In vivo biosynthesis of two subunit forms of dopamine beta-hydroxylase in rat brain.
(17/22)
In vivo biosynthesis of the 2 subunit forms of dopamine beta-hydroxylase (DBH) was examined in the rat brain. 35S-methionine was injected into the noradrenergic neurons of the locus coeruleus (LC) using a stereotactic device. Several hours later, newly synthesized 35S-Met-labeled DBH was immunoprecipitated and quantitated. Both Mr = 77,000 (77K) and 73,000 (73K) subunit forms were present in near-equal proportions after 4 hr of labeling, and these were indistinguishable from those isolated from rat PC12 pheochromocytoma cells by electrophoretic mobility. Both forms sedimented with the vesicular subcellular fraction of LC homogenates, and a portion of the 73K form could be released by hypotonic lysis of these vesicles. The 77K form predominated in the first 30 min labeling period, while the 73K form appeared more slowly over the next several hours. By 16 hr, the 73K form comprised about 2/3 of the total 35S-Met-labeled DBH present. Inhibition of protein synthesis with puromycin 30 min after 35S-Met injection into the LC did not prevent the subsequent appearance of the 73K form, suggesting that this subunit form was the product of posttranslational modification of the 77K subunit form in a fashion similar to that seen in PC12 cells. Also, newly synthesized 35S-Met-labeled DBH that underwent axonal transport from the LC to the anterior hypothalamus was predominantly the 73K subunit form. A single injection of the catecholamine-depleting drug reserpine (10 mg/kg, i.p.) produced a 17-fold increase in the relative synthesis of DBH 2 d later without affecting the proportion of its 2 subunit forms. (+info)
Antidiuretic effects of morphine microinjected into the hypothalamic supraoptic and paraventricular nuclei in a water-loaded and ethanol-anesthetized rat.
(18/22)
Effects of morphine microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, which contain neurons producing and releasing antidiuretic hormone (vasopressin), on the outflow and the osmotic pressure of urine and other visceral functions were investigated in a rat which was loaded with water and anesthetized with ethanol. The opioid drug, having predominantly mu-agonist activity, when microinjected into the SON or PVN induced potent antidiuretic effects in dose-dependent and time-dependent manners with no significant effects on the other visceral functions. The approx. ED50 values for morphine were 19 and 9 nmol when it was microinjected into the SON and PVN, respectively. The antidiuretic effects showed slow onset and long duration, with a minimal outflow at approx. 50 min after microinjection and a return to approx. 50% of the initial control value by 1.5 hr. The morphine-induced effects were inhibited by pretreatment with naloxone or atropine, but not inhibited by pretreatment with alpha- or beta-adrenoceptor antagonists, suggesting that the antidiuretic effects were mediated through an opioid receptor having low sensitivity to naloxone and also possibly mediated through a muscarinic receptor which was stimulated probably by the ACh released by morphine. (+info)
Cryoblockade of the ventromedial frontal cortex reverses hypertension in the rat.
(19/22)
The anteroventral part of the hypothalamus adjacent to the third ventricle (AV3V) has been implicated in electrolytic lesion studies as a site crucial to the development and maintenance of hypertension. Cryoblockade is known to alter synaptic and axonal transmission differently at different temperatures. In this study, cooling of the hypothalamus, including the AV3V area, to the temperature known to block only synaptic function did not alter blood pressure in two different models of experimental hypertension in the rat. Cooling sufficient to block both synaptic and axonal transmission, however, reduced blood pressure elevations to near normotensive levels. Synaptic cryoblockade in the ventromedial portion of the frontal cortex lowered experimental hypertension by 21 +/- 3 mm Hg (p less than 0.05). In normotensive controls, blood pressure was not altered by cryoblockade in either the frontal cortex or hypothalamus. Anatomical evidence provided by others shows that cells in the ventromedial frontal cortex project, in part, through the AV3V region to the brainstem cardioregulatory structures. These results indicate that neural activity arising in frontal cortex is axonally projected through the hypothalamus to maintain elevated blood pressure in experimental hypertension. (+info)
Evidence that cyclic nucleotides are not mediators of fever in rabbits.
(20/22)
The N6-2'-O-dibutyryl derivative of adenosine 3',5'-monophosphate (db cyclic AMP) and related compounds have been micro-injected into the preoptic/anterior hypothalamic nuclei (PO/AH) of the unanaesthetized, restrained rabbit and the effects on deep body temperature observed. Db cyclic AMP (100-400 micrograms) produced hypothermia of rapid onset in rabbits at an ambient temperature of 20-23 degrees C. Hypothermia was also produced by N2-2'-O-dibutyryl guanosine 3',5'-monophosphate (db cyclic GMP), but not by saline, sodium n-butyrate, adenosine 3',5'-monophosphate (cyclic AMP), guanosine 3',5'-monophosphate, adenosine 5'-mono-, di- or triphosphate. The initial hypothermic response to db cyclic AMP and db cyclic GMP was followed by a sustained rise in temperature. However, all compounds injected into the PO/AH produced a similar hyperthermia which was attenuated by paracetamol. Development of this tissue-damage fever abolished the hypothermic response to db cyclic AMP in some rabbits. The effects of db cyclic AMP on body temperature and behaviour were not reproduced by the adenylate cyclase activators, cholera toxin (0.125-5 micrograms) and guanyl imidodiphosphate (5-400 micrograms). It is concluded that hypothermia is the principal effect of db cyclic AMP on body temperature when injected into the PO/AH in rabbits. These data do not support the proposal that endogenous cyclic AMP in the rabbit brain mediates pyrexia. (+info)
Acute hypertension increases norepinephrine release in the anterior hypothalamic area.
(21/22)
Neurons in the anterior hypothalamic area play an important role in NaCl-sensitive hypertension in spontaneously hypertensive rats, and previous studies have suggested that baroreceptor feedback modifies the activity of these neurons. To test the hypothesis that the release of norepinephrine in the anterior hypothalamic area is modified by arterial baroreceptor reflex feedback and that this reflex release is disturbed in spontaneously hypertensive rats on a high NaCl diet, we used the push-pull technique to measure the release of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol in the anterior hypothalamic area. Seven-week-old male spontaneously hypertensive and normotensive Wistar-Kyoto rats were placed on a high (8%) or a basal (1%) NaCl diet for 2 weeks. The high NaCl diet elevated mean arterial pressure and greatly reduced basal norepinephrine metabolite levels in the anterior hypothalamic area of the spontaneously hypertensive (but not the control) rats (305 +/- 32 pg/10 min in the rats consuming 1% NaCl and 93 +/- 9 pg/10 min in the rats consuming 8% NaCl). An infusion of tramazoline (an imidizoline that causes long-lasting hypertension) that increased arterial pressure by 25 mm Hg elevated anterior hypothalamic area norepinephrine metabolite concentrations significantly more in the spontaneously hypertensive rats on the 1% NaCl diet (to 392 +/- 46 pg/10 min) than in those on the 8% NaCl diet (to 113 +/- 18 pg/10 min). In contrast, in Wistar-Kyoto rats the tramazoline-induced increase in arterial pressure elevated anterior hypothalamic area norepinephrine metabolite concentrations slightly more in rats on the 8% NaCl diet than in those on the 1% NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Chronic activation of brain areas by high-sodium diet in Dahl salt-sensitive rats.
(22/22)
To map changes in neuronal activity in the brains of Dahl salt-sensitive (Dahl S) vs. salt-resistant (Dahl R) rats by high-sodium diet, we used immunohistochemical detection of Fra-like proteins as a marker for long-term neuronal activation. Compared with Dahl R rats during regular sodium intake, Dahl S rats showed modestly higher expression of Fra-like immunoreactivity (Fra-LI) in the supraoptic nucleus, anterior hypothalamic area (AHA), central gray, and nucleus of solitary tract (NTS) at 5,6, and 9 wk of age but clearly elevated Fra-LI in the magnocellular part of the paraventricular nucleus (PVN) at 6 wk of age (but not at 5 and 9 wk). In the median preoptic nucleus (MnPO) Fra-LI was lower at 9 wk of age and no differences were observed in the parvocellular PVN and subfornical organ in Dahl S vs. Dahl R rats on regular sodium intake. Compared with Dahl S rats on a regular-sodium diet, Dahl S rats on a high-sodium diet from 4 to 9 wk of age had significantly increased blood pressure and experienced transient activation of magnocellular PVN and MnPO and virtually no changes in the activity of the parvocellular PVN, AHA, and NTS. In contrast, Dahl R rats showed marked activation in the magnocellular PVN after 1 and 2 wk on a high-sodium diet compared with Dahl R rats on a regular-sodium diet. The present study demonstrates that Dahl S rats show differential activation of brain areas participating in regulation of osmotic and cardiovascular homeostasis during development of sodium-sensitive hypertension. (+info)