Condition of Adrenergic Innervation Apparatus of the Thyroid Gland, Blood and Lymph Vessels, and Lymph Nodes during Correction of Hypothyrosis.

We used specific histochemical fluorescence-microscopic method of visualization of catecholamines to study adrenergic innervation of the thyroid gland tissue, blood vessels of the thyroid gland, cervical lymphatic vessel and lymph nodes in rats during correction of hypothyroidism with a bioactive formulation (Vozrozhdenie Plus balm with Potentilla alba L.). In experimental hypothyroidism, adrenergic innervation of the thyroid gland and the wall of the cervical lymph node, concentrated mainly along the arterial vessels and the cervical lymphatic vessel, retained its structural formations (plexuses and varicosities), but diffusion of catecholamines outside these formations was observed. Correction with the bioactive formulation restored of the contours of the nerve plexuses and varicosities and their brighter fluorescence in the thyroid gland and cervical lymphatic vessel and node. During correction of hypothyroidism with the bioactive formulation, reorganization of regional lymphatic vessels and nodes was more pronounced than reorganization of the thyroid gland.

The α2A -adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex.

KEY POINTS: The effects of noradrenaline on excitatory synaptic transmission to regular spiking (excitatory) cells as well as regular spiking non-pyramidal and fast spiking (both inhibitory) cells in cortical layer 4 were studied in thalamocortical slice preparations, focusing on vertical input from thalamus and layer 2/3 in the mouse barrel cortex. Excitatory synaptic responses were suppressed by noradrenaline. However, currents induced by iontophoretically applied glutamate were not suppressed. Further, paired pulse ratio and coefficient of variation analysis indicated the site of action was presynaptic. Pharmacological studies indicated that the suppression was mediated by the α2- adrenoceptor. Consistent with this, involvement of α2A -adrenoceptor activation in the synaptic suppression in excitatory and inhibitory cells was confirmed by the use of α2A -adrenoceptor knockout mice. ABSTRACT: The mammalian neocortex is widely innervated by noradrenergic (NA) fibres from the locus coeruleus. To determine the effects of NA on vertical synaptic inputs to layer 4 (L4) cells from the ventrobasal thalamus and layer 2/3 (L2/3), thalamocortical slices were prepared and whole-cell recordings were made from L4 cells. Excitatory synaptic responses were evoked by electrical stimulation of the thalamus or L2/3 immediately above. Recorded cells were identified as regular spiking, regular spiking non-pyramidal or fast spiking cells through their firing patterns in response to current injections. NA suppressed (∼50% of control) excitatory vertical inputs to all cell types in a dose-dependent manner. The presynaptic site of action of NA was suggested by three independent studies. First, responses caused by iontophoretically applied glutamate were not suppressed by NA. Second, the paired pulse ratio was increased during NA suppression. Finally, a coefficient of variation (CV) analysis was performed and the resultant diagonal alignment of the ratio of CV-2 plotted against the ratio of the amplitude of postsynaptic responses suggests a presynaptic mechanism for the suppression. Experiments with phenylephrine (an α1 -agonist), prazosin (an α1 -antagonist), yohimbine (an α2 -antagonist) and propranolol (a ß-antagonist) indicated that suppression was mediated by the α2 -adrenoceptor. To determine whether the α2A -adrenoceptor subtype was involved, α2A -adrenoceptor knockout mice were used. NA failed to suppress EPSCs in all cell types, suggesting an involvement of the α2A -adrenoceptor. Altogether, we concluded that NA suppresses vertical excitatory synaptic connections in L4 excitatory and inhibitory cells through the presynaptic α2A -adrenoceptor.

Nitric oxide-mediated central sympathetic excitation promotes CNS and pulmonary O2 toxicity.

In hyperbaric oxygen (HBO(2)) at or above 3 atmospheres absolute (ATA), autonomic pathways link central nervous system (CNS) oxygen toxicity to pulmonary damage, possibly through a paradoxical and poorly characterized relationship between central nitric oxide production and sympathetic outflow. To investigate this possibility, we assessed sympathetic discharges, catecholamine release, cardiopulmonary hemodynamics, and lung damage in rats exposed to oxygen at 5 or 6 ATA. Before HBO(2) exposure, either a selective inhibitor of neuronal nitric oxide synthase (NOS) or a nonselective NOS inhibitor was injected directly into the cerebral ventricles to minimize effects on the lung, heart, and peripheral circulation. Experiments were performed on both anesthetized and conscious rats to differentiate responses to HBO(2) from the effects of anesthesia. EEG spikes, markers of CNS toxicity in anesthetized animals, were approximately four times as likely to develop in control rats than in animals with central NOS inhibition. In inhibitor-treated animals, autonomic discharges, cardiovascular pressures, catecholamine release, and cerebral blood flow all remained below baseline throughout exposure to HBO(2). In control animals, however, initial declines in these parameters were followed by significant increases above their baselines. In awake animals, central NOS inhibition significantly decreased the incidence of clonic-tonic convulsions or delayed their onset, compared with controls. The novel findings of this study are that NO produced by nNOS in the periventricular regions of the brain plays a critical role in the events leading to both CNS toxicity in HBO(2) and to the associated sympathetic hyperactivation involved in pulmonary injury.

Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin.

Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at -1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm (Pre, -50.3 ± 3.3%; Post, -57.8 ± 2.2%), calf (Pre, -52.6 ± 3.7%; Post, -66.1 ± 4.3%), and palm (Pre, -46.2 ± 6.2%; Post, -60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.

Effect of the culture extract of Lentinus edodes mycelia on splenic sympathetic activity and cancer cell proliferation.

The spleen is an important organ for tumor immunity, and the splenic sympathetic nerve has a suppressive effect on splenic natural killer (NK) cytotoxicity. On the basis of this and reports that Lentinus edodes (Shiitake mushroom) has tumor-inhibitory effects, the authors hypothesized that an extract of a mycelial culture of L. edodes grown in a solid medium of sugar-cane bagasse and defatted rice bran-L.E.M-might affect the sympathetic splenic sympathetic nerve activity (Splenic-SNA) and thus inhibit tumor proliferation. Thus, the effect of L.E.M on Splenic-SNA and human cancer cell proliferation was examined. Splenic-SNA was found to be suppressed by an intraduodenal L.E.M injection in urethane-anesthetized rats, which significantly inhibited increases in the tumor volume of human colon and breast cancer cells implanted in athymic nude mice. These findings suggest that L.E.M has an inhibitory effect on tumor proliferation possibly via a reduction in NK cytotoxicity through the suppression of Splenic-SNA.

Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPARgamma activation. Administration of the PPARgamma agonist rosiglitazone (15 mg/kg.d) for 7 d to male Sprague Dawley rats increased food intake (10%), feed efficiency (31%), weight gain (45%), spontaneous motor activity (60%), and BAT and WAT mass and reduced whole-body oxygen consumption. Consistent with an anabolic setting, rosiglitazone markedly reduced sympathetic activity to BAT and WAT (>50%) and thyroid status as evidenced by reduced levels of plasma thyroid hormones (T(4) and T(3)) and mRNA levels of BAT and liver T(3)-generating enzymes iodothyronine type 2 (-40%) and type 1 (-32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of the thyroid hormone receptor (THR) isoforms alpha1 (-34%) and beta (-66%) in BAT and isoforms alpha1 (-20%) and alpha2 (-47%) in retroperitoneal WAT. These metabolic effects were associated with a reduction in mRNA levels of the pro-energy expenditure peptides CRH and CART in specific hypothalamic nuclei. A direct central action of rosiglitazone is, however, unlikely based on its low brain uptake and lack of metabolic effects of intracerebroventricular administration. In conclusion, a reduction in BAT sympathetic activity and thyroid status appears to, at least partly, explain the PPARgamma-induced reduction in energy expenditure and the fact that up-regulation of thermogenic gene expression does not translate into functional stimulation of whole-body thermogenesis in vivo.

Effect of electroacupuncture at Sibai on the gastric myoelectric activities of denervated rats.

AIM: To explore the mechanism of the exciting effects of electro-acupuncture (EA) at Sibai on the gastric myoelectric activities. METHODS: A total of 32 rats were randomly divided into four groups. Through intraperitoneal injection with atropine (the anti-cholinergic agent by blockade of muscarinic receptors), hexamethonium (automatic nerve ganglion-blocking agent) and reserpine (anti-adrenergic agent by depleting the adrenergic nerve terminal of its norepinephrine store), effects of EA at Sibai on the gastric myoelectric activities of the denervated rats were observed. RESULTS: After intraperitoneal injection of atropine and hexamethonium, the average amplitude and ratio of period to time in the phase of high activity of gastric myoelectric slow wave, and the average numbers of the peaks of gastric myoelectric fast wave were significantly decreased (P<0.01, P<0.05, P<0.01), while after intraperitoneal injection of reserpine, the aforementioned three parameters were increased (P<0.01, P<0.05, P<0.01). EA at Sibai point partially relieved the inhibitory effect of atropine and hexamethonium on the gastric myoelectric activities in the rats (P<0.05 or P>0.05). CONCLUSION: Cholinergic and adrenergic nervous systems and autonomic nerve ganglion participate in the peripheral passage of the controlling effects of EA at Foot Yangming Channel on gastrointestinal tract.

Risperidone potentiates the sympathetic and hyperthermic reactions induced by orexin A in the rat.

This experiment tested the effect of risperidone on the sympathetic and thermogenic effects induced by orexin A. The firing rates of sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colon temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 2 hours after the injection. The same variables were monitored in rats with an intraperitoneal administration of risperidone (50 mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is enhanced by the injection of risperidone. These findings suggest that risperidone elevates the responses due to orexin, probably through an involvement of serotoninergic and dopaminergic pathways, which are affected by risperidone. Furthermore, we suggested the name "hyperthermine A" as additional denomination of "orexin A" by considering the strong influence of this neuropeptide on body temperature.

Antinociceptive mechanisms associated with diluted bee venom acupuncture (apipuncture) in the rat formalin test: involvement of descending adrenergic and serotonergic pathways.

In a previous report, subcutaneous injection of diluted bee venom (dBV) into a specific acupuncture point (Zusanli, ST36), a procedure termed apipuncture, was shown to produce an antinociceptive effect in the rat formalin pain model. However, the central antinociceptive mechanisms responsible for this effect have not been established. Traditional acupuncture-induced antinociception is considered to be mediated by activation of the descending pain inhibitory system (DPIS) including initiation of its opioidergic, adrenergic and serotonergic components. The purpose of the present study was to investigate whether the antinociceptive effect of apipuncture is also mediated by the DPIS. Behavioral experiments verified that apipuncture significantly reduces licking behavior in the late phase of formalin test in rats. This antinociceptive effect of apipuncture was not modified by intrathecal pretreatment with naltrexone (a non-selective opioid receptor antagonist), prazosin (an alpha1 adrenoceptor antagonist) or propranolol (an beta adrenoceptor antagonist). In contrast, intrathecally injected idazoxan (an alpha2 adrenoceptor antagonist) or intrathecal methysergide (a serotonin receptor antagonist) significantly reversed apipuncture-induced antinociception. These results suggest that apipuncture-induced antinociception is produced by activation of alpha2 adrenergic and serotonergic components of the DPIS.

Haloperidol reduces the sympathetic and thermogenic activation induced by orexin A.

This experiment tested the effect of haloperidol on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before and 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same variables were monitored in rats with an intraperitoneal administration of haloperidol (1 mg/kg bw), a D(2) receptor antagonist. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures and heart rate. This increase is reduced by the haloperidol. These findings suggest that dopaminergic system is activated during the orexin A-induced hyperthermia.

Neuropeptides, amines and amino acids as mediators of the sympathetic effects of paraventricular nucleus activation in the rat.

The aim of the present study was to determine the influence on renal sympathetic nerve activity of the different chemically coded neuronal phenotypes that project from the paraventricular nucleus (PVN) to the spinal cord. Experiments were carried out on male Wistar rats anaesthetised with chloralose and urethane. Changes in renal sympathetic nerve activity were measured following activation of neurones in the PVN with D,L-homocysteic acid (100 nl, 200 mM), before and following intrathecal application of glutamate, vasopressin, oxytocin, dopamine and their receptor antagonists. Excitatory and inhibitory effects on renal sympathetic nerve activity were elicited by PVN stimulation. PVN excitatory effects were mimicked by intrathecal administration of glutamate and vasopressin and selectively antagonised by intrathecal administration of kynurenic acid and a V1a receptor antagonist, respectively. A low dose of dopamine increased renal sympathetic activity and this was selectively antagonised by haloperidol; however, the latter was without effect on PVN excitatory responses. A high dose of dopamine decreased renal sympathetic nerve activity and this was selectively blocked by a D1 dopamine receptor antagonist (SCH 23390), which also antagonised a minority of inhibitory responses obtained from the caudal extension of the PVN. Oxytocin also had two actions in 5 rats it inhibited and in 10 rats it increased renal sympathetic nerve activity, both actions being blocked selectively by oxytocin receptor antagonists. Neither of the PVN effects on renal sympathetic nerve activity appeared to be dependent on oxytocin pathways. Tests with intrathecal administration of bicuculline showed that PVN inhibition of renal sympathetic nerve activity was not dependent on spinal GABA(A) receptor activation. The results show that PVH-induced excitation of sympathetic activity to the kidney is mainly mediated by glutamate or vasopressin neurones whereas dopamine via Dl receptors may mediate some of the PVN inhibitory effects.

Alcohol rapidly lowers plasma testosterone levels in the rat: evidence that a neural brain-gonadal pathway may be important for decreased testicular responsiveness to gonadotropin.

Alcohol is reported to suppress testosterone (T) secretion in the adult male rat. Decreases in the circulating levels of luteinizing hormone (LH) and/or the activity of testicular steroidogenic enzymes have been proposed as putative mechanisms underlying this inhibitory effect. We have recently provided functional evidence for a neural pathway between the brain and the male gonads that plays an important role in the ability of brain proinflammatory cytokines to blunt testicular responsiveness to human chorionic gonadotropin (hCG). The present work was designed to test the hypothesis that a similar pathway might be implicated in the inhibitory influence of alcohol on T secretion. Alcohol, administered intraperitoneally or intragastrically, significantly prevented the T response to the gonadotropin. This effect was significant within 15 min of drug treatment. In the intragastric model (the only one used for this type of experiment), the effect of alcohol was not altered by prior blockade of LH release, which suggests that it is independent of changes in the activity of the pituitary gonadotrophs. The lowest effective dose of alcohol, delivered intraperitoneally, was 2.0 g/kg. The intracerebroventricular injection of the alpha- and beta-adrenergic receptor antagonists phentolamine and propranolol significantly reversed the inhibitory influence of alcohol when it was administered 15 min, but not 60 min, before hCG. Collectively, our results indicate that (1) alcohol induces a rapid and profound decrease in plasma T levels that is secondary to decreased testicular responsiveness to hCG; and (2) at least part of this acute inhibitory action of alcohol may depend on the activation of a neural, adrenergic-dependent pathway between the brain and the testes.

Effects of repeated cocaine injections on cochlear function.

The effects of repeated cocaine administration on cochlear function were evaluated by measuring amplitude-intensity and latency-intensity functions of the whole-nerve action potential of the auditory nerve. Whole-nerve action potential input/output functions obtained using tone-pips of 0.5, 1, 2, 4 and 8 kHz in a group of cocaine-treated subjects were compared with those obtained in saline-treated animals. All measurements were made 24 h after the last treatment. Amplitudes of whole-nerve action potentials were enhanced in the cocaine-treated animals compared to the control group. No statistically significant differences in latency-intensity functions were seen after cocaine treatment. The effect of chronic cocaine exposure also was examined on catecholamine innervation in the cochlea using immunohistochemical techniques. The density of adrenergic innervation was reduced in the cocaine-treated animals.

[The function of the peripheral adrenergic link under the action of neuroleptics in immobilization stress]. / Sostoianie perifericheskogo adrenergicheskogo zvena pri deistvii neiroleptikov v usloviiakh immobilizatsionnogo stressa.

The morphofunctional state of different links of the sympathoadrenal system under the action of neuroleptics haloperidol and sulpiride was studied on the model of immobilization stress in rats. The drugs were shown to possess the effect of the pharmacological correction of hormone content in the adrenals and the level of the neuromediator activity of the adrenergic nerves at different stages of immobilization stress. The data obtained indicate the anti-stress action of the studied neuroleptics. The effect of sulpiride is noted both in the early (the stage of anxiety) and late (the stage of exhaustion) periods of immobilization. The action of haloperidol is mainly limited to the stage of anxiety.

Selective effects of DSP-4 on locus coeruleus axons: are there pharmacologically different types of noradrenergic axons in the central nervous system?

There is considerable evidence from biochemical studies that the transmitter-depleting action of drugs and neurotoxins which act upon central noradrenergic (NA) axon terminals is not uniform in different brain regions. Among NA axons, those originating in the locus coeruleus (LC) have been proposed to be most susceptible to the action of NA neurotoxins such as N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). The studies described here were conducted to determine whether this differential susceptibility to DSP-4 reflects a pharmacological heterogeneity between different populations of NA axons. To determine whether DSP-4 acts selectively upon LC axons, we have characterized the effects of this drug on NA axons in different brain regions, by using noradrenaline and dopamine-beta-hydroxylase (D beta H) immunohistochemistry. Following systemic administration of DSP-4, there was an almost complete loss of noradrenaline and D beta H staining in brain regions innervated by LC axons. No effects of the drug treatment were detected in brain regions innervated primarily by non-coerulean NA axons. These results demonstrate that both the transmitter-depleting and the neurodegenerative action of DSP-4 are restricted to NA axons originating in the LC. To explore the basis for this selectivity, noradrenaline uptake studies were conducted using synaptosomes from brain regions in which NA axons differ in their response to DSP-4. The results reveal a significant difference in the affinity of DSP-4 for the noradrenaline uptake carrier in cortical and hypothalamic synaptosomes. This finding is compatible with the hypothesis that the noradrenaline uptake carrier is pharmacologically distinct in LC and non-coerulean NA axons. This heterogeneity in noradrenaline uptake raises the question whether other drugs may also have differential actions on LC and non-coerulean NA neurons.

[The adrenergic regulation of afferent cardiac reactions]. / Adrenergicheskaia reguliatsiia afferentnykh reaktsii serdtsa.

Adrenoreactive structures of the cat heart were studied with the EP technique in normal conditions and in acute damage of the myocardium. The intracardiac adrenergic systems were shown to be able to decrease the myocardium sensory thresholds and thus to aid to an increase in the heart nociceptive sensitivity as well as to take part in the development of intraorganic antinociceptive responses.

Prazosin treatment does not affect progestin receptor induction in microdissected regions of the rat hypothalamus.

Sex differences in estrogen-induced progestin receptors have been described in specific regions of the rat brain. To determine if alpha 1-neurotransmission plays a role in the expression of the sex differences in progestin receptor induction, the effects of the alpha 1-antagonist, prazosin, on progestin binding in microdissected regions of the rat brain was determined. Adrenalectomized/gonadectomized male or female rats were administered various doses of estradiol benzoate (EB) in combination with prazosin. With all treatment paradigms, and in both sexes, no significant effect of prazosin treatment on progestin receptor levels was observed. These results are consistent with the idea that sex differences in the estrogen-induction of progestin receptors in the rat hypothalamus are not due to sex differences in the alpha 1-adrenergic regulation of progestin receptor synthesis.

The effect of selective noradrenergic denervation on thyrotropin secretion in the rat.

The effect of DSP4 [N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine], a neurotoxin which selectively lesions noradrenergic projections from the locus coeruleus, on thyrotropin (TSH) secretion was investigated in the rat. DSP4 treatment (60 mg/kg injected i.p. 10 days prior to experimentation) significantly decreased the noradrenaline (NA) content of the hippocampus, frontal cortex and hypothalamus of the rat brain. DSP4 treatment did not affect the clonidine (250 micrograms/kg, i.p ) or TSH-releasing-hormone (TRH 5 micrograms/kg i.v.) induced stimulation or the isoproterenol induced inhibition of TSH secretion in the rat. These results suggest that the noradrenergic projection from the locus coeruleus to the hypothalamus does not play a significant role in the regulation of TSH secretion. Furthermore, the noradrenergic deficiency did not give rise to the development of the abnormal TSH response to TRH administration which is frequently observed in depression.

Epinephrine exacerbates arthritis by an action at presynaptic B2-adrenoceptors.

Sympathetic efferents contribute to the severity of joint injury in experimental arthritis in the rat, [Levine J. D. et al. (1986) J. Neurosci. 6, 3423-3429] and beta 2-adrenergic receptor antagonists suppress the disease [Levine J. D. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 4553-4556]. The present study was directed at determining the endogenous ligand for, and target of, the beta 2-receptor contribution to arthritis. We report that adrenal medullectomy significantly reduced joint injury in experimental arthritis, but that severe joint injury was re-established in adrenal medullectomized rats chronically treated with epinephrine or the beta 2-agonist, salbutamol. The ability of these two drugs to enhance joint injury in adrenal medullectomized rats was blocked by sympathectomy. These data suggest that adrenal medulla-derived epinephrine acts at beta 2-adrenoceptors on sympathetic efferent nerve terminals, to contribute to the severity of experimental arthritis.

Atrial natriuretic polypeptide attenuates central angiotensin II-induced catecholamine and ACTH secretion.

The interaction between angiotensin II (AII) and synthetic atrial natriuretic polypeptide (ANP) on the sympathetic nervous system and ACTH secretion was examined in unanesthetized, freely moving rats. Centrally administered AII (100 ng/2 microliters) caused hypertension with elevation of the plasma epinephrine level. Central administration of ANP (3 micrograms/3 microliters, 10 micrograms/3 microliters) attenuated central AII-induced pressor response and plasma epinephrine elevation. Furthermore, central AII stimulated ACTH secretion, and ANP reduced the ACTH secretion induced by AII. These results show that ANP attenuates the central AII-induced pressor response at least partially by suppressing sympathetic nervous activity, and ANP regulates ACTH secretion at the hypothalamic level.