High Concentrations Of Noradrenaline Research Articles

Regional concentrations of noradrenaline and dopamine in rat brain

The concentrations of noradrenaline and lopamine of 92 brain regions have been measured by a radiometric method which enabled discrimination between noradrenaline and adrenaline. Almost all brain regions investigated contained both noradrenaline and lopamine in measurable amount. However, both catecholamines appeared to be unevenly distributed. Very high dopamine concentrations were measured in the olfactory tubercle, the nucleus accumbens, the caudate nucleus and the rostral part of the medial forebrain bundle; the globus pallidus, the nucleus tractus diagonalis and the nucleus septalis lateralis were also very rich in dopamine. Outside the telencephalon the dopamine concentrations were rather low, except in the median eminence and the area tegmentalis ventralis (Tsai), an area corresponding to the A10 region. High noradrenaline concentrations were measured in most hypothalamic nuclei. Relatively high concentrations of this catecholamine were also measured in several mesencephalic (the ventral part of the central gray, the nucleus raphe dorsalis and the nucleus cuneiformis) and pontine (the locus coeruleus and the nuclei parabrachiales) regions. The highest noradrenaline concentrations in the medulla oblongata were observed in the A2 region and the nucleus commissuralis, which contained at least twice as much noradrenaline as did the more rostral part of the nucleus tractus solitarii.

Adrenergic and cholinergic stimulation of 32P-labeling of phospholipids in rabbit iris muscle

The phospholipid and cholesterol composition of the iris muscle of the rabbit was determined, and the incorporation of 32Pi into the individual phospholipids of irises incubated in Krebs Ringer bicarbonate buffer that contained glucose in the presence or absence of adrenergic or cholinergic neurotransmitters and their agonists and antagonists was investigated. The results of studies on the characteristics and the effects of norepinephrine and other neuropharmacological agents on the 32P-la-beling of phosphatidic acid (PhA). phosphatidylinositol (PhI), phosphatidylcholine (PhC). phosphatidyl-ethanolamine (PhE) and phosphatidylserine (PhS) in the iris muscle are reported. Addition of l-nore-pinephrine. l-epinephrine, dopamine or acetylcholine (0.003 to 0.3 mM) to irises which were preincubated for 20 min in 32P-Krebs-Ringer without cold phosphate stimulated significantly the isotope incorporation into PhA and Phi. but not PhC. In contrast histamine, noremetanephrine. metanephnnc. adrenochrome. 6-hydroxydopamine and eserine (0.003 to 0.3 mM) had a negligible effect on the isotope incorporation. At higher concentrations of norepinephrine (10mM), labeling of PhA, PhI and PhC was elevated to 989. 630 and 185 per cent of that of the control respectively. It was concluded that in the iris muscle α-receptors and not β-receptors are involved in the stimulatory action of norepinephrine on 32Pi incorporation into phospholipids. This conclusion is based on the following findings. (a) Only α-stimulators. such as norepinephrine and phenylephrine. increased significantly the labeling of PhA and PhI. This effect was blocked by the α-blockers. phenoxybenzamine and phentolamine. (b) Isoproterenol, a β-stimulator, had no effect on the labeling of PhA and PhI. Sotalol and propranolol, both β-blockers, did not block the norepinephrine stimulation of 32Pi incorporation, (c) Cyclic AMP (or dibutyryl cyclic AMP), which has been suggested as a β-receptor mediator, exerted no influence on the phospholipid effect. Atropine blocked completely the acetylcholine-stimulated 32P-labeling of PhA and PhI. At 0.3 mM, phentolamine and propranolol increased by several-fold the isotope labeling of PhA, PhI and, unexpectedly, of CDP-diglyceride and inhibited that of PhC. The properties of the norepinephrine stimulation of 32P-labeling in the iris muscle can be summarized as follows, (a) It is concentration dependent; but this dependence varies with the condition of incubation, (b) It is temperature dependent, but the effect is lost upon freezing and thawing, (c) It can be demonstrated during a period of 3 days of aging at 4. (d) Glucose is required for maximal stimulation, (e) The phospholipid effect is not specific to a particular subcellular fraction, (f) Addition of norepinephrine brought about a 25 per cent decrease in the level of PhI and a 63 per cent increase in the level of PhA. (g) Time-course studies on the 32P-labeling of phospholipids in the presence and absence of norepinephrine revealed that, in contrast to PhI and PhC, the specific radioactivity of PhA increased with time of incubation (0.90 min) only when the neurotransmitter was added, (h) Direct activation of the enzyme diglyceride kinase by norepinephrine does not appear to be the molecular mechanism underlying the phospholipid effect. Our data suggest that in the iris muscle norepinephrine increases the turnover of PhA and PhI phosphorus by stimulating the hydrolysis of endogenous PhA or PhI. or both, to form more membraneous diglyceride. The latter is then rephosphorylated by diglyceride kinase to form more labeled PhA.

Postsynthetic stabilized modification of adenylate cyclase by metabolites.

Membrane preparations of adenylate cyclase of cat cerebral particles (Klainer et al., 1962) and those of rat cerebral-cortex particles (Drummond et al., 1971) have been reported to be susceptible to stimulation by adrenaline. However, considerable variations in the efforts of catecholamines were also reported (Klainer et al., 1962). This suggested the possibility that environmental effects were producing stabilized modifications of adenylate cyclase with the potential to alter the normal thresholds of adenylate cyclase response to hormones. Particulate preparations of adenylate cyclase from rat brain cerebral cortex were obtained from male Sprague-Dawley rats (weighing about 300g) which were stunned and decapitated at 4°C. Mgz++-treated particles were prepared as follows: the cerebral cortex of each brain was sliced and collected under the cover of 3 ml of a 2 m ~ Tricine*Tris-1 mM-MgSO, buffer, pH7.4. The tissue was weighed and then homogenized in a glass motor-driven homogenizer at low speed for 2min. The homogenates were centrifuged in a cold-room (4°C) at 1700revJmin for 20min in head 809 of a CL International centrifuge. The pellet was washed twice and finally suspended in 3 ml of the same homogenizing medium and stored at -70°C. After thawing for 1 h at room temperature, portions of the particulate preparations were incubated under the conditions described under Fig. 1 for the assay of their adenylate cyclase activity. The cyclic AMP formed by adenylate cyclase was measured by the Gilman (1970) method with the use of the saturation assay procedure of Brown et al. (1972). Fig. 1 shows theeffect of noradrenaline on the activity of adenylatecyclaseon theMgZ+treated particles. Noradrenaline-dependent stimulation of adenylate cyclase was maximal in the range 0.025-0.25 m~ substrate concentrations. The data were replotted in terms of the Hill equation and the concentration of ATP for half-maximal velocity (K,,,) was found to decrease from 0 . 2 m ~ , in the absence of noradrenaline, to 0 . 0 7 m ~ in the presence of 1 mwnoradrenaline. Hence, catecholamines in high concentration exert a modifying force on the membrane that changes adenylate cyclase from a high-K,,, form to a low-K,,, form. On the other hand, high concentrations of noradrenaline are found in the urine of acute psychotic patients (Bunney, 1968), which appears to indicate that under pathophysiological stress the adrenals or the central nervous system may respectively allow for the persistence for long periods of time of increased amounts of catecholamines in the blood or in the synapse. It has been proposed (Bennum, 1974a) that high concentrations of catecholamines persisting for long periods of time would cause disruption of the chelated structures which allow the activation and regulation of enzymes within a membrane (Bennun, 1971, 19746). Studies on the stability of adenylate cylase should therefore indicate whether the properties of the enzyme can be altered by its prolonged exposure to hormones and/or metabolites. In order to discover if stabilized conformations could be obtained experimentally, adenylate cylase preparations were pre-incubated under the conditions described in Table 1. The specific activities without noradrenaline are reported in percentage of the preincubated control as noradrenalineindependent activity, which indicates inactivating or activating effects. The noradrenaline-dependent effect, indicating sensitivity to the hormone, was calculated by expressing activity with 1 m-noradrenaline as a percentage of that in its absence. Table 1 shows that preincubation of Mp3+-treated particles with ATP-Mgactivated the adenylate cyclase, but also desensitized the enzyme to its stimulation by noradrenaline. Preincubation with noradrenalinein activated the enzyme. However, if noradrenaline and ATP-Mg were jointly present during preincubation, only a 10% decrease in noradrena-

Muscle load and constriction of the rabbit ear artery.

This isolated, perfused ear artery of the rabbit has been used to examine the effect of alterations in muscle load on the construction of arteries. The equilibrium muscle load, taken as the difference in wall stress between the relaxed and constricted artery at the same external radius, was varied by changing the transmural pressure and by constricting the artery. 2. The equilibrium muscle load increased initially and then declined with decreasing external radius when the transmural pressure was kept constant. The maximum muscle load was reached when the relaxed external radius had been reduced by 11% at 80 mmHg and by 4-5% (relative to the radius at 80 mmHg) at 160 mmHg. 3. Arteries from young rabbits (3-6 months in age) which were partially constricted by adrenaline or spontaneous activity responded better to 60 sec of 4 Hz field stimulation at transmural pressures above 100 mmHg than did relaxed arteries. Neither field stimulation nor high concentrations of noradrenaline ( is greater than 800 ng/ml.) were able to constrict most arteries effectively at pressures above 160-170 mmHg unless partial constriction was present. The partial constriction reduced the load placed on the muscle by the same transmural pressure. Constrictio n during field stimulation was due largely to the release of neurotransmitter. 4. Ear arteries from young and older rabbits differed little in their ability to constrict against different transmural pressures. The one major difference was a lesser maximum constriction of arteries from older rabbits (18-24 months in age). However, arteries from older rabbits constricted well at the higher transmural pressures only because wall thickening largely compensated for a decreased ability of the muscle to develop active tension. 5. It is concluded that a decrease in internal radius to wall thickness ratio by either sufficient partial vasoconstriction or by wall thickening favours constriction of arteries because the load placed on the muscle by the same transmural pressure is reduced. Wall thickening may be an important compensatory reaction for deteriorating muscle contraction.

Indomethacin and the role of prostaglandins in adipose tissue

Indomethacin (2 or 10 μg/ml) or meclofenamic acid (4 μg/ml), two potent inhibitors of prostaglandin biosynthesis, did not affect basal or noradrenaline (10 −6 M) stimulated lipolysis when added to isolated rat fat cells. Indomethacin (5 μg/ml blood) similarly was without effect on blood flow, on lipolysis or on 3H-noradrenaline overflow before, during and after nerve stimulation (4 Hz) in perfused canine subcutaneous adipose tissue in situ. Indomethacin given to rats 5 × 5 mg/kg at 10–14 hr intervals p.o. had no effect on arterial glycerol concentration, but caused a significant hypoglycemia. Fat cells or fat pads extracted from such rats had an unchanged basal lipolytic rate but a lowered responsiveness to high concentrations of noradrenaline (4 × 10 −7-2 × 10 −6 M), compared with controls. However, 10 −7 M noradpresumbaly caused a higher lipolytic response in fat cells from indomethacin-treated rats than from controls, presumably because the former caused a smaller degradation of naradrenaline during the incubation period. Indomethacin (0·2–20 μg/ml) had no effect on cAMP binding to protein kinase, but apparently caused membrane stabilization, since erythrocytes from indomethacin-treated rats were more resistant to hypotonic lysis than red cells from control animals. Our results suggest that indomethacin has a multitude of biological effects, some of which may be unrelated to inhibition of prostaglandin biosynthesis. When considered together with previous results the findings also suggest that endogenous prostaglandins are of minor importance as feed back inhibitors of lipolysis in adipose tissue.

Current spread in the smooth muscle of the rabbit aorta.

1. The electrical responses of the smooth muscle cells of the rabbit aorta to both extracellular and intracellular stimulation were studied using the partitioned chamber and Wheatstone bridge method.2. No spontaneous electrical activity was recorded when the tissue was soaked in either isotonic or hypertonic Krebs solutions, and strong depolarizing currents also failed to trigger action potentials in either solution.3. The circular muscle of the aorta has cable properties. Mean values in isotonic Krebs solution were 2.1 mm for space constant and 433 msec for time constant.4. The input resistance (mean 12 MOmega) measured with the Wheatstone bridge method was considerably smaller than that calculated from values measured with the partitioned chamber method.5. Electrotonic potentials could be recorded from the smooth muscle of ;injury bundles' although their amplitude was smaller than that from the intact bundle.6. High concentrations of noradrenaline readily induce oscillatory potentials from the aorta in both isotonic and hypertonic Krebs solutions. It was estimated by simultaneous recording with two micro-electrodes that noradrenaline-induced oscillatory potential can conduct in both longitudinal and transverse directions of the smooth muscle.7. These results suggest that the smooth muscle of the aorta behaves like a syncytium or single unit muscle and activation of cells on the inner surface of the media can be induced both by electrotonic current spread and by propagation of oscillatory potentials from the outer cells directly activated by the transmitter.

Norepinephrine and dopamine content of hypothalamic nuclei of the rat

The concentrations of norepinephrine and dopamine of 27 isolated rat hypothalamic nuclei or nuclear subdivisions have been determined using an enzymatic-isotopic assay. The hypothalamic nuclei contain 3–20 times more NE and DA than is measured in the cortex. They are distributed unevenly throughout the hypothalamus and individual hypothalamic nuclei are heterogenous as regards their content of the amines. The dopamine content of the median eminence is among the highest measured in the brain (65 ng/mg protein). The norepinephrine content is about half that of dopamine. All of the hypothalamic nuclei contain dopamine. It is highly concentrated in the rostral subdivisions of the arcuate nucleus, the paraventricular and dorsomedial nuclei, the retrochiasmatic area, the medial posterior subdivision of the ventromedial nucleus and in the medial forebrain bundle at the posterior hypothalamic level. The highest concentrations of norepinephrine were found in the paraventricular and dorsomedial nuclei and in the retrochiasmatic area. The rostal subdivision of the arcuate nucleus and the periventricular and preoptic suprachiasmatic nuclei are also rich in norepinephrine. The posterior hypothalamus (premammillary nuclei, caudal subdivision of the arcurate nucleus, posterior hypothalamic nucleus) contains norepinephrine and dopamine in relatively low concentrations.

Adrenergic mechanisms in cerebral blood vessels: effect of tyramine on the isolated middle cerebral artery of the goat.

Tyramine induces dose-dependent changes in tension of the isolated middle cerebral artery of the goat. Cocaine, phentolamine and reserpine reduce the sensitivity of the tissue to tyramine by factors of 2.8, 3.7 and 3.7, respectively. The norepinephrine (NE) concentration of the arteries of the circle of Willis is 2.10 µg per gram and the corresponding value for the right atria is 1.25 µ per gram. Reserpine pretreatment (0.02 mg/kg/day for three days) reduces the NE concentration of the cerebral arteries to undetectable levels and that of the right atria to 2.4% of the control value. The relatively high concentration of NE of the cerebral arteries of the goat suggests that this tissue receives considerable sympathetic innervation. It is likely that part of the contractile response to tyramine is due to release of endogenous NE from sympathetic stores in the artery. However, some contractile response to tyramine remains after α-adrenergic blockade, reserpine pretreatment and in the presence of cocaine, suggesting that in addition to an indirect action (release of NE) tyramine also possesses a direct stimulatory effect in cerebral arteries.

Noradrenaline uptake properties of the anococcygeus muscle of the rat.

Noradrenaline (NA) uptake was measured in the anococcygeus by two methods: quantitative fluorescence microscopy and radioactive tracer techniques. A pharmacological analysis of the contribution of adrenergic nerve, smooth muscle, and nonspecific binding to collagen and basement membrane was attempted by studying the effects of desmethylimipramine and phenoxybenzamine on uptake. The importance of metabolic degradation in the process of NA accumulation was estimated by examining the effect of the combined use of iproniazid to inhibit monoamine oxidase and of β-thujaplicin to inhibit catechol O-methyltransferase.The results suggest that NA accumulation in this tissue at concentrations below 2 × 10−6 g/ml was almost entirely due to uptake into adrenergic nerves and to nonspecific binding. At higher concentrations of NA, above 2 × 10−6 g/ml, uptake into the smooth muscle cells began to contribute increasingly to the total accumulation. Inhibition of the metabolic enzymes increased the fluorescence of smooth muscle incubated with high concentrations of NA, confirming that only at those high concentrations was there any intracellular accumulation of NA and suggesting that the NA taken up by these smooth muscle cells is normally almost completely metabolized. Incubation with the inhibitors of catecholamine metabolism, and also with phenoxybenzamine, reduced both the fluorescence in the adrenergic nerve terminals and the accumulation of tritiated compounds by the whole tissue. Possible explanations for this observation are discussed.In the radioactive experiments 14C-sorbitol was used to measure the extracellular space (ECS). The ECS appeared to be a two-compartment system, a large, fast-filling and a small, slow-filling compartment. Electron micrographs suggest a possible basis for these two compartments in the large spaces between muscle bundles and the very narrow clefts between the cells in individual bundles. Quantitative estimates of the magnitude of these two spaces from electron micrographs are not incompatible with this.

On the reversal by (+) and (-)-propranolol of irreversible α-adrenoceptor blockade in rabbit aorta

Summary (+)- and (−)-Propranolol were equally effective in producing an apparent reversal of α-adrenoceptor blockade produced by a number of irreversible α-adrenoceptor antagonists in rabbit aortic strips: MJ 1999 was ineffective. Propranolol also partly relieved the apparent desensitization produced by high concentrations of norepinephrine. These results indicate that β-antagonist reversal of irreversible α-adrenoceptor antagonism is not attributable to a shift in the relative availability of α- and β-adrenoceptors or to displacement of antagonist from the α-adrenoceptor.

Biochemical monitoring of multiple injury patients.

Abstract Forty-five consecutive patients with multiple injuries were studied at the emergency department and intensive care unit of an accident hospital. The series was divided into two groups, one consisting of 16 patients whose total trauma was classified as severe (nine deaths) and one comprising 29 patients with a moderate total trauma (no mortality). Plasma catecholamines, arterial lactate, serum creatinine and blood urea nitrogen were systematically determined 0–2, 6, 12 and 24 h and 2, 4 and 8 days after the accident. A transient increase in plasma adrenaline was seen, which correlated with the severity of the injuries and the blood loss. A persistently high concentration of plasma noradrenaline was noted in the group with severe injuries indicating prolonged sympathetic over-activity. During the first week after the trauma this group had high lactate and creatinine concentrations, and in the moderately injured group the values exceeded the normal range only initially. We conclude that the biochemical pattern observed constitutes evidence of a severe overall trauma and is useful in grading injuries and evaluating prognosis.

Effect of propranolol and controlled cardiac output on acute tolerance to noradrenaline

The effects of propranolol and controlled blood flow on the acute tolerance which develops to the pressor response to noradrenaline infusions was studied in the anaesthetized open-chest dog, both intact and during left heart bypass, and in the perfused forelimb. The acute tolerance which develops to noradrenaline infusion is characterized by an early and a late phase. The early phase of tolerance observed during infusion of low noradrenaline concentrations was due to a decrease in vascular resistance in the anaesthetized dog and in the perfused forelimb. Since the early phase of tolerance was not observed after treatment with propranolol, it is suggested that vascular β-adrenoreceptors are involved in the phenomena of tolerance. The early phase of tolerance is abolished and the late phase diminished during infusion of high concentrations of noradrenaline when blood flow is maintained constant with a pump although venous return decreased. It is concluded that changes in the cardiac output are important in the development of acute tolerance to the pressor effect of noradrenaline in the dog.

Undesirable Prepubertal Effects of Levodopa

To the Editor.— Histochemical studies indicate that dopamine is the primary amine in the median eminence. It is located in close contact to the capillaries of the pituitary portal system. 1 The hypothalamus contains high concentrations of norepinephrine. Recent observations on human subjects report that the oral administration of levodopa practically shuts off prolactin secretion 2,3 but raises growth hormone 4 and follicle-stimulating hormone levels in the blood for a period of four to six hours after each dose. 4,5 This probably results from stimulation of the hypothalamus to secrete inhibiting and releasing factors. 6,7 The following observation is probably interesting in two respects—first, because of the clinical effects of prolonged levodopa administration; second, because of the low dose in which orally given levodopa may be active in children. In 1971 a 12-year-old boy weighing 35 kg was observed because of psychomotor epilepsy and behavior disturbances that persisted after suppression

Concentrations of calcitonin and catecholamines in pheochromocytomas, a mucosal neuroma and medullary thyroid carcinoma.

Two patients with the medullary thyroid carcinoma syndrome were studied; one had multiple mucosal neuromas and ganglioneuromatosis, the other had bilateral pheochromocytomas. Both biological and immunological assays of a mucosal neuroma revealed high concentrations of calcitonin (CT) in the tissue (170 and 130 MRC U/g by the two assay methods, respectively). There was no microscopic evidence for contamination of the neuroma by medullary carcinoma. The two pheochromocytomas from the other case contained 6.2 and 13 MRC U of CT/g by immunoassay and measurable amounts by biological assay although, in the bioassay, there was partial inhibition of the hypocalcemic response of the assay rats by the high concentrations of epinephrine (840–960 ng/mg) and norepinephrine (215–480 ng/mg) in the unfractionated extracts. This interference was eliminated by separation of CT from catecholamines by gel nitration. No metastatic medullary carcinoma was found in the pheochromocytomas. In the patient with bilateral pheochromocytomas, metastatic (liver) medullary thyroid carcinoma contained levels of epinephrine (30 ng/mg) and norepinephrine (11 ng/mg) which were high but only about 1/30th those measured in the benign pheochromocytomas. We conclude that pheochromocytomas and mucosal neuromas can, on occasion, produce CT, and furthermore that some medullary thyroid carcinomas can probably produce epinephrine and norepinephrine in addition to CT.

Cyclic 3'5'-adenosine monophosphate in isolated bone cells. Response to low concentrations of parathyroid hormone.

Treatment with purified bovine PTH (2000 U/mg) in vitro increased the cyclic- 3’5’AMP content of isolated bone cells dispersed from rat calvaria and maintained in monolayer culture. Theophylline (1-5 HIM) markedly potentiated the action of PTH. In the presence of theophylline, PTH (1 M-g/ml) raised bone cell cyclic-3’S’AMP 14-fold in 30 sec and 30-fold in ISO sec. Low concentrations of PTH (10-100 ng/ml) were moderately effective (2-4-fold increases) and a physiological concentration (1 ng/ ml) gave a small ( + 25%) but statistically significant increase. A synthetic N-terminal peptide fragment (amino acids 1-34) of PTH was 50% as active as native hormone, whereas a synthetic 2-34 fragment was virtually inactive. Cyclic-3’5’ AMP increased slightly upon exposure to high concentrations of thyrocalcitonin, epinephrine, norepinephrine, or lysine vasopressin, but was not affected by adrenocorticotropin or insulin. Repeated subculturing caused a progressive decline in the sensitivity of bone cells to PTH. Isola...

Factors affecting the extraneuronal inactivation of noradrenaline in cardiac and smooth muscle.

1. The relation between density of adrenergic innervation, noradrenaline (NA) accumulation (as seen with the fluorescence histochemical method) in tissues incubated in a high concentration of NA, and monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) activities, were examined in a wide range of tissues from different species.2. Evidence was obtained to support the proposal that accumulation of NA in the non-innervated smooth muscle of the human umbilical artery and chick amnion is associated with very low activities of COMT within muscle cells.3. The wide variation in tissue accumulation of NA in adrenergically innervated muscles was confirmed. For example, in the rabbit atrium and rat vas deferens, there was high NA accumulation in vascular smooth muscle but not in other muscle cells. In the mouse vas deferens there appeared to be preferential NA accumulation in the outer longitudinal muscle in comparison with the circular muscle. In the ventricle of the rat and mouse individual muscle cells showed different degrees of accumulation of NA. Many unidentified fluorescent cells were revealed in the submucosa of the guinea-pig ureter following loading with NA. The highest activities of COMT were found in the rat vas deferens and the lowest in the rabbit vascular tissues; the highest activity of MAO was found in the guinea-pig ileum, and the lowest in the rat aorta.4. No simple relation between tissue activities of MAO and COMT and degree of NA accumulation was found. Possible directions for further investigation of the problem are discussed.

α-Adrenoceptors of aortae from genetically hypertensive rats: reaction with 2-halogenoethylamines

Abstract The responses of aortic rings from adult spontaneously hypertensive and Carworth normotensive Wistar rats to noradrenaline were compared. The former developed slightly more tension at low, and markedly less tension at high concentrations (> 10−8m) of noradrenaline. The α-adrenoceptors of these tissues were probed using 2-halogenoethylamines to compare quantitatively α-adrenoceptors in normotensive and hypertensive tissue. The kinetics of the recovery of response to noradrenaline from the short-lived antagonism produced by NN-dimethyl-2-bromo-2-phenylethylamine were identical in aortae from both strains of rat. The rate of recovery of response was the same as the rate of loss of tritium from the tissues, suggesting the absence of spare receptors in rat aorta. An estimation of the number of α-adrenoceptors in aortic tissue did not show a difference between normotensive and hypertensive tissues. Evidence is presented that 2-halogenoethylamines react at two kinetically distinguishable sites in rat aorta. The rates of return of response to noradrenaline after receptor blockade with N-(2-bromoethyl)-N-ethyl-N-1-naphthylmethylamine (SY-28) in tissues pretreated with NN-dimethyl-2-bromo-2-phenylethylamine were the same in aortic smooth muscle from both strains of rat. No significant difference was found in the reactions of 2-halogenoethylamine α-adrenoceptor antagonists in aortic tissue from either strain of rat.

Differences of cardiac reactivity between spontaneously hypertensive and normotensive rats

The reactivity of the isolated atria of spontaneously hypertensive rats (SHR) in hypertensive and pre-hypertensive state (30–35 days after birth) was compared to those of two control groups of normotensive Wistar rats (NWR). SHR atria, but not pre-hypertensive atria, showed a greater amount of spontaneously developed tension than NWR atria, which may reflect compensatory changes due to the high peripheral vascular resistance in SHR. The inotropic and chronotropic responses of SHR and pre-hypertensive atria to isoproterenol were less than those of NWR atria. In SHR atria (hypertensive and pre-hypertensive), a high concentration of epinephrine and norepinephrine elicited a decreased inotropic effect in comparison to the NWR response. An abnormal negative inotropic response to potassium was observed in SHR atria (both hypertensive and pre-hypertensive). These results may indicate a difference in the nature of the β-receptor of SHR and NWR atria and an intrinsic, contractile abnormality of SHR atria. The low reactivity of SHR atria to the β-receptor stimulant may be attributed to the original changes in musculature rather than secondary changes resulting from compensatory mechanisms of hypertension.

Catecholamines in turkeys with high or low blood pressure: effects of tyrosine hydroxylase inhibitor and ganglionic blocker.

Following six generations of genetic selection for hyper- or hypotensive turkeys, tissues were assayed for catecholamines. The concentrations of norepinephrine and epinephrine were essentially the same in both groups except for the posterior aorta and the left ventricle. The latter tissues showed higher concentration of norepinephrine in the hypertensive birds.The administration of α-methyl-L-tyrosine or mecamylamine reduced norepinephrine to a greater extent in hyper- than in hypotensive turkeys. The results suggest that hypertension may be caused by increased rate of norepinephrine release.

Effects of postulated neurochumoral transmitters on the isolated radula protractor of Busycon canaliculatum

1. 1. Acetylcholine potentiates twitches in low concentrations and induces contracture in high concentrations. Acetylcholine contracture is temperature dependent. 2. 2. Tryptamine is more effective than 5-hydroxytryptamine in potentiating twitches and in inducing rhythmicity. 3. 3. High concentrations of noradrenaline, tyramine and GABA potentiate twitches. 4. 4. High concentrations of adrenaline, dopamine and glutamic acid depress twitches. 5. 5. At comparable concentrations, tryptamine is more effective than 5-hydroxytryptamine in relaxing acetylcholine contracture.