Postganglionic Renal Nerve Research Articles

Hypercapnia induces long-term changes in postganglionic renal nerve activity in the piglet

In developing swine, time and frequency domain analyses were used to compare changes in discharge features of efferent phrenic and postganglionic renal nerve activities evoked by prolonged (1 h) exposure to severe hypercapnia (10% CO 2, balance O 2), before and after combined carotid sinus and aortic depressor nerve (CSN–AOD) sectioning. With intact CSN–AOD innervation, respiration-related activity in renal nerve discharge was rare (3 of 11 animals) during baseline periods with intact innervation, but was observed in most cases (10 of 11 animals) during baseline following denervation. Renal nerve respiration-related activity was recruited by hypercapnic stimulation in animals with intact CSN–AOD innervation, and was augmented in denervated animals with ongoing respiratory activity. Phrenic nerve discharge was markedly augmented during hypercapnia, whether CSN–AOD innervation was intact or not, and it did not exhibit a post-hypercapnic depression. Autopower spectra of renal nerve activity revealed the presence of two coexisting rhythms, 2–6 and 7–13 Hz, which were present whether CSN–AOD innervation was intact or not. The hypercapnic-induced increases of activity in the 2–6 and 7–13 Hz bands were not comparable, with the latter region exhibiting a much more robust response to hypercapnia, especially following CSN–AOD denervation. Thus, prolonged exposure to hypercapnia evoked changes in renal nerve discharge that involved increased coupling to neuronal ensembles shaping central inspiratory activity and those generating central sympathetic outflows, especially to networks generating 7–13 Hz rhythm. Such changes may permit more efficient modulation of innervated structures during exposure to stressors.

OPIOID RECEPTOR MODULATION OF NEURAL TRANSMISSION IN THE RABBIT COELIAC GANGLION AND GANGLIONIC OPIOID RECEPTOR ACTIVATION BY BUNITROLOL

1. We examined the preganglionic splanchnic nerve activity and postganglionic renal nerve activity before and after a local injection of naloxone (20 micrograms/kg) into the coeliac ganglion of anaesthetized rabbits. This was done during graded hypertension, induced by the administration of phenylephrine (0.5-10 micrograms/kg, i.v.) and with selective intraganglionic injection of methionine-enkephalin (ME) and bunitrolol, which is a beta-blocker. 2. During hypertension both pre- and postganglionic discharge decreased, but only postganglionic discharge was inhibited by naloxone treatment into the ganglion. 3. Local injection of ME (0.1-10 micrograms/kg) into the coeliac ganglion decreased postganglionic activity by 9.0 +/- 1.0 to 41.2 +/- 4.7% from control, and this decrease was inhibited by naloxone. 4. Administration of bunitrolol (1-300 micrograms/kg) decreased postganglionic discharge by 3.9 +/- 1.4 to 39.7 +/- 2.4% of the control and this decrease was also inhibited by naloxone. 5. These results suggest that opioid receptors in the coeliac ganglion play an inhibitory role in neural ganglionic transmission and that this inhibitory action reduces postganglionic sympathetic discharge.

Lack of interaction between a hypertonic NaCl stimulus and the brain renin-angiotensin system.

Sodium and the renin-angiotensin system (RAS) participate in the regulation of cardiovascular function, in part via activation of central nervous system (CNS) mechanisms. Because intraventricular (IVT) administration of either hypertonic sodium chloride (NaCl) or angiotensin II (ANG II) elicits similar effects (i.e., natriuresis, hypertension, increased drinking, and enhanced vasopressin release) a common and final pathway may be involved. With this in mind, we measured the effect of an IVT injection (third or lateral ventricle) of 0.6 M NaCl on postganglionic renal nerve activity (RNA) and blood pressure in morphine-pentobarbital-anesthetized dogs before and after blockade of the brain RAS with either captopril or [Sar1,Ile8]ANG II. Both vagus and carotid sinus nerves were cut to avoid impingement of the baroreceptor reflex on the measured variables. IVT injection of 0.6 M NaCl produced a prominent hypertensive response and tachycardia associated with a 59 +/- 9% increase in RNA. These changes were statistically significant (P less than 0.001), correlated with each other, and were abolished by administration of hexamethonium chloride (10 mg/kg iv). Blockade of central ANG II receptors with [Sar1,Ile8]ANG II was without effect. However, in dogs given IVT SQ 14,225, there was a slight increase in baseline RNA before injection of 0.6 M NaCl; in addition, both the pressor and heart rate responses to the stimulus of hypertonic NaCl were further augmented. These results demonstrate that central administration of hypertonic NaCl in baroreceptor-denervated dogs produces marked activation of sympathetic nerve activity via mechanisms other than activation of the brain RAS.

Reduction in blood pressure, sympathetic nerve discharge and centrally evoked pressor responses by methysergide in anesthetized cats

Methysergide (1 and 3 mg/kg i.v.) caused dose-dependent reductions in blood pressure and heart rate of anesthetized cats. In addition, sympathetic nerve discharges of the postganglionic renal nerve was also markedly reduced by the same doses of drug. Pressor responses to electrical stimulation of the diencephalon were inhibited by 3 mg/kg but not 1 mg/kg of methysergide. These results suggest that methysergide acts to decrease blood pressure by a centrally mediated reduction in sympathetic nervous outflow and, at higher doses, can additionally prevent pressor changes caused by electrical activation of suprabulbar central structures. These results are in agreement with previous reports that methysergide has little or no peripheral effects on the cardiovascular system.

Baroreceptor mechanisms controlling sympathetic nervous rhythms of central origin.

A study was made in the anesthetized cat of the slow wave of sympathetic nervous discharge (SND) locked in a 1:1 relation to the cardiac cycle (3 cycle/s periodicity). SND was recorded from the preganglionic splanchnic and postganglionic renal nerves. The data contradict the generally accepted view that the slow wave occurs as the direct result of a waxing and waning of baroreceptor nervous discharge. Although baroreceptor denervation unlocked the phase relations between SND and the cardiac cycle, the slow wave persisted and its duration was not changed. Furthermore, the slow wave was aborted by stimuli delivered to the baroreceptor nerves or paramedian reticular nucleus during a time span which accounted for less than 1 percent of the cardiac cycle. It is concluded that the 3 cycle/s periodicity of SND is representative of a vasomotor rhythm of central origin which is entrained to the cardiac cycle by the baroreceptor reflexes. The sympathoinhibitory effect leading to the entrainment of the slow wave is mediated in the brainstem. ta spinal component of baroreceptor-induced sympathoinhibition also was demonstrated.

Further similarities between the action of clonidine and a central activation of the depressor baroreceptor reflex.

The relationship between the central action of the hypotensive drug clonidine and the depressor baroreceptor reflex was studied in cats anaesthetized with urethane. Activation of the depressor baroreceptor reflex was achieved by bilateral electrical stimulation of the sinus nerves. The magnitude of the activation of the reflex was estimated from the resultant decrease in spontaneous sympathetic activity recorded from the preganglionic splanchnic and a postganglionic renal nerve and from the subsequent fall in blood pressure. The effect of bilateral sinus nerve stimulation was frequency-dependent over the range of 2 to 32 shocks/sec and allowed the construction of frequency-response curves. Clonidine in low doses (1 and 3 μg/kg i.v.), which caused no or only a slight depression of spontaneous sympathetic nerve activity and of the blood pressure, increased the response to bilateral sinus nerve stimulation with a resultant shift of the respective frequency-response curves to lower rates of stimulation. Clonidine also augmented the bradycardia produced by an activation of the depressor baroreceptor reflex. These results indicate a facilitation of the depressor baroreceptor reflex by clonidine.

Excitatory and inhibitory components of somato-sympathetic reflex

In cats anesthetized with chloralose it was confirmed that electrical stimulation of somatic nerves evoked a reflex volley (late response) followed by a transient inhibition of the spontaneous discharge (silent period) in the sympathetic postganglionic renal nerve. The thresholds for both the late response and silent period were in the same range, from 1.2 to 1.5 times the threshold for the fiber excitation in the superficial radial nerve, and from 2.5 to 3.0 times in the hamstring and sciatic nerves. The independent occurrence of the silent period from the late response was demonstrated in recovery tests. Furthermore, lesions in the dorsal surface area of the medulla oblongata selectively abolished or greatly depressed the late response, whereas lesions in the ventral medullary reticular formation selectively abolished or greatly depressed the silent period.

Buffer reflexes, tolerance to ganglioplegics and their relationship to enhanced pressor responsiveness.

Tetraethylammonium, hexamethonium, chlorisondamine or mecamylamine suppressed the dog's carotid occlusion reflex well before appearance of maximum augmentation of responses to pressor drugs. The reflex usually returned to near control values despite continued administration of ganglioplegics, while augmented responsiveness persisted or became more marked. An antipseudocholinesterase or prostigmine restored the suppressed reflex without loss of augmented responsiveness. Electroneurographic measurements of efferent spontaneous activity in postganglionic renal nerves revealed synaptic pathways resistant to blockade: a small amount of activity persisted during tolerance to ganglioplegics and showed reflex changes. Similar measurements of spontaneous and evoked potentials in the inferior cardiac nerve showed no synaptic activity during tolerance. Augmentation of response to pressor drugs by ganglioplegics does not depend wholly upon loss of compensatory reflexes; peripheral sensitization is probably another mechanism concerned. Maintenance of arterial pressure and persistence of cardiovascular reflexes during tolerance to ganglioplegics appear to depend upon transmission of a relatively few impulses over pathways resistant to blockade and upon peripheral sensitization to the presumably smaller amounts of norepinephrine released from nerve endings.