Showing papers on "Epinephrine published in 1985"

Hypokalemia from beta2-receptor stimulation by circulating epinephrine

Abstract: Beta 2-receptor stimulation is required for catecholamine-induced hypokalemia to occur. This hypokalemia is not mediated by insulin, renin or aldosterone. Catecholamine-induced hypokalemia can be prevented by selective beta 2 blockade, which does not abolish the inotropic effect of epinephrine.

Beta adrenergic-mediated vasodilator response to insulin in the human forearm.

Abstract: Insulin, in doses sufficient to cause systemic hypoglycemia, decreases vascular resistance; however, a vasoactive effect of insulin in humans, in the absence of hypoglycemia, is unknown. Venous occlusion strain gauge plethysmography was utilized to determine forearm blood flow (FBF) and forearm vascular resistance (FVR) during incremental intra-arterial infusion of insulin (0.1, 0.5 and 1.0 mU/kg/min) in seven normal subjects. With the increasing doses of insulin, FBF increased 55, 76 and 145% and FVR decreased 30, 42 and 58%, respectively. Systemic glucose concentration decreased only during the highest dose insulin infusion. In eight subjects who received insulin during euglycemic glucose clamping, FVR also decreased. Therefore, it was demonstrated that insulin dilates the forearm vasculature in the absence of hypoglycemia. In order to determine whether the vasodilatory effect of insulin was mediated by the sympathetic nervous system, plasma levels of epinephrine and norepinephrine were measured. During the incremental insulin infusions, norepinephrine levels did not change, but epinephrine concentration increased during the 1.0 mU/kg/min infusion when hypoglycemia developed. Furthermore, 21 subjects were pretreated with intra-arterial phentolamine, propranolol or the combination of phentolamine and propranolol. Phentolamine did not potentiate the fall in FVR during insulin administration; however, propranolol attenuated or completely inhibited the changes in FBF and FVR. During combined alpha and beta adrenergic blockade, insulin increased FBF and decreased FVR only during the higher dose insulin infusions. It is concluded that insulin causes forearm vasodilation primarily via a beta adrenergic mechanism. In addition, at the higher doses used in this study, insulin may decrease FVR directly or by a mechanism other than adrenergic stimulation.

Effect of exercise on epinephrine turnover in trained and untrained male subjects

Abstract: The kinetics underlying plasma epinephrine concentrations were studied. Six athletes (T) and six sedentary males (C) were given intravenous infusions of 3H-labeled epinephrine, after which arterial blood was drawn. They rested sitting and bicycled continuously to exhaustion (60 min at 125 W, 60 min at 160 W, 40 min at 200 W, and 240 W to the end). Work time was 154 +/- 13 (SE) (T) and 75 +/- 6 (C) min. At rest, epinephrine clearance was identical [28.4 +/- 1.3 (T) vs. 29.2 +/- 1.8 (C) ml . kg-1 . min-1], but plasma concentration [1.42 +/- 0.27 (T) vs. 0.71 +/- 0.16 (C) nmol . l-1] and, accordingly, secretion [2.9 +/- 0.7 vs. 1.5 +/- 0.4 nmol . min-1] were higher (P less than 0.05) in T than C subjects. Epinephrine clearance was closely related to relative work load, decreasing from 15% above the basal level at 30% of maximal O2 uptake (VO2 max) to 22% below at 76% of VO2 max. Epinephrine concentrations increased much more with work intensity than could be accounted for by changes in clearance and were, at exhaustion, higher (P less than 0.05) in T (7.2 +/- 1.6) than in C (2.5 +/- 0.7 nmol . l-1) subjects despite similar glucose, heart rate, and hematocrit values. At a given load, epinephrine clearance rapidly became constant, whereas concentration increased continuously. Forearm extraction of epinephrine invalidated use of blood from a cubital vein or a hand vein arterialized by hot water in turnover measurements. During exercise, changes in epinephrine concentrations reflect changes in secretion rather than in clearance. Training may increase adrenal medullary secretory capacity.

Review and survey of medicaments used with gingival retraction cords

Abstract: Data from a survey of 495 dentists indicate that most dentists used the mechanical-chemical method of gingival-deflection; 79.39% of those used cord containing epinephrine. It can be concluded that potentially significant amounts of epinephrine can be absorbed systemically from the local anesthetic solution, that secretion of endogenous epinephrine in response to stress occurs, often at levels sufficient to cause measurable changes in hemodynamic variables, and that absorption of epinephrine from impregnated strings occurs. The amount of absorption will vary with the exposure of the vascular bed, the length and concentration of the impregnated cord, and the length of time of application. It is possible that the actual total amount of circulating catecholamine would be cumulative, and the corresponding cardiovascular response would be related to the total amount of epinephrine in the bloodstream, regardless of the source. When the fact that we usually have inadequate data on the cardiovascular status of our patients is considered, as well as the tendency to make impressions of multiple prepared teeth, the continued use of epinephrine cord in dentistry must be viewed with alarm. Equally effective astringent gingival deflection agents such as alum, aluminum sulfate, and aluminum chloride exert no systemic effects. Therefore, there is little indication for use of epinephrine-containing retraction cords. Adequate medical evaluation, careful use of anesthetics that contain epinephrine, and sedative techniques when indicated will assure the safety of our patients.

Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans.

Abstract: To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.

Sympathetic-adrenal medullary and cardiovascular responses to acute cold stress in adult and aged rats

Abstract: In this study, adult (5 months) and aged (22 months) Fischer 344 (F-344) male rats were surgically prepared with chronic tail artery cannulae. Two days after surgery, rats were stressed by immersion in 12 degrees C water for 10 min. Blood samples (0.5 ml) were collected before and at timed intervals after cold immersion (0, 15 and 60 min) and were later assayed for content of norepinephrine and epinephrine. Consistent with earlier studies from this laboratory, there were no differences between ages in basal plasma levels of either catecholamine or in mean arterial pressure or core temperature. However, basal heart rates of aged rats were approximately 10% greater than values for adult rats. During cold immersion, aged rats had greater decrements in heart rate compared to adults but there were no age-related differences in mean arterial pressure or core temperature. Immediately following cold immersion, increments above basal values for plasma norepinephrine and epinephrine (4.2-4.6 and 11.8-14.1-fold, respectively) were similar for 5- and 22-month-old rats. However, in aged rats plasma norepinephrine was greater at 60 min post-immersion and plasma epinephrine was greater at 15 and 60 min post-immersion compared to values for adults.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of plasma catecholamines to acute metabolic and hormonal responses to injury in man.

Abstract: Plasma catecholamine concentrations in 40 patients shortly after accidental injury rose progressively with increasing severity of injury. Norepinephrine and epinephrine concentrations were unrelated other than by a common rise with severity; dopamine was closely related norepinephrine and not independently related to injury severity. Plasma glucose concentrations rose after injury; however, this was related only to the plasma epinephrine concentration and not independently to injury severity. Plasma lactate concentrations, in contrast, showed components related both to severity of injury and independently to norepinephrine and epinephrine concentrations. Plasma insulin concentrations were uniformly low, especially with respect to the hyperglycemia, in patients with high plasma epinephrine concentrations. Plasma concentrations of free fatty acids and of cortisol were unrelated to plasma catecholamine concentrations, as were pulse rate and blood pressure. These relationships confirm the expected role of the sympathoadrenal system in the metabolic changes following injury in man.

Role of epinephrine and vasopressin in the control of the pituitary-adrenal response to stress.

Abstract: In addition to corticotropin-releasing factor (CRF) and structurally related peptides, arginine vasopressin (AVP), oxytocin, angiotensin II, vasoactive intestinal polypeptide, peptide histidine isoleucinamide, epinephrine (E), and norepinephrine induce secretion of adrenocorticotropin (ACTH) from corticotropic cells in vitro. The apparent affinity and intrinsic ACTH-releasing activity of these substances are lower than those of CRF. These substances can also act synergistically with CRF. In this paper the role of catecholamines and AVP in the control of ACTH release is discussed. Infusion i.v. of E increases plasma ACTH and corticosterone to levels that are normally found during stress. E-induced stimulation of pituitary-adrenal activity is mediated by beta adrenoceptors and involves release of CRF, because it can be prevented by beta-adrenoceptor blockers and by destruction of CRF neurons (hypothalamic lesions), blockade of CRF release (chlorpromazine, morphine, and Nembutal), or administration of CRF antiserum. Although stress can cause a vast increase in plasma E, circulating E is not essential for the acute stress-induced release of ACTH because blockade of beta (or alpha) adrenoceptors, administration of chlorisondamine, or extirpation of the adrenal medulla and sympathectomy do not prevent the pituitary-adrenal response to stress. In contrast, circulating E plays a major role in the release of intermediate-lobe peptides during emotional stress. Studies of the role of AVP in pituitary-adrenal control by the use of pressor receptor (V1) antagonists are not valuable because of the ineffectiveness of such antagonists in blocking AVP-induced release of ACTH from corticotropic cells in vitro. Treatment of rats with an antiserum to AVP reduces the ACTH response to stress. We conclude that AVP has an important role in stress-induced activation of the pituitary-adrenal system, possibly by potentiating the effects of CRF.

Desensitization of alpha-1 adrenergic receptor-mediated vascular smooth muscle contraction.

Abstract: Desensitization of alpha-1 receptor-mediated smooth muscle contraction was studied in rabbit aorta. Incubation of rabbit aorta ring segments with epinephrine (10(-6) M) for 7 hr resulted in a 10-fold loss in sensitivity of the tissue to alpha-1 adrenergic receptor-mediated contraction with no change in maximal force of contraction. This loss in sensitivity was specific for alpha-1 receptor-mediated contraction because responses to histamine and serotonin were unchanged in these aortas. Conversely, prolonged exposure of vessels to histamine (10(-5) M) led to desensitization of histamine-mediated contraction without altering responses to alpha-1 receptor stimulation. Using [125I] BE2254, a potent alpha-1 receptor antagonist, the loss in sensitivity to catecholamines was found not to be mediated by down-regulation of alpha-1 receptors nor by a loss in their affinity for epinephrine. However, desensitization was associated with a blunting of alpha-1 receptor stimulation of phosphatidylinositol turnover. These results suggest that desensitization of alpha-1 receptor-mediated contraction in rabbit aorta does not appear to be mediated by changes in receptor number or affinity but may involve alterations in receptor coupling.

Serotonin Coexists with Epinephrine in Rat Adrenal Medullary Cells

Abstract: Immunoreactive serotonin is demonstrated to be present in 75% of rat adrenal medullary cells using an antibody to serotonin and peroxidase-antiperoxidase immunocytochemical method. The concentration of serotonin in rat adrenals was found to be 7.7 ± 0.1 × 10–6 mol/kg wet weight by high-performance liquid chromatography with electrochemical detection. Drugs that block serotonin synthesis (p-chlorophenylalanine) or deplete biogenic amines (reserpine) diminish immunostaining. The serotonin precursor .L·tryptophan and pargyline, a monoamine oxidase inhibitor, augment staining in reserpine-depleted adrenals. Serotonin is localized in those medullary cells which contain phenylethanolamine-N-methyltransferase, an enzyme which is necessary for the synthesis of epinephrine. We conclude, therefore, that serotonin coexists with epinephrine in rat adrenal medullary chromaffin cells. These results suggest that the adrenal medulla may play a major role in the metabolism of serotonin.

Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha 2 adrenoceptor properties.

Abstract: . Investigations were carried out to demonstrate the function and the possible advantage of the interplay between β1 and α2 adrenoceptor sites in the regulation of human subcutaneous fat-cell lipolysis. α2 and β adrenoceptor binding studies were conducted with antagonist radioligands and revealed that α2-adrenoceptors ([3H] yohimbine and [3H] rauwolscine binding sites) are more numerous than β1-adrenoceptors ([3H] dihydroalprenolol and [3H]CGP-12177 binding sites) in human fat-cell membranes. Physiological agonists epinephrine and norepinephrine competed with [3H]-ligand sites with a higher affinity for α2 sites than for β1 sites. Epinephrine exhibited a higher affinity than norepinephrine for the α2 sites; the two amines had the same affinity for β1 sites. In lipolysis studies conducted in the absence of adenosine deaminase the β lipolytic action of the biological amines predominated; after α2-adrenoceptor blockade by yohimbine or idazoxan, the amines exhibited an intrinsic activity similar to that of isoproterenol. When adenosine was prevented from accumulating in the incubation medium by inclusion of adenosine deaminase, low concentrations of epinephrine and norepinephrine preferentially exerted an antilipolytic action. We conclude that: (i) the lipolytic response in abdominal human subcutaneous fat cells to physiological amines results from the interplay between β1- and α2-adrenoceptor stimulation; (ii) α2- adrenoceptors, with their higher number and higher affinity for the physiological amines, and the adrenoceptor population involved at the lowest (i.e. physiological) concentrations of the amines; and (iii) the β1 sites with a lower number and weaker affinity for epinephrine and norepinephrine are involved when higher concentrations of the amines reach the plasma membrane. Thus, α2 adrenoceptors appear to be hormonal extrasynaptic receptors which control the state of activity of the human fat cell.

Pentobarbital effects on plasma catecholamines: temperature, heart rate, and blood pressure

Abstract: The effects of intravenous pentobarbital were studied in dogs. Plasma pentobarbital concentrations were inversely related to epinephrine and norepinephrine concentrations. Plasma catecholamines appeared fully suppressed at pentobarbital levels greater than 25-30 micrograms/ml. Furthermore, pentobarbital levels were negatively related to rectal temperature, heart rate, and mean blood pressure. The methods of pentobarbital administration influenced plasma pentobarbital as well as epinephrine and norepinephrine levels, temperature, heart rate, and blood pressure. These observations suggest the possibility that pentobarbital inhibits the sympathetic nervous system, which in turn may affect temperature, heart rate, and blood pressure. Because pentobarbital anesthesia affects plasma catecholamine concentrations, the regimen used in animal models requires consideration when interpreting data potentially influenced by the sympathetic nervous system.

Nervous control of the blood pressure in the Atlantic cod, Gadus morhua

Abstract: Dorsal (PDA) and ventral aortic blood pressure (PVA) and heart rate (HR) were measured in conscious resting cod, Gadus morhua L., which has been allowed 24 h recovery from surgery. Plasma adrenalin and nonadrenalin concentrations in these fish were 3.4 and 2.2 nmoll-1 respectively, and thus lower than previously reported values from partially recovered cod. Twenty-four hours after treatment with the adrenergic neurone blocking agent bretylium, PDA was significantly reduced by 17% compared to sham-injected controls, although PVA and heart rate were unaltered. Subsequent alpha-adrenoceptor blockade by phentolamine produced no further fall in PDA and no changes in PVA or HR, provided a 5-h period was allowed to overcome the acute toxic side effects of phentolamine. The effectiveness of the bretylium or phentolamine blockade was confirmed by noting the absence of any vasoconstrictor response during sympathetic nerve stimulation in perfused tails from fish used in the in vivo experiments. Bretylium had no significant effect on the sensitivity of the isolated coeliac artery to adrenalin, but effectively blocked the adrenergic innervation of this artery or the vasculature of the tail. Evidence for a non-selective blockade of non-adrenergic nerves to the heart was also obtained. It is concluded that the adrenergic tonus affecting the dorsal aortic blood pressure in resting cod that have recovered for 24 h following surgery is due solely to an adrenergic nervous tone.

Stress Hormones in Blood and Cerebrospinal Fluid of Conscious Sheep: Effect of Hemorrhage*

Abstract: Acute moderate hemorrhage (15 ml/kg withdrawn over 10 min) was used to study stress hormone changes in blood and cerebrospinal fluid (CSF) of conscious sheep with chronic indwelling intracerebroventricular catheters. Mean plasma arginine vasopressin (AVP) and ACTH rose 150- and 14-fold, respectively, above basal values to peak levels at 20 min after onset of hemorrhage. A smaller (4- to 5-fold) rise occurred in plasma angiotensin II (AII) to peak levels at 10 min. The corticosteroid response (cortisol and aldosterone) occurred later (peak at 45 min) and was consistent with the dependence of these steroids on plasma ACTH and AII changes. Increases in plasma epinephrine and norepinephrine were small and transient. Compared to changes in plasma, changes in CSF hormone levels after hemorrhage were small and independent of plasma concentrations. Mean CSF AVP increased to peak levels at 15 min whereas rises in CSF ACTH, AII-like immunoreactivity, and cortisol were slower and delayed in comparison with the patterns observed in plasma. Despite evidence of increased sympathetic activity, and rise in plasma catecholamines, CSF epinephrine fell after hemorrhage and CSF norepinephrine did not change. These results show that in conscious sheep rapid and major increases in plasma AVP, ACTH, and AII follow acute moderate hemorrhage. Concomitant changes in CSF hormone levels are small and delayed. With the possible exception of AVP it appears unlikely that the acute systemic hormone response to hemorrhage is determined by hormone changes in CSF.

Subtype-Selective Down-Regulation of Rat Renal Cortical α-and β-Adrenergic Receptors by Catecholamines*

Abstract: In the current studies, we have explored agonist-mediated down-regulation of adrenergic receptors in vivo. We infused catecholamines from sc implanted osmotic minipumps and examined the effects of the resultant increases in circulating levels of catecholamines on rat renal cortical alpha- and beta-adrenergic receptor subtypes, as assessed in radioligand binding studies. Infusion of epinephrine or norepinephrine (at 150 micrograms/kg X h) elevated plasma levels of each catecholamine 10- to 20-fold and decreased renal cortical alpha 1-receptor number about 50% without changing alpha 2-receptor number. Isoproterenol infusion (150 micrograms/kg X h) raised plasma levels of this catecholamine, but had no effect on the number of either alpha 1- or alpha 2-receptors. Renal cortical beta-adrenergic receptor number was decreased by infusion of all three catecholamines. However, the beta 1- and beta 2-adrenergic receptors were altered selectively by the different agonists. Infusion of norepinephrine decreased both beta 1- and beta 2-receptor number, but was more effective for the beta 1-receptors; this result was somewhat at variance with that we previously reported for rats bearing transplanted pheochromocytomas. The decrease in beta-receptor number due to epinephrine infusion was largely due to loss of the renal cortical beta 2-receptors. Infusion of isoproterenol decreased the number of both beta 1- and beta 2-receptors (69% and 75%, respectively). Infusion of norepinephrine maximally decreased the number of alpha 1-, beta 1-, and beta 2-receptors within 2 days, and the t 1/2 for receptor loss was about 12 h. beta-Receptors lost in response to isoproterenol infusion could not be recovered in a pellet prepared by high speed centrifugation of the supernatant derived from the preparation of renal cortical membranes. These results indicate that adrenergic receptor subtypes are differentially down-regulated by elevated levels of circulating catecholamines and that this differential loss of receptors depends on the nature of the receptor subtype, the agonist, and perhaps also whether catecholamines are infused rather than increased by pheochromocytoma.

Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics.

Abstract: The effects of epidural bupivacaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid-base status, and Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 32 parturients during labor and delivery. Patients in group I (n = 16) received 0.5% bupivacaine with 1:300,000 epinephrine and those in group II (n = 16) received 0.5% bupivacaine alone. Addition of epinephrine to bupivacaine had no significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate and variability, or the incidence of abnormal fetal heart rate patterns. Maternal hypotension occurred less frequently in group I than in group II patients (P less than 0.05). Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II (186.8 +/- 11.6 vs 85.3 +/- 6.1 (mean +/- SEM) min, P less than 0.001). It is concluded that adding epinephrine to bupivacaine during epidural anesthesia in the normal parturient has no adverse effects on either mother, fetus, neonate, or the progress of labor; and that it significantly prolongs the duration of anesthesia and decreases the incidence of maternal hypotension.

Expression of both alpha 1- and alpha 2-adrenoceptors in an insulin-secreting cell line. Parallel studies of cytosolic free Ca2+ and insulin release.

Abstract: Changes in intracellular free Ca2+, [Ca2+]i, and immunoreactive insulin release in response to alpha-adrenergic agents were measured in RINm5F cell suspensions. Cells were loaded with the fluorescent indicator quin 2 for monitoring [Ca2+]i. Epinephrine (1 microM), which inhibited alanine-stimulated insulin release by 73%, evoked a transient rise in [Ca2+]i. This rise is in part due to Ca2+ mobilization, since it is still present in the absence of extracellular Ca2+. The alpha 2-adrenergic agonist clonidine (10 microM) mimicked the epinephrine effect on insulin release without any change in [Ca2+]i. In contrast, the alpha 1-adrenergic agonist phenylephrine (10 and 100 microM) raised [Ca2+]i, albeit to a lesser extent than epinephrine. Phenylephrine enhanced basal, but had no effect on alanine-stimulated insulin release. To examine further the nature of the effect of epinephrine, specific alpha-adrenergic blocking agents were employed. The epinephrine-induced increase in [Ca2+]i could be inhibited by the alpha 1-adrenergic antagonists BE2254 (0.1 microM) and prazosin (0.01 microM). In the presence of these blockers, epinephrine was still able to inhibit insulin release. When alpha 2-adrenergic receptors were blocked by the addition of idazoxan (0.1 and 1 microM), epinephrine still raised [Ca2+]i. At the higher concentration of idazoxan, the epinephrine inhibition of insulin release was completely overcome. The alpha-adrenergic agonists did not attenuate the alanine-induced rise in [Ca2+]i. This study shows that both subtypes of alpha-adrenergic receptors are present in the insulin-secreting cell line RINm5F. The activation of alpha 1-adrenergic receptors leads to an increase in [Ca2+]i. In contrast, the inhibition of insulin release due to epinephrine is mediated through alpha 2-adrenergic receptors. The alpha 2-adrenergic mechanism does not involve changes in [Ca2+]i, but is rather exerted at a later step in the secretory process.

β-Adrenergic Stimulation of Aldosterone Production by Rat Adrenal Capsular Explants*

Abstract: Adrenal glomerulosa was examined for the presence of an adrenergic influence on aldosterone production. Cultured rat adrenal capsular explants were transferred to a perifusion system where the effect of exposure to catecholamines on aldosterone production was assessed. At 10(-6) M, isoproterenol greater than epinephrine greater than norepinephrine significantly stimulated aldosterone production, whereas at 10(-8) M only isoproterenol showed significant stimulation. Propranolol, a beta-adrenoreceptor antagonist, inhibited stimulation by epinephrine, and the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine, enhanced stimulation by a submaximal dose of epinephrine. Epinephrine and norepinephrine were found by radioenzymatic assay to be present in fresh as well as cultured capsular tissue, although levels were considerably lower in tissue that had been in culture (about one tenth that of fresh tissue). The epinephrine-norepinephrine ratio was similar in capsule and medulla, suggesting a medullary source of capsular catecholamines. Whether catecholamines in the capsule arose from the in vitro manipulation of adrenal tissue or existed in vivo is unclear. In summary, beta-agonists stimulate aldosterone production in cultured rat capsular explants.