Increase In Epinephrine Secretion Research Articles

On the mechanism of diazoxide-induced hyperglycemia.

Infusion of diazoxide (16.5 mg./kg. in 10 minutes) into normal unanesthetized dogs resulted in a prompt hyperglycemia due to increased hepatic glucose production as measured with a 3-3H-glucose primer-infusion technique. Plasma insulin and glucagon were decreased. Glucose uptake failed to increase. Diazoxide administration during period of alpha adrenergic receptor blockade with phentolamine still caused hyperglycemia and increased glucose production. Glucose uptake was inhibited despite adequate plasma insulin. Infusion of somatostatin along with insulin prevented the effects of diazoxide on plasma glucose and glucose production. It is concluded that diazoxide hyperglycemia is not due solely to decreased insulin secretion or increased epinephrine secretion and that glucagon is not a contributory factor. Diazoxide may act directly to increase glucose production and inhibit glucose uptake. Somatostatin appears capable of blocking the effect of diazoxide on glucose production by an unknown mechanism.

Effects of cholinergic drugs and their blockers on adrenaline release from rat adrenal

Effects of cholinergic agents and their blockers on adrenaline secretion from rat adrenal were investigated. Nicotine-induced adrenaline output was markedly prevented by hexamethonium. High doses of atropine (1·0 mg/kg, i.v.) also decreased nicotine-induced adrenaline secretion from splanchnicotomized adrenal. Acetylcholine (ACh) subsequent to neostigmine caused marked secretion of adrenaline, which was almost completely blocked by atropine pretreatment. However, ACh-induced adrenaline output from the splanchnicotomized adrenal was much less than that from the intact gland. The response of chronically and completely denervated adrenal to ACh was larger than that of the chronically or acutely splanchnicotomized gland. Pilocarpine increased adrenaline secretion and the output was prevented by pretreatment with atropine. In acutely splanchnicotomized rats, pilocarpine caused little increase of adrenaline secretion. Atropine (1·0 mg/kg, i.p.) caused a slight increase of adrenaline output in response to ether anesthesia, although methylatropine tended to inhibit output. Stimulation of the central end of the severed vagus at the cervical level had no effect on adrenaline liberation from splanchnicotomized adrenal with or without stimulation of splanchnic nerve. From these results, the sites of action of these drugs in rats are discussed.

Drug-Induced Adrenaline Release and Blood Glucose in Rats: 3-phenyl-5-(2-piperidinoethyl)-Isoxazole Citrate

The effects of 3-phenyl-5-(2-piperidinoethy1)-isoxazole citrate (31245) on blood glucose level and adrenaline release from the adrenal gland were studied in rats. Elevation of blood glucose was detected in intact and hypophysectomized rats, but not in adrenalectomized or adrenal-demedullated rats after s.c. injection of 31245. Increase of adrenaline release from the left adrenal after administration of 31245 was detected under pentobarbital anesthesia. In splanchnicotomized rats, no increase of adrenaline secretion was observed after administration of this compound. Pretreatment with 31245, 5 mg/kg i.v., prevented about 35% of the adrenaline output caused by electrical stimulation of the splanchnic nerve, though it had no inhibitory effect on adrenaline secretion caused by histamine and bradykinin. From these results, it is concluded that hyperglycemia induced by 31245 is due to hypersecretion of adrenaline from the adrenal glands through excitation of the splanchnic nerves, though its direct action on the gland is an inhibitory effect on adrenaline release.

Adrenaline and noradrenaline secretion of the adrenal gland in conscious dogs in response to pilocarpine and nicotine.

Conscious dogs were injected intravenously with 1.0mg/kg of pilocarpine or 0.3mg/kg of nicotine. Adrenal venous effluent was collected before and after the injection and analyzed for adrenaline and noradrenaline fluorimetrically. After the injection of pilocarpine a marked increase in adrenaline secretion with an inconsistent and slight increase in noradrenaline secretion was observed. Following the injection of nicotine the adrenaline and noradrenaline secretion increased markedly, the increase in the former being predominant.

Bulbar and suprabulbar control of the cardiovascular autonomic effects during arterial hypoxia in the rabbit.

The autonomic effects on heart rate, portal, renal, cutaneous and muscle blood flows were studied during approximately constant severe arterial hypoxia in unanesthetized sham-operated, thalamic and pontine rabbits, 3 hours after operations conducted under halothane anesthesia. Neural and adrenal effects were estimated by comparing the responses of different groups of animals: (a) with all neural effectors intact, (b) after adrenalectomy, (c) after selective and (d) after complete pharmacological block of neural effector mechanisms. In pontine animals hypoxia greatly increased cardiac sympathetic activity and seemed to evoke a greater release of adrenal catecholamine (epinephrine) than in other preparations, but caused significant neural peripheral sympathetic constrictor effects in only the portal bed. In thalamic animals, hypoxia caused reflex bradycardia, striking neural constrictor effects in the portal, renal and muscle beds, and cutaneous dilatation. There was little evidence of an increase in epinephrine secretion. It is suggested that there is an inhibitory pathway between diencephalon and bulb that limits the release of epinephrine. Sham-operated animals exposed to hypoxia secreted epinephrine which played an important role in the total reflex response; this group had similar cardioinhibitory and cutaneous effects to thalamic animals, but a more rapid onset of portal and renal constriction and a marked increase in muscle blood flow. The sympathetic responses of the different preparations resulted in different rates of metabolic H + ion production.

Studies of the importance of the thyroid and the sympathetic system in the defence to cold of the goat.

ABSTRACTMarkedly hypothyroid goats were found to retain the ability to maintain body temperature during acute cold exposure (‐ 3° C), and to react to local cooling of the hypothalamic thermoregulatory “centre” by a rise in body temperature. However, the shivering response to external cold and to hypothalamic cooling was strongly accentuated, and the increase in urinary excretion of cate‐cholamines (especially of adrenaline) was generally much greater than that of the euthyroid goat. In 3 out of 4 hypothyroid goats studied, the catecholamine excretion at room temperature was also higher than that found in euthyroid goats. During acute cold exposures the blood glucose of the hypothyroid goats rose by about 300 per cent as compared to a rise of about 20 per cent in the euthyroid animals. It is concluded that to maintain thermal homeostasis in the cold markedly hypothyroid goats have to compensate the lack of thyroid hormone by a conspicuous increase in adrenaline secretion. Bilateral splanchnicotomy in the euthyroid goat resulted in practically complete absence of adrenaline in the urine, but did not present the rise in body temperature and the shivering seen during local cooling of the anterior hypothalamus. However, the hyper‐glycemic response to hypothalamic cooling was blocked completely.

Effect of selected hexoses, of epinephrine and of glucagon on insulin secretion in man.

Immunochemical methods of measuring serum insulin have implemented studies in man confirming in vitro data which suggest that metabolizable sugars such as mannose and glucose cause insulin secretion, whereas galactose, a nonutilizable sugar, does not. Infusions of 2-deoxy-D-glucose are associated with greatly increased epinephrine secretion and sustained hyperglycemia, but no rise in serum insulin levels. Epinephrine infusions induce and prolong hyperglycemia without raising serum insulin levels and effectively inhibit insulin secretion during glucose administration. These findings agree with in vitro evidence that epinephrine directly inhibits pancreatic secretion of insulin. Glucagon, on the other hand, sharply stimulates insulin secretion, either alone or after glucose infusions. Data are presented which suggest that this may be a direct effect of glucagon on the release of insulin by the pancreatic beta cell.

Der Einflu� von Insulin auf den Kaliumtransport in der Skeletmuskulatur

The ability of insulin to increase the l-arabinose distribution volume in alloxan diabetic rats has been found decreased in 6-aminonicotinamide (6-AN) treated rats. The percentage decrease is equal to the impairment in the insulin dependent glucose transport. From this it has been concluded that the 6-AN induced impairment of the glucose diffusion facilitated by insulin is localized in the cellular membrane. Insulin plasma concentration has been found increased in 6-AN treated animals in response to an accelerated glycogenolysis mediated by an increase in epinephrine secretion. The increase in insulin secretion has been shown to cause an activation in potassium transport in skeletal muscle. Alloxan diabetic animals do not exhibit the stimulation in net cellular potassium uptake nor do adrenalectomized rats the plasma insulin concentration of which does not rise because of the lack in epinephrine mediated glycogenolysis. With especially high rates of epinephrine induced glycogenolysis plasma insulin concentration has been found to increase to a smaller degree than would be expected from the blood glucose concentration of these animals. In accordance to the results published byCoore andRandle (1964) andPorte, Graber, Kuzuya, andWilliams (1966) it is assumed that higher concentrations of epinephrine are capable to suppress insulin secretion in spite of an increase in blood glucose concentration.

Effect of myelencephalic stimulation on the secretion of noradrenaline and adrenaline of the adrenal gland in the cat.

The dorsal parts of the medulla oblongata in cats were stimulated electrically and the adrenal medullary response was directly evaluated. Adrenal venous blood was collected from cats anesthetized with sodium pentobarbital and was analyzed for noradrenaline and adrenaline by the fluorimetric method. Following stimulation of the inferior fovea a definite increase in noradrenaline secretion without any definite increase in adrenaline secretion was observed. Stimulation of some other parts of the floor of the fourth ventricle produced a definite increase in adrenaline secretion with or without an increase in noradrenaline secretion. In some cases a decrease in noradrenaline secretion was found. A rise of blood pressure producible by myelencephalic stimulation was not always accompanied with an increase in adrenal medullary secretion.

NEURAL PATHWAYS MEDIATING THE INCREASE IN ADRENAL MEDULLARY SECRETION PRODUCED BY HYPOGLYCEMIA.

SummaryInsulin-induced hypoglycemia produced a marked increase in epinephrine secretion in fasted dogs. The rise was not abolished by transection of the midbrain or cervical spinal cord. It was completely abolished by removal of the thoracic and upper lumbar spinal cord in 4 of 6 dogs studied. It was also blocked by localized resection of the fifth to seventh thoracic segments of the spinal cord, but not by removal of more caudal segments. These data indicate that the portion of the spinal cord above the seventh thoracic segment is the only part of the central nervous system which is essential in the dog for the increase in epinephrine secretion produced by insulin-induced hypoglycemia.

生体内家兎胃運動の薬理学的研究

I can find no record whatsoever of any investigation concerning the action of ephedrine on the movement of the stomach in situ. I have experimented with this action and have obtained very interesting results. The method used was similar to that employed in the previous reports. The results obtained are as follows: 1. Ephedrine in most cases, acts excitatively on the isolated stomach of the rabbit. Rarely, relaxation appears first and gradually turns to excitement. This excitement is not affected by atropine. 2. Administered, ephedrine may produce either of two effects, namely, excitement or relaxation, on the movement of the stomach in situ. In cases where relaxation occurred the result, in the case of isolated stomach, was invariably excitement. 3. This excitement also appears after the resection of the pneumogastric nerves. Upon the administration of atropine this action is strongly supressed. However, it would not do to conclude, merely from this, that this action is connected with the para-sympathetic nerves, since even if the atropine is administered first this excitement still appears; atropine relaxes the stomachic movement strongly; and atropine does not affect the excitement produced on the isolated stomach by ephedrine. 4. On resecting the pneumogastric nerves or the splanchnic nerves, or amputating the spinal cord, the relaxation of the movement of the stomach in situ attributive to ephedrine appears unchanged as in the case of a normal rabbit. 5. Following the preadministration of atropine, nicotine, luminal or ergotamine, ephedrine still produces relaxation of the movement of the stomach in situ. After an administration of a dosage of urethane, this relaxation is augmented. 6. After ligation of the celiac artery on rabbits producing this relaxation, ephedrine fails to produce this relaxation. 7. When both suprarenal glands are removed, the relaxation of the movement of the stomach in situ due to ephedrine, does not appear. 8. On injecting intravenously a dosage of ephedrine (or urethane) on rabbits producing this relaxation, an increase of adrenaline is observed in the blood. 9. Upon administering a dosage of urethane to rabbits producing this relaxation, the increase of adrenaline secretion from the suprarenal glands attributive to ephedrine is augmented. 10. Performing resection of the splanchnic nerves on those rabbits displaying relaxation, the increase of adrenaline secretion from the suprarenal glands caused by ephedrine and urethane administered separately or simultaneously, is equal to or more than (but not less than) that in the case of a normal rabbit. 11. The relaxation of the stomachic movement resulting from an injection of ephedrine is a peripheral action and the suprarenal glands are closely related to this. Ephedrine acting on the suprarenal glands, increases the adrenaline secretion which in turn causes the relaxation. Thus, this relaxation may be said to be the indirect action of ephedrine. The increase of adrenaline secretion caused by stimulation by ephedrine is a peripheral action, and neither the nerve center nor the splanchnic nerves are involved. [Cf. original(Japanese) p.227.]

SUPPOSED ROLE OF THE ADRENALS IN HYPERTENSION

Our experiments constitute part of an investigation on the alleged relation of the adrenal medulla to certain diseases, particularly diabetes mellitus and hypertension. The supposition of such a relation is a basis for the clinical practice of surgical intervention at the adrenals or roentgen irradiation of the adrenal region as a therapeutic measure. Therefore it is important to determine if possible whether this alleged relationship can be supported by unequivocal experimental evidence. The prevailing concept that increased epinephrine secretion from the adrenal glands has an important role in the etiology and the pathology of hypertension rests largely on the experimental basis for the theory of an function of the adrenals. In a discussion of their experiments on epinephrine secretion during emotional excitement, on which the well known emergency theory rests, Cannon and de la Paz 1 stated: Injected epinephrine is capable of inducing an atheromatous condition of the arterial