Adrenal Medullary Catecholamine Release Research Articles

Tyrosine intake and cardiovascular responses in a motivated performance situation.

Ingesting the catecholamine precursor tyrosine can prevent decrements in, or improve, cognitive and motor performance in demanding situations. Furthermore, the biopsychosocial model of challenge and threat specifies that adrenal medullary catecholamine release plays a central role in the occurrence of a challenge state, which has been linked to better performance under pressure than a threat state. The present study thus examined whether acute tyrosine intake impacts upon challenge and threat states or influences cognitive and motor performance independently. A double-blind randomised crossover design with 49 participants (33 males; µage = 22.5 years, SD = 5.0) was used. Participants ingested tyrosine or placebo (150mg/kg body mass) 60 minutes before performing the N-Back task and a bean-bag throwing task. Cognitive self-reports and cardiovascular data before each task provided indicators of challenge and threat states. There were no significant differences between tyrosine and placebo on the cognitive and cardiovascular challenge and threat variables. Generalised Estimating Equations analyses found that tyrosine was associated with better performance than placebo on the bean-bag throwing task, but not on the N-Back task. A significant interaction effect showed that challenge and threat states were more positively related to performance in the placebo condition than in the tyrosine condition. This suggests that tyrosine may have attenuated the detrimental effect of a threat state. The present study breaks new ground in relating the impact of a dietary supplement to challenge and threat states and finding that tyrosine may in some cases attenuate the negative effects of a threat state.

Choline, CDP-choline or phosphocholine increases plasma glucagon in rats: Involvement of the peripheral autonomic nervous system

The present study was designed to test the effects of choline, cytidine-5′-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200–600 μmol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pretreatment with hexamethonium (15 mg/kg; i.p.), a peripherally-acting ganglionic nicotinic acetylcholine receptor antagonist, entirely blocked the increases in plasma glucagon by 600 μmol/kg of choline, CDP-choline or phosphocholine. The increases in plasma glucagon by these choline compounds was reduced significantly (P<0.01) by about 25% by pretreatment with atropine methylnitrate (2 mg/kg), a peripherally-acting muscarinic acetylcholine receptor antagonist. Blockade of central acetylcholine receptors did not alter the increase in plasma glucagon induced by i.p. choline (600 μmol/kg). While α2-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of α1- or β-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 μmol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 μg; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 μg; i.c.v.). These data show that choline, CDP-choline or phosphocholine increases plasma glucagon concentrations by increasing peripheral nicotinic and muscarinic cholinergic neurotransmissions. Central choline also increases plasma glucagon by augmenting central nicotinic cholinergic neurotransmission by acting presynaptically. Stimulation of adrenal medullary catecholamine release and subsequent activation of α2-adrenoceptors are mainly involved in the increase in plasma glucagon induced by choline, CDP-choline or phosphocholine.

Bee venom injection produces a peripheral anti-inflammatory effect by activation of a nitric oxide-dependent spinocoeruleus pathway

Our recent data, obtained using a zymosan-induced inflammatory air pouch model in mice, have demonstrated that subcutaneous bee venom (BV) injection into the hind limb selectively activates the contralateral brain stem locus coeruleus (LC) and then via a descending noradrenergic pathway and subsequent adrenal medullary catecholamine release induces a potent anti-inflammatory effect. While the efferent limb of this BV-induced neuroimmune anti-inflammatory pathway is well documented, the afferent limb of this pathway is poorly understood. In particular the spinal mechanisms involved with BV activation of the LC are currently unknown. Spinal nitric oxide (NO) and its synthase (NOS) have been shown to play an important role in the transmission and amplification of neuronal information from the spinal cord to the brain stem. In the present study we evaluated whether spinal NO plays a role in BV-induced LC activation, since we have previously shown that LC activation underlies this 'BV-induced anti-inflammatory effect' (BVAI) using the mouse air pouch model. Intrathecal (i.t.) pretreatment with l-nitro arginine methyl ester (l-NAME, non-selective NOS inhibitor), hemoglobin (NO scavenger) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, soluble guanylate cyclase inhibitor) abolished BVAI on zymosan-induced leukocyte migration into the air pouch. Moreover, i.t. injection of l-N-iminoethyl-lysine (l-NIL, inducible NOS inhibitor), but not 7-nitroindazole (7-NI, neuronal NOS inhibitor), also inhibited BVAI. BV injection significantly increased both the number of Fos immunoreactive neurons and tyrosine hydroxylase-Fos double labeling neurons in the contralateral LC in zymosan-induced inflamed mice. Importantly this increase in Fos expression in the LC was also completely inhibited by i.t. injection of l-NIL, but not by i.t. injection of 7-NI. Collectively these results indicate that spinal NO generated from inducible NOS is involved in the BV-induced LC activation that underlies BVAI.

Intraperitoneal administration of choline increases serum glucose in rat: involvement of the sympathoadrenal system.

Intraperitoneal injection of choline (40, 80 or 120 mg/kg) produced a dose-dependent increase in serum glucose and choline levels in rats. The increases in serum glucose and choline were associated with an increase of serum insulin as well as plasma levels of epinephrine and norepinephrine. The increases in serum glucose and plasma catecholamine concentrations induced by choline (120 mg/kg) were blocked by pretreatment with the ganglionic nicotinic receptor antagonist hexamethonium (15 mg/kg), but were not affected by pretreatment with atropine (5 mg/kg). The choline-induced rise in serum insulin was blocked by pretreatment with atropine and with hexamethonium each. The increase in serum glucose evoked by choline (120 mg/kg) was blocked by alpha-adrenoceptor blockade and bilateral adrenalectomy each. Blockade of beta-adrenoceptor by propranolol or chemical sympathectomy by 6-hydroxydopamine failed to alter the hyperglycemic response to choline. These results show that choline, a precursor of the neurotransmitter acetylcholine, increases serum glucose and insulin levels. The effect of choline on serum insulin is mediated by both muscarinic and nicotinic acetylcholine receptors, whereas the effect of choline on serum glucose is mediated solely by nicotinic receptors. The stimulation of adrenal medullary catecholamine release and subsequent activation of alpha-adrenoceptors apparently mediates the hyperglycemic effect of choline.

Endothelin enhances and inhibits adrenal catecholamine release in deoxycorticosterone acetate-salt hypertensive rats.

Endothelin (ET) and the sympathoadrenal system contribute to the development and maintenance of deoxycorticosterone acetate (DOCA)-salt hypertension. ET can act directly on the adrenal medulla to enhance the release of catecholamines. In addition, the level of ET peptide is increased in the adrenal glands of DOCA-salt hypertensive rats. Therefore, we tested the hypothesis that ET enhances adrenal medullary catecholamine release during DOCA-salt hypertension. The infusion of exogenous ET-1 into an isolated, perfused adrenal gland preparation resulted in an increase in the basal release of norepinephrine (NE) and epinephrine (EPI) in control and DOCA-salt hypertensive rats. Nerve-stimulated (0.3 Hz) release of NE was significantly inhibited during ET-1 infusion in the DOCA-salt hypertensive rats but not in the control rats. The role of endogenous ET on basal and nerve-stimulated NE and EPI release was also examined. An infusion of either BQ-123 (10(-7) mol/L), an ET(A) receptor antagonist, or BQ-788 (10(-7) mol/L), an ET(B) receptor antagonist, did not alter basal NE or EPI release in either control or DOCA-salt hypertensive rats. BQ-788 did not alter nerve-stimulated release of NE and EPI. In contrast, the nerve-stimulated release of EPI, but not NE, was enhanced during BQ-123 infusion in DOCA-salt hypertensive rats. Nerve-stimulated NE and EPI release was unaffected by BQ-123 in the control rats. These data suggest that ET can stimulate adrenal medullary catecholamine release in normotensive and DOCA-salt hypertensive rats. However, ET also inhibits adrenal medullary catecholamine release in DOCA-salt hypertensive rats.

Structural remodelling of the heart by fibrous tissue: role of circulating hormones and locally produced peptides.

Symptomatic heart failure is accompanied by diastolic ventricular dysfunction due largely to an extensive reactive and reparative fibrosis. Experimental evidence suggests a clear association between myocardial fibrosis and chronic inappropriate elevations in circulating angiotensin II (Ang II) and/or aldosterone. Although not entirely elucidated, injury follows Ang II-associated release of adrenal medullary catecholamines and aldosterone-induced myocardial potassium depletion. Increasing evidence indicates locally produced cardiac Ang II plays an important role in tissue repair that may underlie myocardial remodelling, the fibrous tissue accumulation both at and remote to the site of myocardial infarction (MI). Angiotensin converting enzyme (ACE) binding density markedly increases at these fibrous tissue sites after experimental MI, indicating an involvement in wound healing regardless of the cause and location of fibrosis; cells expressing Ang II receptors are primarily myofibroblasts. Therapy with ACE inhibitors and aldosterone receptor antagonist have each been shown to attenuate development of fibrosis.

Decreased adrenal medullary catecholamine release in spontaneously diabetic BB-Wistar rats. Role of hypoglycemia

Decreased adrenal medullary catecholamine release in spontaneously diabetic BB-Wistar rats. Role of hypoglycemia

Decreased Adrenal Medullary Catecholamine Release in Spontaneously Diabetic BB-Wistar Rats: Role of Hypoglycemia

We have demonstrated previously that spontaneously diabetic BB-Wistar rats exhibit decreased adrenal medullary catecholamine secretion in response to splanchnic nerve terminal stimulation. We hypothesized that this abnormality is caused by changes in the sensitivity of the adrenomedullary chromaffin cells to acetylcholine (ACh). To study this hypothesis, we isolated adrenal glands from control and spontaneously diabetic BB-Wistar rats, perfused them with ACh, and measured catecholamine secretion. Adrenal catecholamine release in response to ACh was significantly decreased at 2, 8, and 16 weeks after the onset of diabetes compared with age-matched, nondiabetic control rats. Catecholamine release in response to perfusion with 20 mM K+ was the same in adrenals from diabetic and control rats. The decreased responsiveness of diabetic rat adrenals to perfusion with ACh was significantly correlated with a decrease in the release of catecholamines in response to splanchnic nerve stimulation. A similar defect in catecholamine secretion was also seen in adrenals harvested from nondiabetic BB-Wistar rats following a 3-h period of acute hypoglycemia; however, the adrenal response to potassium was also decreased as was the catecholamine content of the adrenal. Conversely, nondiabetic BB-Wistar rats made diabetic with streptozocin (STZ) and maintained in a hyperglycemic state did not exhibit catecholamine hyposecretion 2 weeks after STZ administration. Collectively, the data describe decreased adrenomedullary response to cholinergic stimulation in spontaneously diabetic rats as early as 2 weeks after the onset of diabetes and that a similar, although more severe, hyposecretion occurs after acute, severe hypoglycemia.

Hypertensive mechanisms and converting enzyme inhibitors

The introduction of angiotensin-converting enzyme (ACE) inhibitors marks a new era in the understanding and treatment of high blood pressure. Although the benefits of therapy with ACE inhibitors are documented, it is more difficult to isolate the principal mechanisms that account for their effective actions in the treatment of hypertension. Recent data suggest that these agents affect both the pressor and depressor mechanisms that regulate vascular tone and cardiac function. For example, ACE inhibitors decrease angiotensin II-mediated vasoconstriction, reduce adrenal medullary catecholamine release, restore baroreceptor activity, and normalize vasomotor sympathetic activity. Experimental work indicates that ACE inhibitors also act on hypertensive mechanisms via actions on the central nervous system. Cardiovascular centers in the brain have receptor sites for angiotensin II and contain the proteins required for local synthesis of angiotensins. Vasomotor neurons possess such receptors and exhibit ACE activity. In addition, angiotensin II receptors involved in the regulation of baroreceptor activity are present in neuronal elements of the baroreflex arc. It is suggested that ACE inhibitors reach the brain via circumventricular organs to reduce sympathetic activity and enhance baroreceptor sensitivity. New studies suggest that depressor actions of ACE inhibitors include enhanced biosynthesis of vasodilator prostaglandins. From animal experiments it is deduced that enhanced production of angiotensin-(1-7) after inhibition of ACE stimulates release of vasodilator prostaglandins. These investigations clarify the function of tissue renin-angiotensin systems in the control of blood pressure in both normal and hypertensive states.

Role of the adrenal medulla in stress-induced hyperinsulinaemia in normal mice and in mice infected with Bordetella pertussis or treated with pertussis toxin.

Intranasal infection of mice with a sublethal dose of Bordetella pertussis or the intravenous administration of purified pertussis toxin resulted in a marked increase in the serum immunoreactive insulin concentration following ether stress. This stress-induced hyperinsulinaemia was not modified significantly by blockade of alpha 2-adrenoceptors with idazoxan, beta-adrenoceptors with propranolol, autonomic ganglia with hexamethonium, opioid receptors with naloxone, muscarinic cholinoceptors with atropine or by adrenal demedullation. The effect of pertussis in promoting stress-induced hyperinsulinaemia was mimicked qualitatively by alpha 2-adrenoceptor blockade, adrenal demedullation or ganglionic blockade. However, the serum immunoreactive insulin response to ether stress was smaller in animals subjected to these procedures compared with the response seen in mice infected with B. pertussis or treated with pertussis toxin. Thus, in the mouse, acute stress produces hyperinsulinaemia under conditions in which the release of adrenal medullary catecholamines is prevented, or the inhibitory action on insulin secretion is blocked by alpha 2-adrenoceptor antagonists or by pertussis toxin.

Angiotensin binding sites in the adrenal gland of the tree shrew

Release of adrenal medullary catecholamines is under neuronal and humoral control. Among many factors, angiotensin II (All) has been proposed to play a modulatory role [1]. It induces release of catecholamines from the adrenal medulla [2], probably through action on specific All receptors [3]. By in vitro receptor autoradiography, high-affinity receptors have been demonstrated in the rat adrenal medulla using the All agonist 125I-[Sar1]-AII [4]. This ligand showed specificities similar to those of 125I-AII and cross-displacement in binding experiments. These characteristics made the [Sar1]-AII analogue a suitable ligand for All binding sites studies.

High-affinity angiotensin receptors in rat adrenal medulla

Angiotensin II receptors have been quantitated in single rat adrenal medullas by incubation of tissue sections with 125I-[Sar 1]-AII, autoradiography with exposure to 3H-sensitive Ultrofilm, computerized densitometry and comparison with 125I-labelled standards. Rat adrenal medulla contains a single class of high affinity AII receptors with a K a of 0.84 ± 0.02 × 10 9 M −1 and a B max of 3259 ± 502 fmol/mg protein, one of the highest densities in AII receptors found in rat tissues. These observations provide evidence for a local site of action of AII in the release of adrenal medullary catecholamines.

The role of adrenal medullary catecholamine release in the response to a cold pressor test

We studied the effects of a cold pressor test on the plasma catecholamine levels of ten patients undergoing coronary angiography, to determine whether the pressor changes were related to adrenergic activity. To investigate the relative contribution of adrenal medullary catecholamine release, we subjected two adrenalectomised volunteers to the same test. Arterial blood was assayed for dopamine (DA), adrenaline (A) and noradrenaline (NA). We found significant rises in the levels of all three catecholamines in the angiography patients, accompanied by a significant elevation in arterial blood pressure. In both the adrenalectomised patients a rise in blood pressure was seen but no significant rise in plasma catecholamines could be demonstrated. We postulate that although adrenal medullary catecholamine release occurs in response to the cold pressor test, the blood pressure elevation is independent of such adrenal activity. Sampling radial arterial blood may not reflect changes in plasma levels of peripherally released NA.

Effects of 2-deoxy-D-glucose on the cardiac sympathetic nerves and the adrenal medulla in the rat: further evidence for a dissociation of sympathetic nervous system and adrenal medullary responses.

In rats and mice, fasting suppresses and sucrose overfeeding stimulates sympathetic nervous system (SNS) activity. Fasting hypoglycemia in rats suppresses SNS activity while stimulating adrenal medullary catecholamine release. Administration of 2-deoxy-D-glucose (2-DG), an inhibitor of intracellular glucose metabolism, also stimulates the adrenal medulla. The studies reported here were undertaken to determine the SNS response to chronic 2-DG administration and to test the hypothesis that diet-induced changes in SNS activity are related to central nervous system glucose metabolism. Ingestion of 2-DG caused an increase in urinary epinephrine excretion and significant depletion of adrenal epinephrine content, both indices of adrenal medullary stimulation. Chronic sc injections of 2-DG in animals with normal or increased food consumption caused simultaneous suppression of cardiac sympathetic nerve activity, as evidenced by diminished cardiac [3H]norepinephrine turnover, and stimulation of adrenal medullary epinephrine release. Parenteral 2-DG administration to adrenalectomized rats also caused suppression of cardiac sympathetic activity. Thus, this response to neuroglycopenia is independent of adrenal medullary catecholamine release. These results indicate that central nervous system glucose metabolism may mediate diet-induced changes in SNS activity.

Arterial hypertension elicited either by lesions or by electrical stimulations of the rostral hypothalamus in the rat

Bilateral anodal lesions performed with stainless steel electrodes placed either in the anterior medial (AMH) or lateral (ALH) hypothalamus, or in the ventromedial nucleus (VMH), induced in unrestrained rats the rapid development of arterial hypertension, tachycardia and death. Similarly placed cathodal lesions performed with platinum electrodes failed to elicit the cardiovascular syndrome. The electrical stimulation of the AMH, ALH or VMH caused an increase in the arterial blood pressure in anesthetized rats. This pressor response was characteristically biphasic and consisted of a sharp increase in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulation. The hypertension evoked either by lesions or by stimulations of the hypothalamus, appeared to depend largely on a neurally mediated release of adrenal medullary catecholamines, and to some extent on the activation of the sympathetic vasoconstrictor fibers. Bilateral adrenalectomy, or adrenal demedullation, prevented the hypertension evoked by lesions, and selectively blocked the important secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the sympathetic vasomotor axons with 6-hydroxydopamine (6-OHDA). On the other hand, the tachycardia evoked by lesions or stimulations of the medial hypothalamus, resulted from an increase in sympathetic neural discharges to the heart, and it was abolished either by β-receptor blockade with sotalol or by chemical sympathectomy with 6-OHDA. In contrast, the tachycardia occurring after lesions of the lateral hypothalamus was entirely due to circulating adrenal medullary catecholamines and it was eliminated by adrenalectomy. It is concluded that acute hypertension and tachycardia produced by anodal lesions performed with stainless steel electrodes results from the excitation of the hypothalamus, possibly due to the irritative action of the metallic ions deposited at the lesion sites. The observations of cardiovascular responses entirely due to adrenomedullary secretions suggests that the control of the adrenal medulla is at least partially distinct from that of the sympathetic vasoconstrictor and cardiac fibers, at the rostral hypothalamic level.

Inhibition of Adrenal Medullary Catecholamine Secretion by Enflurane

To determine the site and mechanism of action underlying the inhibition of adrenal medullary catecholamine release by enflurane, the authors measured the effects of enflurane on catecholamine secretion evoked by various secretagogues in isolated bovine adrenals perfused with Locke's solution. Catecholamine concentrations in the perfusate were measured spectrofluorometrically. Enflurane caused concentration-dependent inhibition of catecholamine release in response to activation of the nicotinic receptors in the chromaffin cells with acetylcholine or dimethylphenylpiperazinium (DMPP). An enflurane concentration of 0.88 mM caused 50 per cent inhibition of the DMPP-induced secretion. The inhibition induced by enflurane was shown to be noncompetitive. The catecholamine release evoked by activation of the muscarinic receptors with pilocarpine was only slightly decreased by 3.74 mM enflurane. At this concentration the release in response to KCl, 56 mM, was partially inhibited, whereas the output in response to tyramine (from glands perfused with calcium-free Locke's solution) was unaffected. It is concluded that the site of action of enflurane is the cell membrane. At concentrations above 1 mM, enflurane may impair calcium ion influx, but at lower concentrations it probably interacts with hydrophobic regions of the nicotinic receptor.

Blood pressure responses to adrenal field stimulation as a measure of adrenal catecholamine release.

1 A new method for studying adrenal medullary release is described in pithed rats using field stimulation of an entire adrenal gland. 2 The increases in blood pressure in response to field stimulation of the gland consisted of an initial short, variable component, due to stimulation of adrenergic vasomotor neurones and a secondary, longer lasting component, due to medullary catecholamine release. 3 Removal of the initial component by drugs or cardiac/coeliac ganglionectomy did not affect the magnitude of the secondary pressor component. 4 The secondary pressor component was frequency-dependent, reproducible and stable with time. The extent of medullary catecholamine release could be assessed by comparing the blood pressure rise with those obtained after adrenaline injections. 5 The method appears to provide a reliable means by which adrenal medullary catecholamine release may be assessed without significant interference from vasomotor nerves.

Fulminating arterial hypertension with pulmonary edema from release of adrenomedullary catecholamines after lesions of the anterior hypothalamus in the rat.

Bilateral electrolytic lesions of the anterior hypothalamus in unrestrained rats resulted in the development, within 2 hours, of arterial hypertension, tachycardia, hyperthermia, and increased locomotor activity, often leading to pulmonary edema and death. Similar lesions in paralyzed, artificially ventilated rats produced comparable changes in arterial blood pressure and body temperature with a similar time course. The arterial hypertension was a consequence of an increase in total peripheral resistance to 15% of control with a reduction in cardiac output to 49% of control. Arterial hypertension, elevated peripheral resistance, and diminished cardiac output were reversed toward normal by alpha-receptor blockade with phentolamine (1 mg/kg, iv). Bilateral adrenalectomy, adrenal demedullation, or adrenal denervation performed prior to lesion placement prevented the development of arterial hypertension and pulmonary edema as well as the changes in peripheral resistance, cardiac output, and body temperature. We conclude that arterial hypertension following lesions of the anterior hypothalamus is due to a neurally mediated increase in peripheral resistance initiated by the release of adrenal medullary catecholamines and that pulmonary edema is due to myocardial failure secondary to the ensuing ventricular overload. Structures originating in or passing through the anterior hypothalamus may exert selective control over the adrenal medulla independent of vasomotor neurons.

Effects of theophylline and propranolol on acetylcholine-induced release of adrenal medullary catecholamines

The effect of theophylline and propranolol on acetylcholine-induced catecholamine release was studied in isolated bovine adrenals perfused in vitro. The catecholamine release induced by half maximum dose of acetylcholine, 10 −4 M, was potentiated about 140 per cent by the presence of 1 mM theophylline in the perfusion medium. Theophylline enhanced the release of adrenaline but had little effect on the release of noradrenaline. The augmentary effect of theophylline on the adrenaline release was partially reduced by 10 −7 M atropine and by 10 −6 M propranolol. Propranolol by itself at a concentration of 10 −7 M, at which it had no membrane-stabilizing effect, reduced the acetylcholine induced secretion about 20 per cent. Propranolol had a greater inhibitory effect on the release of adrenaline than on noradrenaline. It is concluded that theophylline affected the release of adrenaline by mobilization of intracellular calcium stores and by preventing breakdown of cyclic AMP synthesized in response to stimulation of a β-adrenergic receptor located in the adrenalinestoring cells. A possible action of theophylline on cyclic GMP synthesized in response to stimulation of the muscarinic receptor is discussed.

A study of hypertension. The actions of synthetic angiotensin II on adrenal and myocardial catecholamines.

Several recent investigations have presented indirect evidence that angiotensin stimulates the release of adrenal medullary catecholamines. The following work was undertaken to elucidate the angiotensin action on the adrenal medulla and effect of myocardial catecholamines through observations of the changes in the adrenal and myocardial catecholamines caused in the rat by angiotensin injection. An injection of 0.5μg/kg body weight of angiotensin into the coccygeal vein brought about a significant decrease in adrenal noradrenaline after 3 minutes and also a significant decrease in adrenal adrenaline after 10 minutes. On the other hand, myocardial noradrenaline rose significantly. These results show that angiotensin is an effective stimulant for adrenal medullary cate-cholamines, and also angiotensin causes an increase in myocardial catecholamine, or noradrenaline, in particular.