Adrenal Medullary Secretion Research Articles

Evidence that exercise-induced heat storage is dependent on adrenomedullary secretion

To investigate the influence of medullary adrenal secretion on thermoregulation during exercise, Phy (Eserine, 5 × 10 − 3 M) was injected into the lateral cerebral ventricle of normal (INT) or bilaterally adrenodemedullated (ADM) untrained rats. Body temperature (Tb) and metabolic rate were measured in the rats while they were exercising on a treadmill (20 m min − 1 , 5% inclination) until fatigue or while they were at rest after drug injection. In resting rats, Phy increased oxygen consumption in both INT or ADM rats without any effect on core temperature. During the dynamic phase of exercise (first 20 min), ADM attenuated the exercise-induced increase in core temperature (0.86 ± 0.12 °C ADM Sal vs 1.48 ± 0.21 °C INT Sal), thus reducing heat storage (HS) levels. Icv injection of Phy in ADM rats significantly reduced the increase in Tb (0.012 ± 0.10 °C min − 1 Phy vs 0.042 ± 0.006 °C min − 1 Sal; p < 0.02) and HS (65.8 ± 56.1 cal Phy vs 207.7 ± 32.7 cal Sal; p < 0.04) compared to ADM Sal rats. In conclusion, the exercise-induced increase in heat storage was attenuated by adrenodemedullation in rats. Furthermore, the activation of heat loss mechanisms by the central cholinergic system during exercise occurs independently of adrenal medullary secretion suppression and can be improved by previous adrenodemedullation. Our data indicate the existence of a dual mechanism of heat loss control during the dynamic phase of exercise: one involving sympathoadrenal system activation that impairs heat loss and another that counteracts the increased sympathoadrenal activity through the hypothalamic cholinergic system to promote heat loss.

A physiological view of the central and peripheral mechanisms that regulate the release of catecholamines at the adrenal medulla

Here we review the tight neural control of the differential secretion into the circulation, of the adrenal medullary hormones adrenaline and noradrenaline. One or the other catecholamines are differentially released on various stress conditions. This is specifically controlled by central nervous system nuclei at the cortex, hypothalamus and spinal cord. Different firing patterns of splanchnic nerves and nicotinic or muscarinic receptors cause the selective release of noradrenaline or adrenaline, to adapt the body to the 'fight or flight' reaction, or during severe hypoglycaemia, haemorrhage, cold, acute myocardial infarction or other severe stressful conflicts. Endogenously acetylcholine (ACh) released at the splanchnic nerve-chromaffin cell synapse, acting on muscarinic and nicotinic receptors, causes membrane depolarization and action potentials (AP) in chromaffin cells. These changes vary with the animal species, the cell preparation (intact bisected adrenal, adrenal slices, or isolated fresh or cultured cells) or the recording technique (intracellular microelectrodes, patch-clamp, perforated-patch, cell-attached). Conflicting results leave many open questions concerning the actions of ACh on chromaffin cell excitability. The use of adrenal slices and field electrical stimulation will surely provide new insights into these mechanisms. Chromaffin cells have been thoroughly used as models to study the relationship between Ca2+ entry, cytosolic Ca2+ signals, exocytosis and endocytosis, using patch-clamp and amperometric techniques. Cells have been stimulated with single depolarizing pulses (DPs), DP trains and with simulated AP waveforms. These approaches have provided useful information but we have no data on APs generated by pulsatile secretory quanta of ACh, trying to mimic the intermittent and repetitive splanchnic nerve discharge of the neurotransmitter. We present some recent experiments using ultrashort ACh pulses (25 ms), that cause non-desensitizing repetitive APs with each ACh pulse, at low ACh concentrations (30 microM). Ultrashort pulses of a high ACh concentration (1000 microM) causes a single AP followed by a prolonged depolarization. It could be interesting trying to correlate these 'patterns of splanchnic nerve discharge' with Ca2+ signals and exocytosis. This, together with the use of adrenal slices and transmural electrical stimulation of splanchnic nerves will provide new physiologically sound data on the regulation of adrenal medullary secretion.

Mechanisms of Sympathetic Activation in Obesity-Related Hypertension

Obesity prevalence is soaring in industrialized countries and progressively increasing in the developing world. Altered patterns of nutrition and reduction in work-related energy expenditure have led to obesity becoming a truly global health issue. The central thermodynamic formulation for the origins of obesity, a mismatched energy balance equation, with an excess of dietary calorie intake over body energy expenditure, is a first step in the understanding of this phenomenon but leaves the diverse causal issues unexplored. Dietary calorie intake is modified by multiple social, economic, and cultural issues. Similarly, the reduction in energy expenditure in recent decades has complex origins, deriving from demographic and social change, which includes third-world transition from a labor-intensive agricultural economy to an industrial base, the introduction of household labor-saving devices, the popularity of transportation modes not reliant on physical effort, and from changed recreational habits, particularly in childhood (computer games instead of physical games). The prevalence of childhood obesity is escalating, having whimsically but not entirely unrealistically been attributed to “potato chips and computer chips.” Obesity and hypertension are intimately associated, and both very commonly coexist in individual patients with insulin resistance, hyperinsulinemia, and hyperlipidemia, this clustering of adverse health factors1 being designated the metabolic syndrome. The pathophysiological mechanisms by which obesity leads to hypertension remain uncertain. Understanding these processes might, perhaps, provide a more rational basis for drug treatment of obesity-related hypertension. Attempts at reduction in body weight, although pivotal in the treatment of obesity-related hypertension, more often than not fail, so that antihypertensive drug therapy is often needed. This review analyses the proposition that obesity is characterized by activation of the sympathetic nervous system and that obesity-related hypertension is, in fact, neurogenic, being initiated and sustained by neural mechanisms. At one time, this idea would have been held to fly in the …

Hindbrain catecholamine neurons control multiple glucoregulatory responses

Reduced brain glucose availability evokes an integrated constellation of responses that protect and restore the brain's glucose supply. These include increased food intake, adrenal medullary secretion, corticosterone secretion and suppression of estrous cycles. Our research has focused on mechanisms and neural circuitry underlying these systemic glucoregulatory responses. Using microinjection techniques, we found that localized glucoprivation of hindbrain but not hypothalamic sites, elicited key glucoregulatory responses, indicating that glucoreceptor cells controlling these responses are located in the hindbrain. Selective destruction of hindbrain catecholamine neurons using the retrogradely transported immunotoxin, anti-dopamine beta-hydroxylase conjugated to saporin (DSAP), revealed that spinally-projecting epinephrine (E) or norepinephrine (NE) neurons are required for the adrenal medullary response to glucoprivation, while E/NE neurons with hypothalamic projections are required for feeding, corticosterone and reproductive responses. We also found that E/NE neurons are required for both consummatory and appetitive phases of glucoprivic feeding, suggesting that multilevel collateral projections of these neurons coordinate various components of the behavioral response. Epinephrine or NE neurons co-expressing neuropeptide Y (NPY) may be the neuronal phenotype required for glucoprivic feeding: they increase NPY mRNA expression in response to glucoprivation and are nearly eliminated by DSAP injections that abolish glucoprivic feeding. In contrast, lesion of arcuate nucleus NPY neurons, using the toxin, NPY–saporin, does not impair glucoprivic feeding or hyperglycemic responses. Thus, hindbrain E/NE neurons orchestrate multiple concurrent glucoregulatory responses. Specific catecholamine phenotypes may mediate the individual components of the overall response. Glucoreceptive control of these neurons resides within the hindbrain.

Modulation of hypoglycemia‐induced increases in plasma epinephrine by estrogen in the female rat

Clinical studies have demonstrated that estrogen replacement therapy suppresses stress-induced increases in plasma catecholamines. The present study determined whether normal circulating levels of estrogen can modulate hypoglycemia-induced increases in plasma epinephrine (EPI). In anesthetized female rats, insulin-induced hypoglycemia (0.25 U/kg) increased plasma EPI concentration to a significantly greater extent in 14-day ovariectomized (OVEX) rats compared to that in sham-operated controls. In 17beta-estradiol (E2)-replaced OVEX rats, the hypoglycemia-induced rise in plasma EPI was reduced significantly when compared to that in vehicle-replaced OVEX rats. OVEX and E2 replacement had no effect on tyrosine hydroxylase or phenylethanolamine N-methyltransferase mRNA levels in the adrenal medulla. In isolated adrenal medullary chromaffin cells, agonist-induced increases in intracellular Ca2+ were unaffected by 48-hr exposure to 10 nM E2. In contrast, acute (3-min) exposure to micromolar concentrations of E2 dose-dependently and reversibly inhibited agonist-induced Ca2+ transients. In addition, in OVEX rats, a constant infusion of E2 significantly reduced the insulin-induced increase in plasma EPI concentration compared to that in vehicle-infused controls. These data demonstrate that physiologic levels of circulating E2 can modulate hypoglycemia-induced increases in plasma EPI. This effect seems independent of steroid influence on adrenal medullary secretion or biosynthesis. In contrast, acute exposure to high levels of E2 can also suppress hypoglycemia-induced increases in plasma epinephrine, due at least in part to inhibition of stimulus-secretion coupling.

Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation.

The toxin-antibody complex anti-d(beta)h-saporin (DSAP) selectively destroys d(beta)h-containing catecholamine neurons. To test the role of specific catecholamine neurons in glucoregulatory feeding and adrenal medullary secretion, we injected DSAP, unconjugated saporin (SAP), or saline bilaterally into the paraventricular nucleus of the hypothalamus (PVH) or spinal cord (T2-T4) and subsequently tested rats for 2-deoxy-D-glucose (2DG)-induced feeding and blood glucose responses. Injections of DSAP into the PVH abolished 2DG-induced feeding, but not hyperglycemia. 2DG-induced Fos expression was profoundly reduced or abolished in the PVH, but not in the adrenal medulla. The PVH DSAP injections caused a nearly complete loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the area of A1/C1 overlap and severe reduction of A2, C2, C3 (primarily the periventricular portion), and A6 cell groups. Spinal cord DSAP blocked 2DG-induced hyperglycemia but not feeding. 2DG-induced Fos-ir was abolished in the adrenal medulla but not in the PVH. Spinal cord DSAP caused a nearly complete loss of TH-ir in cell groups A5, A7, subcoeruleus, and retrofacial C1 and a partial destruction of C3 (primarily the ventral portion) and A6. Saline and SAP control injections did not cause deficits in 2DG-induced feeding, hyperglycemia, or Fos expression and did not damage catecholamine neurons. DSAP eliminated d(beta)h immunoreactivity but did not cause significant nonspecific damage at injection sites. The results demonstrate that hindbrain catecholamine neurons are essential components of the circuitry for glucoprivic control of feeding and adrenal medullary secretion and indicate that these responses are mediated by different subpopulations of catecholamine neurons.

Repeated 2-deoxy-D-glucose-induced glucoprivation attenuates Fos expression and glucoregulatory responses during subsequent glucoprivation.

A condition of reduced responsiveness to hypoglycemia, known as hypoglycemia-associated autonomic failure (HAAF), occurs in diabetic patients in the wake of a prior hypoglycemic episode. This condition suggests that hypoglycemia alters central glucose-sensing mechanisms. This experiment examined the effects of repeated 2-deoxy-D-glucose (2DG)-induced glucoprivation on subsequent 2DG-induced feeding and hyperglycemic responses in rats. Fos immunoreactivity (ir) in adrenal medulla and brain sites involved in these responses was also examined. Rats were injected daily for 10 days with 2DG (200 mg/kg) or saline (0.9%) or were handled. On day 11, rats were injected with 2DG (200 mg/kg). After injection, food intake was measured in one group. In another group, food was withheld, and multiple blood samples were collected for glucose determination. In a third group, food was withheld, and rats were killed after 2 h for evaluation of Fos-ir. Prior repeated glucoprivation reduced subsequent feeding and hyperglycemia responses to 2DG to baseline levels. Double-label immunohistochemistry showed that Fos-ir was reduced or abolished in catecholamine cell groups A1, A1/C1, C1, C3, and A6 and in the paraventricular nucleus of the hypothalamus and adrenal medulla. In other brain sites, 2DG-induced Fos-ir was diminished or unaffected by prior glucoprivation. Sites in which Fos-ir was abolished have been implicated previously in glucoprivic control of feeding and adrenal medullary secretion. Therefore, the present findings may identify crucial neuroanatomical sites that are altered by prior glucoprivation and that mediate some of the physiological deficits observed in HAAF.

Adrenal epinephrine secretion is not regulated by sympathoinhibitory neurons in the caudal ventrolateral medulla

By providing the principal inhibitory regulation of the discharge of sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), neurons in the caudal ventrolateral medulla (CVLM) play a major role in regulating the level of sympathetic nerve activity (SNA) to cardiovascular targets. To determine whether adrenal medullary secretion of epinephrine (EPI) is also regulated by sympathoinhibitory inputs from the CVLM to the RVLM, we compared levels of plasma EPI obtained after disinhibition of RVLM neurons with levels obtained after inhibition of CVLM neurons, both of which result in sustained elevations in arterial blood pressure (AP), SNA, and heart rate (HR). Plasma norepinephrine (NE) concentrations were significantly elevated following bilateral microinjection either of bicuculline (BIC) into the RVLM or of muscimol into the CVLM of urethane/chloralose-anesthetized, artificially-ventilated rats. In sharp contrast, although plasma EPI concentrations were significantly elevated following disinhibition of neurons in the RVLM, they were unchanged by inhibition of neurons in the CVLM. These results demonstrate that the discharge of sympathetic premotor neurons in the RVLM regulating adrenal secretion of EPI is modulated by a tonic, GABA-ergic inhibition that arises from a source that is different from the sympathoinhibitory neurons in the CVLM that project to RVLM sympathetic premotor neurons controlling vasoconstrictor and cardiac targets.

Reflex adrenal medullary secretion during coronary occlusion mediated by cardiac receptors with afferent vagal fibres in the rat.

The relative contribution of ventricular receptors and sinoaortic baroreceptors to the reflex release of adrenaline upon coronary occlusion was studied in anaesthetised rats submitted to a 30-min occlusion of the left coronary artery. Arterial adrenaline concentrations, heart rate and blood pressure were evaluated in control and sham-operated rats, and following sinoaortic denervation (SAD), bilateral vagotomy with and without SAD, ventricular application of lidocaine, neonatal treatment with capsaicin and cervical section of teh spinal cord. In all groups submitted to coronary ligation, blood pressure decreased sharply upon ligation and remained significantly reduced throughout occlusion while heart rate changes were not significant. In control rats, arterial adrenaline concentrations were significantly increased 15 and 30 minutes following coronary occlusion. The increase in adrenaline concentrations observed upon coronary ligation following SAD was not different from that of the control group. On the other hand, vagotomy with or without SAD, ventricular application of lidocaine, neonatal capsaicin treatment and spinal section all greatly reduced the increase in plasma adrenaline values. These results suggest that a large part of the reflex release of adrenaline upon coronary occlusion is mediated by ventricular receptors with unmyelinated vagal afferent fibres.

Effects of aging on epinephrine secretion and regional release of epinephrine from the human heart.

In contrast to the sympathetic nervous system, which is activated by aging in at least some sympathetic nervous outflows, epinephrine release from the adrenal medulla appears to be either normal or low in the elderly. Using isotope dilution methodology, we studied the effect of aging on the secretion of epinephrine in 19 men, aged 20-30 yr, and 15 men, aged 60-75 yr. Measurements were made both at rest and during the application of laboratory stressors, as diminished adrenal medullary responsiveness possibly contributes to the impairment of some cardiovascular and metabolic responses to stress described previously in the elderly. Epinephrine secretion at rest was lower in the older men (mean +/- SEM, 0.86 +/- 0.10 nmol/min) than in the younger men (1.45 +/- 0.17 nmol/min; P < 0.05). Due to 20% lower plasma epinephrine clearance in the older men (P < 0.01), the reduction in the plasma concentration of epinephrine (0.37 +/- 0.03 vs. 0.52 +/- 0.06 nmol/L; P = 0.06) was proportionally less than that in epinephrine secretion. In the younger men, epinephrine secretion doubled or tripled during mental stress, isometric exercise, and dynamic exercise. Epinephrine responses to the stressors were reduced in older men, being equivalent to only 44% (P < 0.05), 44% (P = 0.1), and 33% (P = 0.01) of the corresponding responses in the younger men. After uptake from plasma, in some circumstances epinephrine is released from sympathetic nerves as a cotransmitter, where it can augment the release of the major sympathetic transmitter, norepinephrine. We also measured regional extraadrenal release of epinephrine from the heart to test whether the previously described increased release of norepinephrine from the cardiac sympathetic nerves with aging might result from facilitator effects of epinephrine released as a cotransmitter. At rest, epinephrine was released from the heart (9.4 +/- 2.6 pmol/min) in older men only (P < 0.01) despite the fact that adrenal medullary secretion of epinephrine was reduced. Failure of epinephrine and norepinephrine spillover from the heart to increase in parallel in the elderly during the sympathetic excitation accompanying exercise suggested that epinephrine lay outside the sympathetic nerves, perhaps arising from extraneuronal synthesis in the heart. We have not yet tested whether extraneuronal, in contrast to neuronal, epinephrine release in the heart could contribute to the observed higher rates of norepinephrine release in the elderly.

Effects of nifedipine and Bay K 8644 on stimulation-induced adrenal catecholamine secretion in the dog

The effects of nifedipine and BAY K 8644 on the adrenal medullary secretion in response to direct splanchnic nerve stimulation were studied in anesthetized dogs. Supramaximal stimulation (12 V) was given on the left splanchnic nerve at a frequency of 2 Hz with three different pulse durations (0.2, 2, and 20 ms) for a total period of 1.5 min. Each stimulation was given for 30 s without interruption between each stimulation. Plasma concentrations of epinephrine and norepinephrine were measured in adrenal venous and aortic blood. In the vehicle control group, epinephrine and norepinephrine concentrations in adrenal venous blood proportionally increased with the lengthening of the pulse duration without significant changes in catecholamine concentrations in aortic blood. In dogs receiving nifedipine (100 micrograms/kg iv), the net increase in adrenal venous epinephrine concentration during stimulation with 20-ms pulse duration was attenuated by approximately 50% (P < 0.05). In dogs treated with BAY K 8644 (30 micrograms.kg-1.min-1 iv), both adrenal venous epinephrine and norepinephrine secretions evoked by stimulation with 20-ms pulse duration were significantly enhanced by approximately 50%. The present results suggest that the secretion of adrenal catecholamines under in vivo conditions is controlled through mechanism(s) involving dihydropyridine sensitive L-type Ca2+ channels presumably localized on the surface of adrenal medullary chromaffin cells.

Adrenal medullary secretion with splanchnic stimulation in spinal cats

This project was undertaken to determine whether previously observed adrenal medullary hyperactivity that developed following high spinal cord transection in the cat could be explained by increased sensitivity of the synapse between the splanchnic nerve and chromaffin cell. The splanchnic nerve was stimulated in acute (2–3 h; n = 7) or chronic (61–64 days; n = 7), spinally transected (T3) cats that were decerebrate and unanesthetized. Mean arterial blood pressure and adrenolumbar venous blood flow were significantly greater in the chronic animals. Stimulation (30 V; 1 ms pulses) was applied at 3 Hz and 30 Hz to deliver the same number of pulses within 3 min. Adrenal medullary secretion (ng/min) of epinephrine (EPI), norepinephrine (NE), dopamine, neuropeptide Y (NPY), [Met]enkephalin (ENK), and encrypted [Met]enkephalin was determined at baseline and in relation to both patterns of stimulation. With near threshold (3 Hz) stimulation, the following differences were observed between groups: (1) secretion of EPI, NPY, and ENK was significantly greater in the chronic than in the acute animals; and (2) preferential secretion of NE was elicited in the acute animals. These observations suggest that there may be some facilitation of the splanchnic nerve—chromaffin cell synapse that occurs over time following high thoracic spinal cord transection. However, it is likely that central, spinal mechanisms also contribute to adrenal medullary hyperactivity.

Norepinephrine release induced by potassium in the aging heart: Lack of influence of adrenal demedullation

There is considerable evidence suggesting that control by the adrenergic nervous system of cardiac function is decreased with increasing age. To determine if catecholamines originating in the adrenal medulla influence adrenergic transmission at the cardiac neuroeffector junction as a function of age, the heart was isolated from rats who were adrenal demedullated 2 weeks prior to isolation. In 24-month-old animals which were adrenal demedulated, hydrocortisone replacement was employed for one week; the animals were killed one week later. Norepinephrine (NE) release was induced by potassium (K+). Hearts were isolated from male Fischer 344 rats of two ages (6-and 24-month) and were perfused with Krebs-Ringer solution. K+ was employed at a 90 μmoles dose and the amount of NE in the effluent measured by HPLC/EC methodology. The amount of NE released by K+ was diminished in heart preparations from older animals. Adrenal demedullation did not influence the capacity of K+ to release NE from the heart. This suggests that the age-related decrease in NE release in the heart is not due to changes in adrenal medullary secretion.

Characterization of cardiovascular and behavioral responses to alerting stimuli in rats.

Freely moving rats exhibit complex motor and cardiovascular responses to tactile stimulation (12.5 psi air puff, 100-ms duration). In naive Wistar-Kyoto rats, the behavioral response is characterized by a short-latency (25 +/- 1 ms) jumping event, the magnitude of which habituates to repeated stimuli. In a paradigm of consecutive tactile stimuli, each delivered at 30-s intervals, the arterial pressure (AP) response is consistent in profile (36.4 +/- 1.7 mmHg, initial stimulus) and habituates rapidly (15.4 +/- 2.2 mmHg, at 20th stimulus). Rates of habituation of the jumping behavior and AP increase are similar and significantly correlated (P less than 0.01), suggesting partial common mediation. Heart rate changes are bimodal and highly dependent on stimulus number. Initial stimuli elicit bradycardia (-42 +/- 7 beats/min), habituating to extinction by stimulus 10. A temporally delayed tachycardia becomes evident by trial 5 (19 +/- 5 beats/min) and persists unchanged throughout the remainder of the 30-stimulus session. Delayed tachycardia may represent activation of secondary autonomic mechanisms. The nature of cardiovascular responses elicited by the tactile stimulus suggests a somatomotor reflex mediated through the ventrolateral medulla. Adrenal enucleation exaggerated the magnitude of transient bradycardia and abolished extinction of bradycardia with repeated stimuli. Adrenal medullary secretion has only minor importance in direct mediation of the response, but this study suggests that adrenal function plays an important role in tonically setting the level of cardiac responsiveness to parasympathetic vs. sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential catecholamine responses to dietary intake: Effects of macronutrients on dopamine and epinephrine excretion in the rat

Sympathetic nervous system (SNS) function responds to changes in diet in animals and humans; whether alterations in peripheral dopaminergic activity or in adrenal medullary secretion also occur with dietary manipulation is unclear. The present studies in rats demonstrate that casein supplementation of a lab chow diet raised urinary excretion of dopamine (DA) and epinephrine (E); both sucrose and lard feeding suppressed urinary DA, though only lard appeared to exert any effect on E excretion (reduction). Addition of tyrosine to the chow diet in an amount equivalent to the tyrosine content of casein increased DA output comparably to that seen in casein-fed rats, but did not reproduce the effects of casein on E excretion. Oral administration of carbidopa, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylation in kidney reduced the DA response to casein, but chemical sympathectomy, which lowered urinary norephnephrine (NE), and adrenal denervation, which diminished E excretion, did not. Thus, the patterns of response of the peripheral dopaminergic system in kidney and of the adrenal medulla to short-term nutrient and tyrosine ingestion are distinct from those observed for the SNS and for each other, suggesting that all three peripheral catecholamine systems may be governed by separate regulatory mechanisms.

Adrenergic receptors of adrenal medullary vasculature.

The present study evaluates possible effects of adrenal catecholamines, released by splanchnic nerve stimulation, on adrenal medullary blood flow (MQ) and adrenal catecholamine secretion (CS). Twelve pentobarbital-anesthetized mongrel dogs were subjected to three identical splanchnic nerve stimulations (5 V, 20 Hz, for 3 min) at 30-min intervals, and MQ (radiolabeled microsphere technique) and CS (high-performance liquid chromatography) were measured before and during each nerve stimulation. Animals were assigned to one of three groups and administered either saline, pindolol (1 and 4 mg/kg), or prazosin (1 and 4 mg/kg) before the second and third nerve stimulation, respectively. In the saline control group, each nerve stimulation resulted in similar increases in MQ and CS. Pindolol attenuated nerve stimulation-induced increases in MQ and CS by 50%, but had no effect on medullary catecholamine concentration. Prazosin augmented nerve stimulation-induced MQ, CS, and medullary catecholamine concentration by 35%. These data suggest that adrenal adrenergic receptors modulate elicited CS and mediate changes in adrenal medullary vascular tone.

Regional adrenal blood flow during hypoxia in anesthetized, ventilated dogs

The effect of hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) on adrenal medullary (MQ) and cortical (CQ) blood flow (radiolabeled microsphere technique) was studied in pentobarbital sodium-anesthetized, mechanically ventilated dogs. Animals were exposed to 60 min of hypoxia (arterial O2 content 8 vol%) induced by adding either nitrogen (HH, n = 6) or carbon monoxide (COH, n = 6) to the inspired gas. Whole adrenal Q and CQ increased by 70 and 50%, respectively, with HH but were unchanged during COH. MQ, however, increased threefold during both HH and COH. HH and COH both increased arterial levels of epinephrine, corticosteroids, and adrenocorticotropic hormone (ACTH). To determine whether the increase in CQ during HH was because of HH-induced increases in mean arterial blood pressure (MAP, approximately 20 mmHg), an additional group of animals (n = 6) was exposed to HH but had MAP maintained at control levels using a pressurized-bottle system. MAP control did not alter the CQ response to HH. We conclude that MQ appears to be associated with medullary secretory activity during hypoxia and that HH and COH stimulate adrenal medullary secretion equally. In contrast, CQ increases only with HH, despite similar increases in ACTH and corticosteroid levels during HH and COH, suggesting that an alternative mechanism is responsible for increased cortical blood flow during HH.

Effect of subthalamic stimulation on adrenal epinephrine and norepinephrine secretion in the rat

Adrenal medullary secretion in response to subthalamic stimulation was studied in pentobarbital-anesthetized rats. Stimulation of the lateral part of the zona incerta resulted in a significant increase in epinephrine secretion. Stimulation of some other areas of the subthalamus produced a significant decrease in epinephrine as well as in norepinephrine secretion. These results suggest that in the zona incerta excitatory and inhibitory central nervous system mechanisms exist for the control of the adrenal medullary secretion.

Role of sympathoadrenal and renin-angiotensin system in hemodynamic state after coronary artery bypass grafting.

To evaluate the role of the sympathoadrenal and renin-angiotensin systems in postoperative hemodynamic state, plasma concentrations of catecholamines, renin activity, angiotensin, and aldosterone as well as hemodynamics were studied following coronary artery bypass grafting in 55 patients. The patients were divided into four groups: 1) uneventful, 2) hypertension (HT), 3) hypotension for which cateeholamines were administered (CAT), and 4) perioperative myocardial infarction (POMI). The mean cardiac index in the HT group was higher than that in the Uneventful group and some patients in the HT group showed high adrenaline level. A group of patients who had a hypertensive episode and then sustained low cardiac output state (HT-to-LOS group) showed marked elevation of systemic vascular resistance index and noradrenaline level. These findings suggest that the hypertensive episodes in the HT-to-LOS group may be primarily caused by the activation of the sympathetic nerve system and that those of some patients in the HT group may be caused by marked adrenal medullary secretion. Five patients (56%) in the HT group showed plasma renin activity of more than 5.0 ng/ml/hr. and three patients (33%) showed angiotensin II of more than 100 pglml. Thus, postoperative hypertension seems to be multifactorial in nature. The POMI group represented significant elevation of plasma adrenaline concentration and significantly low sensitivity to catecholamines of the ventricle accompanied with impaired left ventricular performance. Although the mean aldosterone level in the CAT group was significantly higher than that in the Uneventful group, only a few patients of the CAT group demonstrated marked elevation of aldosterone concentration which might cause a vicious circle to develop. Clinical significance of modest increase of aldosterone concentration in other patients in the CAT group is questionable.

The effect of chemical sympathectomy on catecholamine release at birth.

The precise source of circulating catecholamine (CA) at birth and their role in circulatory adaptation is unclear. In order to determine the contribution of increased postganglionic sympathetic nerve activity to the CA surge at birth, we induced complete sympathectomy in near term fetal lambs prior to delivery by giving 6-hydroxydopamine. Chronically catheterized fetal sheep received either 6-hydroxydopamine (n = 5) or control infusion (n = 6). Chemical sympathectomy was verified by tyramine infusion. Lambs were delivered at 142 +/- 1 days of gestation and serial plasma CA, heart rate, blood pressure, cardiac output, blood gases, blood glucose, and free fatty acids, were measured before and for 4 h after delivery. Myocardial beta-adrenergic receptors and tissue CA concentration were determined following sacrifice. Baseline circulating norepinephrine (NE) values were lower in sympathectomized animals (183 +/- 45 versus 373 +/- 125 pg/ml, p less than 0.05) and epinephrine values were slightly higher (118 +/- 89 versus 48 +/- 1 pg/ml, NS). There was only a 2-fold increase in NE after cord cutting in sympathectomized animals while control animals had a 4-fold increase (peak NE values 354 +/- 121 versus 1305 +/- 363 pg/ml respectively, p less than 0.001). Epinephrine increased significantly in both groups and there were no significant differences between sympathectomized and control animals. Heart rate and blood pressure rose abruptly in both groups after cord cutting and there were no significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)