Adrenal Nerve Research Articles

Effects of intra-cerebroventricular 2-dg infusion and subsequent hypothalamic lesion on adrenal nerve activity in the rat

Effects of intra-cerebroventricular 2-dg infusion and subsequent hypothalamic lesion on adrenal nerve activity in the rat

Differential effects of central angiotensin II and substance P on sympathetic nerve activity in conscious rats. Implications for cardiovascular adaptation to behavioral responses.

The centrally induced effects of angiotensin II and substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma noradrenaline and adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the angiotensin II-induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in diabetes insipidus rats and persisted in Long Evans rats after vascular vasopressin receptor blockade with d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-adrenoceptor blockade with prazosin or ganglion blockade with hexamethonium inhibited the central angiotensin II pressor responses only in combination with vasopressin receptor blockade. On the other hand, either sympatholytic drug, alone, abolished the pressor responses in the diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of angiotensin II are initiated by vasopressin release but become dependent on the sympathetic nervous system when vasopressin is absent or not effective. When rats were allowed to drink in response to angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central angiotensin II and substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of angiotensin II, or arousal within the central processing of pain, as in the case of substance P.

The effect of clonidine on adrenal sympathetic nerve responses to mechanical, noxious and innocuous stimulation of the skin in rats

The effect of clonidine on the reflex responses of the adrenal sympathetic nerve to mechanical stimulation of the lower chest skin was studied in anesthetized CNS intact and spinalized rats. Clonidine (3–120 μg/kg i.v.) administration resulted in a dose-related decrease in spontaneous adrenal efferent nerve activity in both CNS intact and spinalized rats. In CNS intact rats, noxious pinching caused a reflex increase in adrenal nerve activity while innocuous brushing caused a reflex decrease. In both cases, clonidine reduced the reflex response in a dose-dependent manner. In spinalized rats, both noxious and innocuous stimulation caused reflex increases in adrenal nerve activity, and clonidine produced a similar dose-dependent decrease in these responses as seen in CNS intact animals. The similar dose-response relationships for adrenal nerve tone or reflex response in CNS intact and spinalized animals suggest, although not conclusively, that at least some of clonidine's effects in CNS intact animals may be mediated at the spinal level.

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Ketanserin, a selective serotonergic (5-HT2) antagonist, also has affinity for alpha 1-adrenoceptors. It is not clear whether the hypotensive mechanism of ketanserin is due to its antagonistic action to 5-HT2 receptor or to its affinity for alpha 1 adrenoceptors. The hypotensive mechanism of ketanserin was studied in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anesthetized rats were used (alpha-chloralose + urethane, i.p.). Up to 3 ml of blood was drawn from each rat for analysis. Plasma norepinephrine (NE) was determined by radioenzymatic assay. Plasma serotonin (5-HT) was determined by HPLC-ECD. Adrenal nerve discharges were counted by a digital pulse counter. Ketanserin (0.5 mg/kg, 5.0 mg/kg, i.v.) produced a dose-dependent reduction of mean arterial pressure (MAP) in both SHRSP and WKY. MAP of SHRSP decreased significantly as compared with WKY. Both plasma NE and 5-HT showed a tendency to increase during ketanserin administration (5.0 mg/kg, i.v.). Ketanserin significantly antagonized the BP response induced by exogenously injected 5-HT (30 micrograms/kg) and NE (10 micrograms/kg). Adrenal nerve activity was reduced in parallel with the decrease in BP and HR. These findings suggest that ketanserin produced a decrease in BP via both peripheral and central action in rats.

Reflex discharges in the adrenal sympathetic efferent nerves evoked by electrical shocks of knee joint afferent nerves in anesthetized cats

Reflex discharges in the adrenal sympathetic efferent nerves evoked by electrical shocks of knee joint afferent nerves in anesthetized cats

The effect of clonidine on adrenal sympathetic nerve responses to mechanical, noxious and innocuous stimulation of the skin in rats

The effect of clonidine on adrenal sympathetic nerve responses to mechanical, noxious and innocuous stimulation of the skin in rats

Substance P-like immunoreactivity in adrenal chromaffin cells and intra-adrenal nerve fibers of rats

The present peroxidase-antiperoxidase immunohistochemical study demonstrated a relatively small number of cells with substance P(SP)-like immunoreactivity in the adrenal medulla of rats. These cells were found alone or in small groups, were polygonal in shape and lacked long cytoplasmic processes. At immunoelectron microscopy, the immunoreactive cells were characterized by abundant granular vesicles, and the immunoreactive material was confined to the round core of the vesicles. Thus, it is suggested that SP co-exists with catecholamines in a population of chromaffin cells of the rat adrenal medulla. In addition a few SP-immunoreactive nerve fibers with varicosities were found in the adrenal medulla of rats. They extended between small clusters of chromaffin cells and had their dot-like terminals around and within the cell clusters. The SP-immunoreactive nerve fibers were characterized by the presence of abundant small clear vesicles mixed with a few large granular vesicles; the immunoreactivity appeared in the latter, but was also perfused throughout the entire axoplasm. The nerve fibers formed synapses on nonimmunoreactive chromaffin cells. Judging from the presence of bundles of SP-immunoreactive nerve fibers penetrating the adrenal capsule and cortex as well as the absence of SP-immunoreactive ganglion cells in the medulla, the intramedullary SP-immunoreactive nerve fibers seem to be extrinsic in origin.

The occurrence of substance P-like immunoreactivity in adrenal chromaffin cells and intra-adrenal nerve fibers

The occurrence of substance P-like immunoreactivity in adrenal chromaffin cells and intra-adrenal nerve fibers

Reflex discharges in the adrenal sympathetic efferent nerves evoked by electrical shocks of knee joint afferent nerves in anesthetized cats

Reflex discharges in the adrenal sympathetic efferent nerves evoked by electrical shocks of knee joint afferent nerves in anesthetized cats

The occurrence of substance P-like immunoreactivity in adrenal chromaffin cells and intra-adrenal nerve fibers

The occurrence of substance P-like immunoreactivity in adrenal chromaffin cells and intra-adrenal nerve fibers

Reflex control of the autonomic nervous system activity from the glucose sensors in the liver in normal and midpontine-transected animals

Intraportal venous infusion of glucose resulted in a significant post-infusion decrease in the mean discharge rate in the adrenal nerve and the hepatic branch of the splanchnic nerve. Intraportal venous infusion of the same amount of glucose caused a significant increase in discharge rate of the pancreatic branch of the vagus nerve. After section of the hepatic branch of the vagus nerve, the same procedure induced no change in discharge rates in any of these nerves. Repetitive electrical stimulation of the central stump of the hepatic branch of the vagus nerve also caused reflex changes in efferent discharge rates in these three nerves, an increase in discharge rate in the hepatic branch of the splanchnic nerve and adrenal nerve, and a decrease in the pancreatic branch of the vagus nerve in the normal animals and also in midpontine-transected animals. The reflex network may consist of glucose-sensitive hepatic afferents, a reflex center in the hindbrain, and vagal pancreatic efferents, adrenal and splanchnic-hepatic efferents. This network contributes a neural regulatory mechanism to the control of blood glucose levels.

Reflex changes in sympatho-adrenal medullary functions in response to baroreceptor stimulation in anesthetized rats

Effects of increased and decreased blood pressure on adrenal sympathetic nerve activity and catecholamine secretion were examined in anesthetized Wistar rats. Efferent nerve impulses were counted and adrenal venous plasma was collected just before and 30 s after the onset of hypotensive stimulation induced by bleeding (average decrease in systolic blood pressure over the stimulation period was 38 mm Hg) or a hypertensive stimulation induced by phenylephrine administration (average increase in systolic blood pressure over the stimulation period was 41 mm Hg). While nerve activity and epinephrine and norepinephrine secretion were not significantly altered by the change in blood pressure in baroreceptor denervated animals, there were increases in these variables (131.1% of control levels for epinephrine, 117.5% for norepinephrine, and 127.1% for nerve activity) in response to bleeding and a marked decrease (to 63.0% of control levels for epinephrine, 53.9% for norepinephrine, and 54.0% for nerve activity) in response to phenylephrine administration with baroreceptors intact. These changes were significant both with respect to control blood pressure levels and with regard to the effect of stimulation in the baroreceptor-denervated animals. The reflex responses in adrenal nerve and catecholamine secretion were generally proportional in magnitude. The present results are discussed with regard to the effects of somatic stimulation on nerve activity and catecholamine secretion.

Effects of desipramine, trifluoperazine and other inhibitors of calmodulin on the secretion of catecholamines from the adrenal medulla and postganglionic sympathetic nerves of the salivary gland.

The effects of various drugs, known to be inhibitors of calmodulin, were tested on the secretion of catecholamines (CA) from the adrenal medulla and sympathetic nerves of the salivary gland of the rat. Secretion of CA from the perfused adrenal gland was evoked by injection of acetylcholine (ACh, 50 micrograms), excess K (700 micrograms), or transmural stimulation of splanchnic nerves (300 pulses at 10 Hz). Release of 3H-noradrenaline in the perfused salivary gland was evoked by transmural stimulation at 3 Hz for 30 s. CA secretion was reduced in a dose-dependent manner by 0.3 microM to 10 microM desipramine or imipramine. The effect of low doses (0.3 microM) was more pronounced on the secretion evoked by ACh and splanchnic nerve stimulation than that by excess K. The inhibition was independent of the frequency of nerve stimulation. Trifluoperazine (10-100 microM) and chlorpromazine (10-100 microM) reduced CA secretion evoked by all of the three procedures. The inhibitory effects of desipramine, trifluoperazine and chlorpromazine were completely reversed within 1 h after their washout. Secretion of CA obtained after reintroduction of Ca to the adrenal gland previously perfused with Ca-free medium was not blocked by desipramine or trifluoperazine. In fact, these agents markedly enhanced the secretory response. None of the drugs enhanced spontaneous secretion of CA from the adrenal gland during the nonstimulation period. Adrenal medullary cells accumulated significant amounts of Ca45 (0.88 pg/mg) after stimulation with ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

On the uptake and storage of 5-hydroxytryptamine, 5-hydroxytryptophan and catecholamines by adrenal chromaffin cells and nerve endings.

Light-microscopic autoradiographs of the adrenal medulla at various intervals after the intravenous injection of [3H] 5-HTP, [3H] 5-HT, [3H] noradrenaline and [3H] adrenaline have been studied. The distribution of silver grains following [3H] 5-HTP uptake was found to be uniform over each of the two main cell populations, adrenaline-storing (A) cells and noradrenaline-storing (NA) cells in the adrenal medulla, but A cells were twice as active as NA cells in incorporating the isotope, a situation very similar to that found after [3H] dopa uptake. 5-HT administration resulted in a pattern resembling the distribution of [3H] noradrenaline uptake, with A cells being 4 or 5 times more active than NA cells and a gradient of activity from the periphery of the medulla inwards. However, the time-course for the loss of radioactivity was not the same for both amines: levels of 5-HT activity were not significantly reduced after one week whereas the degree of [3H] noradrenaline labelling after one week was less than 10% of that at one hour. Thus 5-HT may be bound to sites in the adrenal medulla normally occupied by noradrenaline but it would appear that the release mechanism is different. There was no evidence of 5-HT uptake by adrenal nerve endings.

Widespread neural excitation initiated from cardiac spinal afferent nerves.

Reflex effects of cardiac sympathetic afferent nerve excitation on cardiac and renal components of sympathetic outflow have been well investigated, but the extent of these cardiac afferent influences on other sympathetic nerves or on respiratory or cortical neural systems is unknown. Therefore such influences were investigated electrophysiologically in anesthetized, vagotomized, baroreceptor-denervated cats. Stimulation of cardiac sympathetic spinal afferent neurons by the noxious substance bradykinin caused excitation of cardiac, renal, splenic, gastrohepatic, adrenal, and deep peroneal (muscle) vasoconstrictor sympathetic nerves, as well as excitation of phrenic nerves and concomitant desynchronization of the electroencephalogram. Possible supraspinal pathways mediating these responses were investigated. Sympathetic reflexes caused by cardiac afferent stimulation were unchanged after decerebration, thereby demonstrating that supramedullary mediation was not essential to the sympathetic responses. Potential contributions of the medulla to the observed sympathetic or other responses were demonstrated by recording from medullary neurons responsive to electrical and chemical stimulation of the afferent nerves. In summary, noxious stimulation of cardiac sympathetic afferent neurons leads to widespread neural excitation which may contribute to sensory, visceral, and somatic responses caused by cardiac pain or which occur during activated states such as exercise or emotional stress.

Central and peripheral effects of Clonidine on the adrenal medullary function in spontaneously hypertensive rats

Central and peripheral effects of Clonidine on the adrenal medullary function were investigated in spontaneously hypertensive rats (SHR, male 20-25 week old). For analysis of the adrenal medullary function, efferent adrenal nerve discharge rates and adrenal venous catecholamine secretion rates were determined. Effects of α-adrenoceptor blocking agents on the clonidine-induced adrenal suppressant effect were also investigated. The results obtained were as follows: (1) intravenous (i.c.v.) administration of Clonidine (3-100 μg/kg) decreased the adrenal nerve discharge rates and adrenal catecholamine secretion rates dose-dependently; (2) intra-cerebroventricular (i.e.v.) administration of Clonidine (1-10 μg) decreased the adrenal nerve activity dose-dependently; (3) i.v. administration of Clonidine (50 μg/kg) decreased the adrenal catecholamine secretion rates from the denervated adrenal medulla both during resting conditions and during electrical stimulation of the splanchnic nerve; (4) pretreatment with α2-adrenoceptor blocking agent, yohimbine (40 μg i.e.v.), antagonized the clonidine-induced decrease in adrenal nerve activity.

Response of adrenal efferent nerve activity to non-noxious mechanical stimulation of the skin in rats

The effects of brushing various segmental skin areas (neck, lower chest, abdomen and thigh) on adrenal sympathetic efferent nerve activity were examined in anesthetized rats. In the CNS intact rats, brushing of all areas produced a large reflex decrease in the efferent nerve activity, whereas, in the spinalized rats, brushing the lower chest or abdominal skin area produced an increased response while brushing the neck or thigh skin area produced no significant changes in the efferent nerve activity. It is suggested that the segmental excitatory organization of the adrenal nerve reflex caused by brushing within the spinal cord is modified into a non-segmental or generalized inhibitory organization by the supraspinal structure.

Sympathetic activity in spontaneously hypertensive rats after spinal transection.

To test the hypothesis that sympathetic hyperactivity and hyperexcitability in spontaneously hypertensive rats (SHR) is generated at spinal and/or ganglionic levels, we measured integrated renal nerve activity (before ganglionic blockade) and adrenal nerve activity (after ganglionic blockade) in 12- to 14-wk-old SHR and normotensive Wistar-Kyoto rats (WKY). Rats were anesthetized with alpha-chloralose, artificially respired, and paralyzed. Spinal cords were transected at C1 to eliminate normal supraspinal control of sympathetic activity. The effectiveness of descending sympathoexcitatory and sympathoinhibitory pathways was tested by measuring changes in nerve activity elicited by graded spinal stimulation. Spontaneous renal nerve activity was elevated in SHR, but stimulation of descending excitatory pathways caused similar responses in SHR and WKY. Spontaneous adrenal preganglionic nerve activity was similar in SHR and WKY, but excitatory stimulation elicited larger adrenal nerve responses in SHR. We conclude that spinal and/or ganglionic mechanisms may generate a component of the sympathetic hyperactivity exhibited by SHR. The larger adrenal preganglionic nerve responses to excitatory stimulation in SHR suggest that spinal systems may be partially responsible for adrenomedullary hyperexcitability in spontaneous hypertension.

Peripheral catecholamine release by alpha-latrotoxin in the rat.

Intraarterial injection of alpha-latrotoxin (alpha LTx), the major toxin of the black widow spider (Latrodectus mactans tredecimguttatus) venom, into carotid catheterized rats, induced prompt and marked rises in plasma adrenaline and noradrenaline concentrations, indicating that the toxin stimulates catecholamine release from both the adrenal medulla and sympathetic nerve terminals. Pretreatment with the ganglionic blocker chlorisondamine greatly reduced the plasma adrenaline response to alpha LTx but had almost no effect on the noradrenaline response, indicating that alpha LTx-stimulation of sympathetic nerve terminals is direct, whereas catecholamine release from the adrenal medulla is probably mediated by preganglionic release of acetylcholine. In vitro, alpha LTx induced a dose-dependent release of 3H-noradrenaline from rat irides preincubated with this radioactive amine and this effect was not changed by chlorisondamine plus atropine. By contrast, the toxin had no effect on 3H-noradrenaline release from suspensions of cultured rat chromaffin cells. Specific, high affinity binding of 125I-alpha LTx in iris and adrenal medulla homogenates was found to be exceedingly low, suggesting that it might be restricted to nerve terminals. No 125I-alpha LTx binding was seen nor could any effect of the toxin on 14C-5-hydroxytryptamine release be found in rat blood platelet preparations. alpha LTx binding and its amine releasing effect seem, therefore, to be specific for neurons and absent from other cells, even those, like adrenomedullary cells and blood platelets, which share with neurons their origin and/or other important characteristics.

Human catecholamine storage vesicle proteins.

Catecholamines in the adrenal medulla and sympathetic nerve are stored in vesicles, along with numerous proteins and peptides; both catecholamines and proteins are released by and are markers of exocytosis during sympathoadrenal neurosecretion. The proteins include the enzyme dopamine-beta-hydroxylase and the chromogranins, a group of molecules of largely undetermined function. We have isolated catecholamine storage vesicles (chromaffin granules) from bovine adrenal medulla and human pheochromocytoma. The numerous soluble proteins in the granules: (a) have a spectrum of sizes; (b) have a spectrum of charges; and (c) display considerable interspecies qualitative homology. Dopamine-beta-hydroxylase (DBH) was isolated from human and bovine vesicles by Concanaval in A affinity chromotography. DBH is a tetrameric glycoprotein consisting of 2 non-covalently joined dimeric subunits, each of which is 2 disulfide linked monomers; interspecies molecular weight differences were noted. Ongoing studies concern chromogranin A, the quantitatively major vesicle protein, in bovine and human vesicles.