Reduction In Noradrenaline Content Research Articles

Alpha 1- and alpha 2-adrenoceptors in rat cerebral cortex: effect of frontal lobotomy.

Surgical noradrenergic denervation of the cortex via frontal lobotomy was used to destroy the noradrenergic nerve endings and thus give some insight into the distribution of alpha-adrenoceptors. Frontal lobotomy caused a reduction in noradrenaline content in rat cerebral cortex (2.1 +/- 0.4 ng/mg protein for lesioned side, 6.0 +/- 0.3 mg/mg protein for non-lesioned side), indicating an effective noradrenergic denervation. The differences in 3H-clonidine and 3H-prazosin binding observed following surgery were a significant decrease in the number of alpha 2-adrenoreceptors (115.0 +/- 4.5 to 91.7 +/- 3.2 fmol/mg protein, n = 7, P less than 0.001) and a smaller but significant increase in the number of alpha 1-adrenoceptors (119.7 +/- 2.5 to 131.6 +/- 5.4 fmol/mg protein, n = 7, P less than 0.05) in the lesioned cortex. Results of this study indicate that alpha 2-adrenoceptors located on presynaptic noradrenergic terminals represent only a small proportion of the total alpha 2-adrenoceptors in rat cerebral cortex.

Effect of neonatal sympathectomy with 6-hydroxydopamine on reactivity of the renin-angiotensin system in spontaneously hypertensive rats.

1. Chemical sympathectomy was produced in spontaneously hypertensive rats by intraperitoneal injection of 6-hydroxydopamine hydrobromide (6-OHD) (100 μg/g body weight) on days 1, 4 and 7 of neonatal life and weekly thereafter until 6 weeks of age. The dose was then reduced to 50 μg/g body weight and injected every 2 weeks. 2. Studies were performed at 6 and 12 weeks of age in pentobarbital-anaesthetized rats. Plasma renin activity was measured before and 5 and 15 min after the administration of intravenous hydrallazine (5 mg/kg). Tissue noradrenaline concentration was determined in brains, hearts and kidneys from rats killed immediately upon completion of blood sampling. 3. The blood pressure of 6-OHD-treated rats was significantly lower than in untreated rats at 6 weeks (117 ± 3 and 146 ± 2 mmHg respectively) and 12 weeks (151 ± 5 and 196 ± 4 mmHg respectively). 4. Kidneys and hearts from 6-OHD-treated rats demonstrated a highly significant reduction in noradrenaline concentration at both 6 and 12 weeks; brain noradrenaline in treated rats was normal at 6 weeks and reduced only to 80% of normal at 12 weeks. 5. Control (pre-hydrallazine) plasma renin activity was significantly lower in 6-OHD-treated rats at 6 and 12 weeks. Nevertheless, renin release in response to intravenous hydrallazine, expressed in terms of absolute values of plasma renin activity, was not significantly different in the treated and untreated rats. When the percentage increase in plasma renin activity from control to 15 min post-hydrallazine samples was calculated, the response of the 6-OHD-treated rats was found to be significantly greater than the response in the untreated rats at each age. 6. These data show that treatment of neonatal rats with 6-OHD results in a significant reduction in basal activity of the renin-angiotensin system but does not interfere with the release of renin in response to hypotensive stress. In cases of severe compromise of adrenergic nervous system function, alternative mechanisms exist which allow the renin-angiotensin system to manifest a maximal response in order to maintain cardiovascular homeostasis.

Microfluorimetric scanning of sympathetic nerve fibers. An improved method to quantitate formaldehyde induced fluorescence of biogenic amines.

A two dimensional scanning procedure was developed for studying quantitative aspects of formaldehyde induced fluorescence (FIF) from noradrenaline containing nerve fibers. A computer (PDP 12) controlled scanning device was equipped with a cooled photomultiplier, a 0.5 micron scanning stage and a 0.5 micron measuring spot. Photodecomposition was reduced by a high scanspeed (100/sec) and a small excitation field. Digitized images were obtained with a high resolution. Data (10,000/scan) of large scan areas (2500 micron2) in the iris of the rat were transformed into fluorescence histograms, which allowed statistical evaluation. Visible changes induced in the histochemical preparation by administration of drugs (reserpine, L-Dopa) were reflected in characteristic changes in the histograms. A minor reduction in noradrenaline content, which was too small to be detected by visual observation of the microscopical image and by classical microfluorimetric methods, did evoke a significant change in the histograms. It is concluded that microfluorimetric scanning is a very sensitive technique for detecting changes of formaldehyde induced fluorescence from neuronal networks.

Effect of Lesions in the Ventral Noradrenergic Tract Produced by Microinjection of 6-Hydroxydopamine on Gonadotropin Release in the Rat1

Noradrenergic innervation to the hypothalamus is provided principally by the ventral noradrenergic tract (VNAT) which carries the axons of noradrenergic neurons whose cell bodies lie in the brain stem. To determine the importance of the VNAT in the stimulation of LH release induced by progesterone in ovariectomized, estrogen-primed rats, 6-hydroxydopamine (6-OHDA), an agent which selectively destroys catecholaninergic neurons, was microinjected bilaterally into this tract, 2 days after priming of the ovariectomized animals with 5 mug of estradiol benzoate, sc. Following microinjection, 2 mg of progesterone was injected sc to provoke LH release. A surge of FSH and LH release occurred 6 h after progesterone in control animals and those injected with the ascorbic acid diluent into the VNAT. Injections of 6-OHDA into the tract completely blocked both the LHP AND FSH surge. Control injections of 6-OHDA into the superior colliculus, the caudate-putamen or the frontal cortex did not alter the release of FSH and LH induced by progesterone. Twenty-four hours after injection of 6-OHDA into the VNAT, there was a slight reduction in norepinephrine content in the anterior hypothalamic area and a significant reduction in the region of the arcuate nucleus and median eminence. In this experiment, 6-OHDA injections into the VNAT blocked not only the FSH and LH release induced by progesterone but also the increase in serum prolactin which was present in control animals. In normal females, injections of 6-OHDA into the VNAT blocked the proestrous discharge of LH and partially blocked that of FSH. It is concluded that acute interruption of the VNAT induced by a 6-OHDA can block not only the stimulation of FSH and LH induced by progesterone, but also the preovulatory discharge of gonadotropins. The results suggest that increased impulse traffic in the VNAT on the afternoon of proestrus may be involved in induction of the proestrous gonadotropin surge.

The effects of repeated D-lysergic acid diethylamide injections on catecholamine levels and tyrosine hydroxylase activity in rat brain regions.

Abstract—Daily injections of 100 μg/kg of d‐lysergic acid diethylamide (LSD) for 14 days produced a significant decrease in the dopamine level in rat brain corpus striatum which was still apparent 15 days after the last LSD treatment. Further LSD injections did not change the amount of dopamine depletion. In cerebral cortex, 14 days of LSD injections produced a significant decrease in the norepinephrine level and a significant increase in tyrosine hydroxylase activity. The elevated tyrosine hydroxylase activity was still present 15 days after the final LSD injection but only in those animals receiving daily vehicle injections during this period. Pre‐treatment of rats with daily saline injections for 2 weeks before the 2 week period of LSD treatment prevented both the reduced norepinephrine content and elevated tyrosine hydroxylase activity usually found 24 h after the last LSD injection.

Endogenous brain norepinephrine levels following bilateral olfactory bulb ablation

Changes in endogenous norepinephrine (NE) levels after bilateral olfactory bulb section have been found to occur in the rat brain. Since olfactory tract projections are confined to the ventral adrenergic pathway, and this pathway projects to the pyriform cortex, it was decided to examine the distribution of endogenous NE between the pyriform cortex and the remaining neocortex. It was demonstrated that significant reductions in NE content occurred in both brain regions, although the greater reduction occurred in the pyriform cortex. There were no significant changes in hypothalamic NE. It is concluded that sensory deprivation plus olfactory system damage induce specific changes in central function, which relate to noradrenergic pathways.

Noradrenaline in the guinea pig alimentary canal: regional distribution and sensitivity to denervation and reserpine.

AbstractThe concentrations of noradrenaline, dopamine and 5‐hydroxytryptamine were studied in the stomach, duodenum, ileum, caecum (taenia coli), colon and rectum of the guinea pig. The wall of the alimentary canal was dissected into two fractions, one formed by the longitudinal muscle and myenteric plexus, the other formed by circular muscle, submucous plexus, submucosa and mucosa. In the longitudinal muscle‐myenteric plexus, the amount of noradrenaline was lower in the ileum (0.56 μg/g of fresh tissue), higher in the duodenum and caecum (0.75 μg/g and 0.82 μg/g respectively) and even higher in the stomach and rectum (0.85 μg/g and 0.91 μg/g). The highest value was found in the colon (1.33 μg/g), probably related to the occurrence of intramural adrenergic neurons.When extrinsic nerves to the ileum were damaged, the amount of noradrenaline in the corresponding ileal segment was reduced to less than 5 per cent within 3 days in both fractions of the wall. 6‐Hydroxydopamine (35 mg/kg intravenously) reduced to approx. one‐third the amount of noradrenaline in longitudinal muscle‐myenteric plexus of ileum and colon. Reserpine (1 mg/kg, subcutaneously injected 72 h‐earlier) reduced the amount of noradrenaline in the longitudinal muscle‐myenteric plexus of both ileum and colon to 0.01 μg/g. Doses of reserpine as small as 0.02 mg/kg were still effective in causing a great reduction in noradrenaline concentration. No difference in the effects on ileum and colon was observed.

Cardiovascular effects of 6-hydroxydopamine injected into a lateral brain ventricle of the rat.

6-Hydroxydopamine (6-OH-DA) was injected into the left lateral brain ventricle of normotensive, DOCA/NaCl or spontaneously hypertensive rats, and its effect on heart rate and blood pressure was studied. A single injection of 250 μg 6-OH-DA or 3 successive administrations of the same dose caused a reduction of noradrenaline content and tyrosine hydroxylase activity in several parts of the brain to 10–50% of the control values, indicating a considerable destruction of central adrenergic neurons. Heart rate and blood pressure decreased within 10 to 20 min after a single intraventricular injection of 6-OH-DA and both parameters returned to normal after 7 h. This effect was equally observed in normotensive and both types of hypertensive rats and regardless of whether the animals were conscious or anaesthetized. It was prevented by a prior intraventricular injection of phentolamine; this suggests that it is mediated by central alpha-adrenoceptors. The 6-OH-DA-induced bradycardia and hypotension were not influenced by a blockade of peripheral muscarinic receptors with scopolamine methylbromide; however, they were accompanied by a decrease of spontaneous discharges in the splanchnic nerve and, therefore, seem to be due to a reduction in peripheral sympathetic tone. The early cardiovascular effects of 6-OH-DA were sometimes followed by a second phase of bradycardia and hypotension. It occurred in normotensive rats 1–2 days after the second or third intraventricular injection of 6-OH-DA, and in spontaneously hypertensive rats already after a single injection. The hypotension of the second phase lasted 5–6 days, the bradycardia showed no recovery during the observation period which was limited to 3 weeks. Such long term cardiovascular effects of intraventricular 6-OH-DA were never observed in DOCA/NaCl hypertensive rats even after repeated administrations of the compound. The results provide evidence for the existence of a central adrenergic regulation of blood pressure and heart rate which seems to differ in normotensive and hypertensive rats.

Noradrenaline content of the heart of the adrenal-demedullated rat.

1. The noradrenaline (NA) concentration in the "heart" (atria and right ventricle) of male rats was estimated at different periods following adrenal demedullation. For 1-3 weeks after the operation there was, in all rats, a reduction in NA content of the tissue, whereas, after somewhat longer intervals, the concentrations had returned to normal in some but not in all animals, so that the range of values was very wide.2. In order to be able to test the effect of 2-aminotetralin on the cardiac NA of animals deprived of their medulla but having normal initial NA concentrations, an interval of 6-8 months was allowed to elapse between operation and injection of the drug; at this time the effect of the drug on cardiac NA was the same in intact and demedullated animals. There is thus no reason to attribute to the adrenal medulla any supporting role in the resynthesis of cardiac NA during periods of increased sympathetic activity.3. The time course of the pronounced fall in cardiac NA after adrenal demedullation resembles the time course of sodium retention shown by Gaunt, Renzi, Gisoldi & Howie (1967) to follow this operation. It is therefore suggested that it is the change in electrolyte metabolism which is responsible for the abnormality of NA storage; both phenomena occur in demedullated but not in adrenalectomized animals.

ADRENAL CATECHOLAMINES AND RELATED CHANGES DURING DIFFERENT PHASES OF MORPHINE ADMINISTRATION—A HISTOCHEMICAL STUDY

(1) Acute morphine treatment of rats reduced the total catecholamine content as well as the noradrenaline content of the adrenal gland. This was accompanied by increased ATPase activity and increased calcium content of the medullary cells. (2) After chronic morphine treatment, the total catecholamine content remained more or less unaltered, but the noradrenaline content was markedly increased together with the noradrenaline-containing areas, in comparison with what was observed in control animals. The ATPase activity of the medullary cells was found to be diminished along with the decreased calcium content. (3) In nalorphine-induced abstinence, a decrease in total catecholamine content together with a reduction of noradrenaline content and of noradrenaline-containing areas were observed. ATPase activity was also found to be increased with increased calcium content.

In utero immunosympathectomy of mice

The antibody for mouse submaxillary gland nerve growth-promoting protein crosses the placenta when injected into pregnant mice and produces a partial immunosympathectomy in the fetus. A dose schedule of 300 units/g twice a day during the 11th to 16th or 12th to 17th day of gestation resulted in significant decreases in the tissue norepinephrine content of the spleen, submaxillary glands and heart (15.5, 25 and 39 per cent, respectively, of control values). Nonrepinephrine levels in other tissues (lungs, gastro-intestinal tract, kidneys and uterus) were not significantly decreased. Injection of the antiserum once a day (300 units/g) during the 13th to 18th day of gestation resulted in a less pronounced reduction in norepinephrine content of the spleen and submaxillary glands. Exposure of the fetus to the antibody during the 7th to 12th day of gestation produced less marked decreases of norepinephrine levels in the spleen and the heart, but no siignificant changes in the norepinephrine content of the submaxillary glands. The latter results could indicate that during the earlier stages of development the postganglionic sympathetic neurones are too immature to be affected, that regeneration or repair takes place or that the antibody does not readily cross the placenta. Cell counts of superior cervical ganglia showed that prenatal antiserum treatment decreased the cell population by approximately 50 per cent. Catecholamine levels in the brain and the adrenal medulla were not affected by the prenatal treatment with the antiserum.