) into the NTS attenuated the reflex bradycardia (57% attenuation, P < 0.01) and sympathoinhibition of both the inferior cardiac nerve (26% attenuation, P < 0.05) and midthoracic sympathetic chain (37% attenuation, P < 0.05) but not the lower thoracic-lumbar chain ( P = 0.56). We conclude that ANG II in the nucleus tractus solitarii selectively inhibits baroreflex responses in specific sympathetic outflows, possibly dependent on the target organ innervated.

Cardiac sympathetic premotor neurons

To locate premotor neurons controlling the cardiac sympathetic supply and to determine their relation to brain stem vasomotor pathways, the rostral ventrolateral medulla (RVLM) was mapped in seven chloralose-anesthetized cats, with the use of microinjections of sodium glutamate (5-10 nl, 0.1 M) to excite neuronal cell bodies. Cardiac sympathetic responses were recorded from the ipsilateral inferior cardiac nerve, while recordings were made simultaneously from postganglionic vasoconstrictor fibers to skeletal muscle (ipsilateral peroneal nerve). Baroreceptors were denervated to eliminate the reflex effects of blood pressure changes. Most of the 115 injected RVLM sites excited both sympathetic nerves. Inferior cardiac nerve activity increased by up to 395% (mean 105 +/- 86%, SD), and muscle vasoconstrictor activity increased by up to 487% (110 +/- 107%). Their relative response varied with injection site, however. For 16 of the most rostromedial injections, the inferior cardiac nerve-to-muscle vasoconstrictor response ratio exceeded that expected by two- to sevenfold; for 9 very caudolateral injections that ratio was strongly reversed, favoring muscle vasoconstrictors by two to fivefold. Intervening sites gave more equal responses. Overall, the response ratio varied systematically with injection site. These findings demonstrate that neurons with preferential or selective actions on the cardiac sympathetic outflow are present in the RVLM and are organized topographically. The simplest interpretation is that a population of selective cardiac sympathetic premotor neurons occupies a territory substantially overlapping, but centered rostromedially to, the population controlling vasoconstriction in muscle.

Synchronization of cardiac-related discharges of sympathetic nerves with inputs from widely separated spinal segments

We used phase spectral analysis to study the relationships between the cardiac-related discharges of pairs of postganglionic sympathetic nerves in urethan-anesthetized or decerebrate cats. Phase angle when converted to a time interval should equal the difference in conduction times from the brain to the nerves (i.e., transportation lag) if their cardiac-related discharges have a common central source. Transportation lag was estimated as the difference in the onset latencies of activation of the nerves by electrical stimulation of the medulla or cervical spinal cord. The phase angle for the cardiac-related discharges of two nerves was not always equivalent in time to the transportation lag. For example, in some cases the cardiac-related discharges of the renal nerve were coincident with or led those of the inferior cardiac nerve. In contrast, the electrically evoked responses of the renal nerve lagged those of the inferior cardiac nerve by > or = 32 ms. These observations are consistent with a model of multiple and dynamically coupled brain stem generators of the cardiac-related rhythm, each controlling a different sympathetic nerve or exerting nonuniform influences on different portions of the spinal sympathetic outflow.

Caudal ventrolateral medullary neurons are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge

1. This is the first study to show that caudal ventrolateral medullary (CVLM) neurons play an important role in governing the 10-Hz rhythm in sympathetic nerve discharge (SND). Spike-triggered averaging showed that the naturally occurring discharges of 66 of 246 CVLM neurons located 0–2.5 mm rostral to the obex, 4–4.25 mm lateral to the midline, and within 2 mm of the ventral surface were correlated to the 10-Hz rhythm in inferior cardiac SND of 17 urethan-anesthetized cats. 2. Frequency domain analysis was used to characterize further the relationships between SND and the discharges of 45 CVLM neurons with activity correlated to the 10-Hz rhythm in inferior cardiac nerve activity. The autospectra of the discharges of 22 of these neurons contained a sharp peak near 10 Hz (corresponding to the peak in the autospectra of SND), although the mean firing rate of these neurons was only 5.9 +/- 0.5 (SE) spikes/s. The peak coherence value relating the 10-Hz discharges of these CVLM neurons and the inferior cardiac nerve was 0.42 +/- 0.03. The autospectra for the other 23 CVLM neurons did not contain a peak near 10 Hz. Their mean firing rate was 2.3 +/- 0.5 spikes/s, and the peak coherence value relating their discharges to the 10-Hz rhythm in SND was 0.08 +/- 0.01. The coherence value was significantly different than zero in all but three cases. 3. Importantly, spike-triggered averaging and coherence analysis demonstrated that CVLM neurons with activity correlated to the 10-Hz rhythm did not have activity correlated 1:1 to the cardiac-related rhythm in SND of baroreceptor-innervated cats. Also, their discharges were not correlated to the irregular 2- to 6-Hz oscillations in SND of baroreceptor-denervated cats. These data support the hypothesis that different pools of brain stem neurons generate the 10-Hz rhythm and the 2- to 6-Hz oscillations (or cardiac-related rhythm) in SND. 4. Despite the fact that CVLM neurons with activity correlated to the 10-Hz rhythm did not have activity correlated 1:1 to the cardiac-related rhythm in SND, these neurons were influenced by baroreceptor afferent nerve activity. First, their firing rates could be decreased (n = 12) or increased (n = 2) during the pressor response induced by inflating a balloon in the aorta (aortic obstruction). Second, on occasion, the discharges of CVLM neurons and the 10-Hz rhythm in SND were entrained to a harmonic of the heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

The 10-Hz sympathetic rhythm is dependent on raphe and rostral ventrolateral medullary neurons

We studied the effects of brain stem and spinal lesions on the 10-Hz rhythms in left and right inferior cardiac sympathetic nerve discharge (SND) of baroreceptor-denervated, decerebrate cats. Unilateral medullary lesions [parasagittal section 1.5 mm lateral to midline, radiofrequency lesion of the rostral ventrolateral medulla (RVLM), or chemical inactivation (muscimol) of the RVLM] dramatically reduced the 10-Hz rhythmic discharges in the two nerves. Power in the 10-Hz band of ipsilateral inferior cardiac SND was reduced more than that in contralateral SND. In contrast, bilateral parasagittal medullary sections or microinjection of muscimol into the medullary raphe uniformly reduced the 10-Hz rhythmic discharges of both nerves. Unlike unilateral medullary lesions, rostral pontine or cervical spinal hemisection reduced the 10-Hz discharges of only the ipsilateral inferior cardiac nerve. The chemical inactivation experiments demonstrate that the 10-Hz rhythm in SND is dependent on medullary raphe and RVLM neurons. Moreover the experiments with unilateral lesions demonstrate a mutually facilitatory interaction of medullary circuits that are responsible for the 10-Hz rhythmic discharges in sympathetic nerves located on opposite sides of the body.

GABA-mediated inhibition of sympathoexcitatory neurons by midline medullary stimulation

The present investigation determined whether the effects of electrical stimulation of depressor sites in midline medullary raphe nuclei were a result of inhibition of sympathoexcitatory medullospinal neurons in the rostral ventrolateral medulla of anesthetized cats. Electrical stimulation of the raphe inhibited inferior cardiac sympathetic activity. Microinjections of glutamate mimicked the effects of electrical stimulation. Electrical stimulation inhibited sympathoexcitatory neurons in the rostral ventrolateral medulla. The onset of the sympathoinhibition recorded from the inferior cardiac nerve (72 ms) was equal to the sum of the onset latency of the sympathoexcitatory response elicited from the rostral ventrolateral medulla (49 ms) plus the conduction time in the raphe to rostral ventrolateral sympathoinhibitory pathway (23 ms). Raphe stimulation excited a second set of neurons in the rostral ventrolateral medulla with an onset of 21 ms. Microiontophoretically applied bicuculline increased the discharge of sympathoexcitatory neurons and blocked the raphe-evoked inhibition. Iontophoretic glutamate excited sympathoexcitatory neurons but failed to antagonize raphe-elicited inhibition. These data suggest that neuronal elements in medullary raphe nuclei tonically inhibit sympathoexcitatory medullospinal neurons in the rostral ventrolateral medulla by activating closely adjacent gamma-aminobutyric acid (GABA) interneurons.

Slow cardioacceleration mediated by noncholinergic transmission in the stellate ganglion of the cat

In C1-spinal, pentobarbital-anaesthetized or anemically decerebrated cats, the preganglionic input to the acutely decentralized right stellate ganglion was stimulated with 10- to 30-s trains at 20–40 Hz. Electrical stimulation consistently produced an increase in heart rate in the presence of blocking doses of hexamethonium and atropine or after depletion of acetylcholine from the preganglionic axons by prolonged low frequency stimulation in the presence of hemicholinium. The increase in heart rate had a delayed slow onset, lasted several minutes, and was abolished by propranolol or by section of the inferior cardiac nerve. The magnitude and duration of the heart rate increase were related to intensity, frequency, and duration of preganglionic stimulation. The response to stimulation of a given white ramus was progressively attenuated, and eventually irreversibly lost, during prolonged continuous stimulation of that ramus, while the response to stimulation of a different unstimulated ramus was unchanged. We conclude that the slow cardioacceleration results from a slow and prolonged excitation of postganglionic neurons by a noncholinergic transmitter released by the preganglionic axons.

Postsynaptic adrenoceptor-mediated vasoconstriction in coronary and femoral vascular beds

This study examined the response to intra-arterial norepinephrine and sympathetic nerve stimulation on perfusion pressure of cannulated dog femoral and left circumflex coronary arteries perfused at constant flow rates. Sympathetic nerve stimulation was delivered through the decentralized inferior cardiac nerve and the lumbar sympathetic chain; beta-adrenergic blockade was maintained with propranolol. In the coronary artery, the vasoconstrictor response to norepinephrine was blunted by alpha 1-adrenergic blockade with prazosin but was abolished by alpha 2-adrenergic blockade with rauwolscine, indicating postsynaptic alpha 2-adrenoceptor-mediated vasoconstriction. In the femoral artery, prazosin decreased norepinephrine-induced vasoconstriction by 20-40%; the subsequent addition of rauwolscine completely abolished vasoconstriction, indicating that both alpha 1- and alpha 2-adrenoceptors contributed to vasoconstriction. Sympathetic nerve stimulation produced frequency-dependent increases of perfusion pressure in both coronary and femoral vascular beds. Prazosin caused approximately 50% reduction in the vasoconstrictor response of the coronary vascular bed and approximately 30% reduction in the femoral bed. The addition of rauwolscine completely blocked the response to sympathetic nerve stimulation in coronary and femoral vascular beds. These studies demonstrate that postsynaptic alpha 2-adrenoceptor-mediated mechanisms participate in vasoconstriction in response to both exogenous norepinephrine and sympathetic nerve stimulation in the canine coronary and femoral vascular beds.