Corelease of neuropeptide Y like immunoreactivity with catecholamines from the adrenal gland during splanchnic nerve stimulation in anesthetized dogs

The release of neuropeptide Y like immunoreactivity (NPY-li) from the adrenal gland was studied in relation to the secretion of catecholamines (CA: NE, norepinephrine; E, epinephrine) during the left splanchnic nerve stimulation in thiopental-chloralose anesthetized dogs (n = 16). Plasma concentrations of NE, E, and NPY-li were determined in the left adrenal venous and aortic blood. Adrenal outputs of NPY-li, NE, and E were 2.4 +/- 0.4, 1.4 +/- 0.2, and 7.3 +/- 1.7 ng/min, under basal conditions, respectively. These values increased significantly (p less than 0.05; n = 8) in response to a continuous stepwise stimulation at frequencies of 1, 3, and 10 Hz given at 3-min intervals during 9 min, reaching a maximum output of 4.6 +/- 0.9 (NPY-li), 240.2 +/- 50.2 (NE), and 1412.5 +/- 309.7 ng/min (E) at a frequency of 10 Hz. Burst electrical stimulation at 40 Hz for 1 s at 10-s intervals for a period of 10 min produced similar increases (p less than 0.05) in the release of NPY-li (4.8 +/- 1.0 ng/min, n = 8), NE (283.5 +/- 144.3 ng/min, n = 8), and E (1133.5 +/- 430.6 ng/min, n = 8). Adrenal NPY-li output was significantly correlated with adrenal NE output (r = 0.606; n = 24; p less than 0.05) and adrenal E output (r = 0.640; n = 24; p less than 0.05) in dogs receiving the burst stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of catecholamine release by endogenous adenosine in the rat adrenal medulla

Adenosine was shown to inhibit norepinephrine (NE) release from sympathetic nerve endings. The purpose of this study was to examine whether endogenous adenosine restrains NE and epinephrine release from the adrenal medulla. The effects of an adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl) xanthine (DPSPX), on epinephrine and NE release induced by intravenous administration of insulin in conscious rats were examined. Plasma catecholamines were measured by HPLC with an electrochemical detector. DPSPX significantly increased plasma catecholamine in both control rats and rats treated with insulin. The effect of DPSPX on plasma catecholamine was significantly greater in rats treated with insulin. Additional experiments were performed in adrenalectomized rats to investigate the contribution of the adrenal medulla to the effect of DPSPX on plasma catecholamine. The effect of DPSPX and insulin on epinephrine in adrenalectomized rats was significantly reduced compared with that of the controls. Finally, we tested whether endogenous adenosine restrains catecholamine secretion partially through inhibiting the renin-angiotensin system. The effect of DPSPX on plasma catecholamine in rats pretreated with captopril (an angiotensin-converting enzyme inhibitor) was reduced. These results demonstrate that under basal physiological conditions, endogenous adenosine tonically inhibits catecholamine secretion from the adrenal medulla, and this effect is augmented when the sympathetic system is stimulated. The effect of endogenous adenosine on catecholamine secretion from the adrenal medulla is achieved partially through the inhibitory effect of adenosine on the renin-angiotensin system.     

Adrenal vein catecholamines and neuropeptides during splanchnic nerve stimulation in cats

Splanchnic nerve stimulation in bursts at low (5 Hz) and high (50 Hz) frequency (30 V, 1 msec; train duration 1 sec; train rate 0.5/second) was employed in 10 cats under halothane anesthesia, during 10-minute periods, while blood samples were concurrently collected from the adrenal vein and femoral artery for the measurement of norepinephrine (NE), epinephrine (EPI), dopamine (DA), Met-enkephalin (ME), neuropeptide Y (NPY), peptide YY (PYY) and neurotensin (NT). In Group I (n = 5), splanchnic nerve stimulation was initially applied at 5 Hz followed after 20 min by a 50 Hz stimulus, while in Group II (n = 5) the stimulation sequence was reversed. Adrenal vein and femoral artery plasma levels of catecholamines and neuropeptides were not significantly affected by the stimulation sequence, while a significant decrease in blood pressure response was observed in Group II during the 5 Hz stimulation as compared to Group I, indicating desensitization. Splanchnic nerve stimulation at 5 Hz caused a preferential increase in adrenal vein NE (9-fold) versus EPI (7-fold) levels as compared to baseline, while 50 Hz stimulation led to further comparable increases in NE (5-fold) and EPI (6-fold) levels. Significant increases in adrenal vein DA and neuropeptide levels were only observed during 50 Hz stimulation, with DA showing a 5-fold, ME a 2.6-fold and NPY a 3-fold increase as compared to 5 Hz stimulation, and NT a 3.6-fold increase as compared to baseline. Present findings indicate different dynamics in the movement of catecholamines and neuropeptides from the adrenal.     

Comparison of the effects of neuropeptide Y and adrenergic transmitters on LH release and food intake in male rats

In view of the recent demonstrations that Neuropeptide Y (NPY) and adrenergic transmitters coexist in neurons of the rat brain, we have compared the effects of intraventricular (Ivt) injections of NPY and catecholamines on LH release and food intake in intact male rats. Of the three catecholamines, dopamine (DA), norepinephrine (NE) and epinephrine (E), only E (5.3 micrograms or 15.9 micrograms/rat) significantly stimulated LH release, although NE and E (5.3 micrograms/rat) were equally effective in eliciting food intake in satiated rats. Ivt administration of 10 micrograms NPY significantly stimulated LH release, whereas either lower (0.5 or 2 micrograms/rat) or higher (25 micrograms/rat) doses were ineffective. In contrast, NPY at doses of 0.5 - 10 micrograms/rat increased cumulative food intake in a dose-related fashion. These findings present preliminary evidence of the physiological correlates of the neuronal coexistence of adrenergic transmitters and NPY in the brain and raise the possibility that NPY may normally act either independently, in concert with or via adrenergic systems to evoke LH release and feeding responses in the rat.     

Influence of age and splanchnic nerve on the action of melatonin in the adrenomedullary catecholamine content and blood glucose level in the avian group

Summary A single intraperitoneal (IP) melatonin injection (0.5 mg/100 g body wt.) caused an increase in norepinephrine (NE) fluorescence and elevation of NE content in newly-hatched pigeons (Columba livia), but a reduction of NE fluorescence and depletion of NE content in the adrenal medulla of newly-hatched crows (Corvus splendens) after 0.5 h of treatment. In contrast, in adults melatonin caused increase in NE fluorescence and elevation of NE content only in the parakeet (Psittacula krameri).Half an hour of IP melatonin treatment (0.5 mg/100 g body wt.) induced release of epinephrine (E) from the adrenal medulla of newly-hatched pigeon and parakeet. In contrast, in the adults melatonin caused more than a two-fold increase in E in the pigeon, and a significant increase in the crow.Single IP melatonin injection (0.5 mg/100 g body wt.) caused hypoglycemia in the newly-hatched parakeet and adult pigeon, and hyperglycemia in newly-hatched pigeon after 0.5 h of treatment. Melatonin failed to regulate glucose homoeostasis in newly-hatched and adult crow.Splanchnic denervation of the left adrenal gland was performed in the adult pigeon. The right adrenal served as the innervated gland. Melatonin-induced modulation of catecholamines following a single IP injection (0.5 mg/100 g body wt.) revealed significant increases in NE fluorescence and NE content at 4 and 12 h after treatment in the denervated gland only, which gradually approached normal levels 9 days after treatment. In contrast, E content showed more than a two-fold increase over the control value in both the innervated and denervated glands 0.5 and 24 h after treatment. At 9 days after treatment, E content showed significant depletion in the innervated gland.The results of this study indicate that melatonin modulates catechol hormone content in avian adrenal medulla, and also regulates glucose homoeostasis (except in the crow). The splanchnic nerve plays a vital role in the synthesis of NE but has no effect on E.     

Epinephrine and dopamine colocalization with norepinephrine in various peripheral tissues: guanethidine effects

Chemical sympathectomy with guanethidine (Gnt) selectively destroys the postganglionic noradrenergic neurons, whereas dopaminergic fibers and nonneural catecholamine-secreting cells are spared. As a result, the relative proportions of norepinephrine (NE), epinephrine (E), and dopamine (DA) in tissues can be differentially affected. This study was done to show the possible differences in the relative amount of catecholamines in some organs and tissues that might indicate the nature of the secretory cells from which they originate. The contents of NE, E, and DA were assessed in rats neonatally treated with Gnt. Gnt-treated rats showed significantly lower levels of NE (P < 0.01) in all tissues except the adrenal gland and paraganglia. Epinephrine was present in all tissues with mean levels below 25 ng/g, with the exception of the adrenal gland (700 microg/gland) and paraganglia (100 ng/g). Only the heart showed lower values in Gnt-treated rats. Mean DA levels were also very high in paraganglia (530 ng/g). In the Gnt-treated rats, DA levels fell practically to zero except in the duodenum, mesentery, and adrenal, whereas there were high levels in the paraganglia, which were significantly different from controls. The results suggest that the three catecholamines are contained mainly in noradrenergic sympathetic fibers of muscle, white adipose tissue, heart, liver, pancreas, and spleen. The duodenum and mesentery may have dopaminergic fibers or E- and DA-containing nonneural cells. Hepatic-vagus paraganglia contain all the catecholamines in relatively high amounts in nonneural cells, and Gnt treatment raises DA levels without affecting the other amines.     

Methionine-enkephalin facilitates the cardiovascular response to epinephrine in the conscious dog

Methionine-enkephalin (ME) is present in high concentrations in the adrenal medulla; it is co-stored with catecholamines in chromaffin vesicles, and released together with catecholamines during adrenal stimulation. We have examined the interactions of intravenously administered bolus doses of ME and epinephrine (EPI) in the conscious dog. EPI, 1.0 μg/kg, increased mean arterial pressure (MAP) from 104±6 to 130±11 mm Hg, while reflexly reducing heart rate(HR) from 103±13 to 83±13 beats/min (bpm). ME, 5.0 μg/kg, increased MAP from 106±7 to 122±7 mm Hg and increased HR from 111±12 to 139±14 bpm. EPI and ME administered together increased MAP in apparently additive fashion from 106±6 to 153±12 mm Hg, and also increased HR from 102±10 to 114±17 bpm. ME, 1.0 μg/kg, exerted a similar effect. Thus, in these concentrations, ME exerts a co-operative influence upon the EPI cardiovascular response in the conscious, neurologically intact dog, probably by inhibiting baroreceptor reflexes. These findings suggest a possible role for ENK as an excitatory stress hormone.     

Effect of functional adrenalectomy on glucagon secretion and circulating catecholamines during insulin hypoglycemia in the dog

The present study was carried out to determine whether an increase in the pancreatic immunoreactive glucagon (IRG) secretion during the acute phase of insulin-induced hypoglycemia depends on circulating catecholamines of adrenal origin. Hypoglycemia was induced by a bolus insulin injection (0.15 IU/kg, i.v.) in dogs anesthetized with sodium pentobarbital (35 mg/kg, i.v.). Plasma aortic epinephrine (E) and norepinephrine (NE) concentrations increased significantly 30 min after the injection of insulin. At this time point, a functional adrenalectomy (diversion of bilateral adrenal venous blood from the systemic circulation) was performed for 5 min. The increased aortic E and NE concentrations significantly decreased reaching, within 5 min, a level below the corresponding preinjection control value. The basal output of pancreatic IRG (6.58 +/- 1.12 ng/min, n = 6) significantly increased (24.93 +/- 2.77 ng/min, p less than 0.05, n = 6) 30 min after insulin injection. During the functional adrenalectomy, the increased pancreatic IRG output diminished rapidly, within 5 min, to approximately 50% (11.73 +/- 3.19 ng/min, p less than 0.05, n = 6) of the value observed 30 min after insulin administration. In the other group of dogs receiving sham adrenalectomy, the increased aortic E and NE concentrations and pancreatic IRG output following insulin injection remained elevated above the levels observed immediately before the sham adrenalectomy. The net decrease in IRG output during the adrenalectomy was significant (p less than 0.05) compared with the corresponding net IRG output observed in the sham group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of epinephrine and norepinephrine on glucose release from chinook salmon (Oncorhynchus tshawytscha) liver incubated in vitro

The effects of two catecholamines, epinephrine (EP) and norepinephrine (NE), on carbohydrate metabolism were studied by incubating chinook salmon liver in vitro. Basal release of glucose over the course of a 5-h incubation was 7.93 +/- 1.70 mumol/g dry weight. Both EP and NE (2 X 10(-7) M) stimulated glucose release rapidly during the first hour. After 5 h, EP and NE significantly increased glucose release over basal levels to 43.55 +/- 9.01 and 32.75 +/- 6.17 mumol/g dry weight, respectively. Epinephrine- and NE-stimulated glucose release was dose dependent, with a minimum effective dose of 10(-9) M. ED50 for both agents was approximately 2 X 10(-7) M; maximal stimulation occurred at 10(-5) M. No difference in potency between the two catecholamines was found. The effects of adrenergic agonists and antagonists were also studied. Alpha-agonists, methoxamine and phenylephrine, had no effect on glucose release. Isoproterenol, a beta-agonist, stimulated glucose release in a manner similar to EP. The beta-antagonist, propranolol, inhibited both catecholamine- and isoproterenol-stimulated glucose release. Alpha-antagonists (phentolamine, prazosin, and yohimbine) had no effect on either catecholamine- or isoproterenol-stimulated glucose release. Epinephrine and NE stimulate glycogen phosphorylase activity; propranolol inhibits catecholamine-stimulated phosphorylase activity. These results indicate that catecholamines stimulate glucose mobilization in salmon liver by promoting glycogenolysis mediated through beta-adrenergic receptors.     

Direct evidence that an increase in aortic norepinephrine level in response to insulin-induced hypoglycemia is due to increased adrenal norepinephrine output

This study reports on the major source of circulating norepinephrine that is known to increase, progressively, during sustained hypoglycemia induced by intravenous insulin administration. Plasma concentrations of epinephrine, norepinephrine, and dopamine were simultaneously determined for adrenal venous and aortic blood in dogs anesthetized with sodium pentobarbital. The model used allowed us to perform a functional adrenalectomy (ADRX), while continuously monitoring the adrenal medullary secretory function. Under basal conditions, the net output (micrograms/min) of adrenal epinephrine, norepinephrine, and dopamine were 0.169 +/- 0.074, 0.067 +/- 0.023, and 0.011 +/- 0.003, respectively. Plasma concentrations (ng/mL) of aortic epinephrine, norepinephrine, and dopamine were 0.132 +/- 0.047, 0.268 +/- 0.034, and 0.034 +/- 0.009. Following insulin injection (0.15 IU/kg, i.v.), the net output (micrograms/min) of adrenal epinephrine, norepinephrine, and dopamine increased gradually (p less than 0.05), reaching the values of 0.918 +/- 0.200, 0.365 +/- 0.058, and 0.034 +/- 0.007 30 min after insulin administration. Similarly, aortic epinephrine, norepinephrine, and dopamine concentrations (ng/mL) increased significantly (p less than 0.05) to 0.702 +/- 0.144, 0.526 +/- 0.093, and 0.066 +/- 0.024. The aortic glucose concentration (mg/dL) was diminished from 81.8 +/- 4.1 to 36.9 +/- 3.4 (p less than 0.01). After taking the blood sample at 30 min following insulin administration, ADRX was immediately performed. Five minutes after the onset of ADRX, the net output (micrograms/min) of adrenal epinephrine, norepinephrine, and dopamine increased further to 1.707 +/- 0.374 (p less than 0.05), 0.668 +/- 0.139 (p less than 0.05), and 0.052 +/- 0.017.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of hypoinsulinemia modifies catecholamine effects in fetal sheep

Increased epinephrine (Epi) and norepinephrine (NE) production plays an important role in fetal adaptation to reduced oxygen and/or nutrient availability, inhibiting insulin secretion and slowing growth to support more essential processes. To assess the importance of hypoinsulinemia for the efficacy of catecholamines, normoinsulinemia was restored by intravenous insulin infusion (0.18 mU. kg(-1). min(-1)) during prolonged infusion of either Epi (0.25-0. 35 microgram. kg(-1). min(-1) for 12 days, n = 7) or NE (0.5-0.7 microgram. kg(-1). min(-1) for 7 days, n = 6) into normoxemic fetuses in twin-pregnant ewes, from 125-127 days of gestation. Insulin infusion for 8 days during Epi infusion or for 4 days during NE infusion decreased arterial blood pressure, O(2) content, and plasma glucose, but increased heart rate significantly (all P <0.05), despite continuation of Epi or NE infusion. Cessation of insulin infusion reversed these changes. Estimated growth of fetuses infused with insulin during Epi or NE infusion (55 +/- 13.9 and 83 +/- 15.2 g/day) did not differ significantly from that of untreated controls (72 +/- 15.4 g/day, n = 6). Growth of selected muscles and hindlimb bones was not altered either. Restoration of normoinsulinemia evidently counteracts the redistribution of metabolic activity and decreased anabolism brought about by Epi or NE in the fetus. Inhibition of insulin secretion by Epi and NE, therefore, appears essential for the efficacy of catecholamine action in the fetus.     

Influence of photoperiods on glycemic and adrenal catecholaminergic responses to melatonin administrations in adult male roseringed parakeets, Psittacula krameri Neumann

Effects of daily (one hour prior to onset of darkness) injection of melatonin (25 micrograms/100 g body wt. for 30 days) on concentrations of blood glucose and adrenal catecholamines were studied in adult male roseringed parakeets, P. krameri under both natural (NP; about 12L:12D) and artificial long (LP; 16L:8D; lights were available in between 0600 and 2200 hrs) or short (SP; 8L:16D; lights were available between 0600 and 1400 hrs) photoperiodic conditions. The results indicate that neither LP, nor SP as such exerts any significant effect on blood glucose titre of control (vehicle of hormone administered) birds. Treatment with melatonin, however, induced hyperglycemia in both NP and LP bird groups, but hypoglycemia in SP birds. Unlike glycemic levels, amount of epinephrine (E) and norepinephrine (NE) in adrenals of control birds exhibited significant changes under altered photoperiods. A decrease in E and an increase in NE were noted in adrenals of both LP and SP birds. Exogenous melatonin in NP birds also caused a decrease in E and concomittant rise in NE levels. On the other hand, treatment of melatonin in both LP and SP bird groups resulted in an increase in the quantity of both E and NE compared to respective values in adrenals of melatonin injected NP birds. However, relative to the amount of E and NE in adrenals of placebo treated LP and SP birds, significant effect of melatonin treatment was observed only in SP birds. The results suggest that influences of exogenous melatonin on the levels of both blood glucose and adrenal catecholamines are largely modulated by short rather than long photoperiods.     

The protective effect of vagus nerve stimulation on catecholamine-halothane-induced ventricular fibrillation in dogs

Parasympathetic neural activity modulates some ventricular arrhythmias in man. Therefore, a canine model of arrhythmias produced by the interaction of halothane and catecholamines was used to study the effects of vagal stimulation on the induction of ventricular fibrillation. The dose of catecholamine required to induce ventricular fibrillation was determined during a constant heart rate. Vagal stimulation reversibly raised the norepinephrine dose that produced ventricular fibrillation from 16.4 +/- 2.4 to 30.0 +/- 3.8 micrograms (p less than 0.001, n = 10), and the epinephrine dose from 15.5 +/- 2.0 to 22.5 +/- 2.6 micrograms (p less than 0.001, n = 5). Following atropine, vagal stimulation failed to raise the threshold dose of norepinephrine (16.8 +/- 2.4 vs. 18.3 +/- 3.3 micrograms, nonsignificant, n = 6) or epinephrine (15.5 +/- 2.0 vs. 16.0 +/- 2.3 micrograms, nonsignificant, n = 5). Ligation of the cervical vagus nerves did not affect the epinephrine threshold dose (16.3 +/- 3.3 vs. 17.5 +/- 2.7 micrograms, nonsignificant, n = 5). Following elevation of basal vagal tone by morphine premedication, the norepinephrine threshold of 53.0 +/- 9.2 micrograms declined by a nonsignificant amount to 46.5 +/- 11.5 micrograms after vagotomy (nonsignificant, n = 5). Thus resting vagal tone does not prevent catecholamine-halothane-induced ventricular fibrillation, whereas increasing vagal tone by electrical stimulation substantially protects against this arrhythmia. The protection is mediated through a muscarinic cholinergic receptor.     

Activation of Melatonin Receptor Sites Retarded the Depletion of Norepinephrine Following Inhibition of Synthesis in the C3H/HeN Mouse Hypothalamus

The aim of the present study was to determine the effect of activation of melatonin receptor sites on the activity of noradrenergic neurons in the C3H/HeN mouse brain. Changes in noradrenergic activity were assessed by measuring norepinephrine (NE) levels in the hypothalamus, frontal cortex, and hippocampus following inhibition of NE synthesis with alpha-methyl-p-tyrosine (alpha-MpT) (300 mg/kg, i.p., 2 h). 6-Chloromelatonin (1-30 mg/kg, i.p.) significantly retarded the alpha-MpT-induced decrease in NE levels in the hypothalamus, but not in hippocampus and frontal cortex. This effect was observed at 30 min and 60 min after 6-chloromelatonin administration and was dose dependent. At noon, when the levels of endogenous melatonin are low, the melatonin receptor antagonist luzindole (30 mg/kg, i.p., 30 min) did not affect the depletion of NE by alpha-MpT; however, it (1-30 mg/kg) completely antagonized the 6-chloromelatonin-induced reduction of NE depletion elicited by alpha-MpT in hypothalamus. These results suggest that activation of melatonin receptor sites in brain of C3H/HeN mouse retarded the depletion of NE elicited by alpha-MpT. At midnight, when the levels of melatonin are high, luzindole (30 mg/kg) significantly accelerated the depletion of NE by alpha-MpT in hypothalamus, but not in frontal cortex or hippocampus, suggesting activation of melatonin receptor sites by endogenous melatonin. We conclude that activation of melatonin receptor sites in C3H/HeN mouse brain by endogenous melatonin inhibits the activity of noradrenergic neurons innervating the hypothalamus.     

Angiotensin II mediates catecholamine and neuropeptide Y secretion in human adrenal chromaffin cells through the AT1 receptor

The aim of the present work was to study the effect of angiotensin II (Ang II) on catecholamines and neuropeptide Y (NPY) release in primary cultures of human adrenal chromaffin cells. Ang II stimulates norepinephrine (NE), epinephrine (EP) and NPY release from perifused chromaffin cells by 3-, 2- and 12-fold, respectively. The NPY release is more sustained than that of catecholamines. We found that the receptor-AT(2) agonist, T(2)-(Ang II 4-8)(2) has no effect on NE, EP and NPY release from chromaffin cells. We further showed that Ang II increases intracellular Ca(2+) concentration ([Ca(2+)](i)). The selective AT(1)-receptor antagonist Candesartan blocked [Ca(2+)](i) increase by Ang II, while T(2)-(Ang II 4-8)(2) was ineffective. These findings demonstrate that AT(1) stimulation induces catecholamine secretion from human adrenal chromaffin cells probably by raising cytosolic calcium.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.     

Angiotensin in the brain suppresses epinephrine-induced cardiac arrhythmias through CNS opioid mechanisms.

To test the hypothesis that angiotensin II (Ang II) in the central nervous system modulates catecholamine-induced cardiac arrhythmias and to determine whether endogenous opioids are operative in this action, arrhythmias were produced in male Wistar rats, by continuous infusion of epinephrine at incremental doses until the development of fatal arrhythmias that were usually ventricular fibrillation. Rats were instrumented with catheters in the lateral cerebral ventricle, femoral vein and femoral artery. Ang II, 0.5 microgram, in the lateral cerebral ventricle (ICV) markedly and significantly (p less than 0.05) increased the epinephrine dose, at the occurrence of ventricular premature beats compared to the control group 228 +/- 11 (SEM) vs 116 +/- 7 micrograms epinephrine/kg and at the onset of fatal arrhythmias 225 +/- 13 vs 185 +/- 9 micrograms epinephrine/kg. Ang II, 0.5 microgram i.v., did not affect arrhythmia threshold. The angiotensin converting enzyme inhibitor captopril, 1 mg/kg, decreased arrhythmia threshold as ventricular arrhythmias were first noted at 106 +/- 4 and fatal arrhythmias occurred at 118 +/- 4 micrograms epinephrine/kg. The Ang II receptor antagonist saralasin 150 micrograms/kg ICV, blunted and 300 micrograms/kg ICV reversed the effect of Ang II. The mu opioids antagonist naloxone and the kappa opioid antagonist MR 2266, 50 micrograms/kg ICV, prevented the effect of Ang II on fatal arrhythmias. The action Ang II on arrhythmias could not be explained by the effects of Ang II on blood pressure or heart rate. These data indicate a role for Ang II within the CNS to modulate cardiac arrhythmias and that this is mediated in part, by endogenous opioids.     

The effect of etorphine on nicotine- and muscarine-induced catecholamine secretion from perfused rat adrenal glands

The effect of etorphine on nicotine and muscarine-mediated catecholamine (CA) release from isolated perfused rat adrenal glands was investigated. Nicotine increased CA secretion at the low concentration of 0.5 micrograms while higher concentrations of muscarine (5 micrograms) were required. Moreover, muscarine released primarily epinephrine (EP) from rat adrenal glands while nicotine released norepinephrine (NE) and Ep. Etorphine inhibited NE and EP release evoked by nicotine to the same extent, whereas, muscarine-mediated release of NE and EP was not affected. Mecamylamine and verapamil inhibited nicotine but not muscarine-induced CA secretion. Our results suggest that etorphine preferentially interacts with nicotinic receptors on rat adrenal chromaffin cell membranes.     

Catecholamine concentrations in plasma and organs of the fetal guinea pig during normoxemia, hypoxemia, and asphyxia

To examine the responses of the sympatho-adrenal system to reduced oxygen supply we studied plasma and tissue concentrations of catecholamines during normoxemia, hypoxemia, and asphyxia in 22 fetal guinea pigs near term. Fetal blood was obtained by cardiopuncture in utero under ketamine/xylazine-anesthesia. Catecholamines were determined in plasma and tissue of 15 organs and 14 brain parts by HPLC-ECD. During normoxemia (SO2 54 +/- 4 (SE) %, pH 7.36 +/- 0.02, n = 5) plasma catecholamine levels were low (norepinephrine 447 +/- 53, epinephrine 42 +/- 12, dopamine 44 +/- 6 pg/ml). During hypoxemia (SO2 27 +/- 3%, pH 7.32 +/- 0.01, n = 6) and asphyxia (SO2 24 +/- 2%, pH 7.23 +/- 0.02, n = 11) tissue catecholamine concentrations changed with changing blood gases and with increasing plasma catecholamines. Norepinephrine concentrations increased in both skin and lung and decreased in liver, pancreas, and scalp; those of epinephrine increased in the heart, lung liver, and scalp and decreased in the adrenal. There were only minor changes in brain catecholamine concentrations except for a 50% reduction in dopamine in the caudate nucleus. Concentrations of dopamine catabolite 3,4-dihydroxyphenylacetic acid decreased in many brain parts, suggesting that cerebral catecholamine metabolism was affected by hypoxemia and asphyxia. We conclude that the sympatho-adrenal system of fetal guinea pigs near term is mature and that its stimulation by reduced fetal oxygen supply leads to changes in both plasma and tissue catecholamine concentrations.     

Mechanism of action of 2-hydroxyestradiol on steroidogenesis in ovarian granulosa cells: interactions with catecholamines and gonadotropins involve cyclic adenosine monophosphate

Previously we have shown that 2-hydroxyestradiol (2-OH-E2) synergizes with catecholamines to enhance progesterone production by porcine granulosa cells in vitro. The present studies were undertaken to determine if the synergistic effects of 2-OH-E2 and catecholamines were 1) modulated by gonadotropins, 2) unique to catecholamines, and 3) mediated by cyclic adenosine monophosphate (cAMP). Undifferentiated granulosa cells from 1- to 3-mm porcine follicles were cultured in serum-free medium for periods of 6-9 days. A 3-day pretreatment plus a 4-day cotreatment versus a 4-day cotreatment of granulosa cell cultures with follicle-stimulating hormone (FSH) did not significantly alter progesterone production stimulated by a saturating concentration of epinephrine (EPI; 2 micrograms/ml) but significantly reduced the effect of 4 micrograms/ml 2-OH-E2 on Day 7 of culture. Four-day cotreatment of either FSH or luteinizing hormone (LH) from Day 3 to 7 of culture dramatically enhanced progesterone production stimulated by 2-OH-E2 and estradiol (E2) but not by EPI when measured on Day 7 of culture. Progesterone production (expressed as "-fold of controls") stimulated by 4-day treatment of EPI, 2-OH-E2, or EPI-plus-2-OH-E2 was 1.4 +/- 0.2, 8.2 +/- 2.2, and 10.7 +/- 1.0, respectively, in the presence of LH (n = 5 experiments), and 1.9 +/- 0.1, 7.8 +/- 1.4, and 10.6 +/- 1.8, respectively, in the presence of FSH (n = 3 experiments). Similar to E2, 2-OH-E2 significantly enhanced the stimulating effect of the cAMP analog 8-bromo-cAMP (0.5 mM) on progesterone production.(ABSTRACT TRUNCATED AT 250 WORDS)