Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DbetaH-saporin.
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Phenylethanolamine-N-methyltransferase (PNMT)-containing neurons in the rostral ventrolateral medulla (RVLM) are believed to play a role in cardiovascular regulation. To determine whether injection of anti-dopamine beta-hydroxylase (DbetaH)-saporin directly into the RVLM in rats could selectively destroy these cells and thereby provide an approach for evaluating their role in cardiovascular regulation, we studied rats 2 wk after unilateral injection of 21 ng anti-DbetaH-saporin into the RVLM. There was an approximately 90% reduction in the number of PNMT-positive neurons in the RVLM, although the number of non-C1, spinally projecting barosensitive neurons of this area was not altered. The A5 cell group was the only other population of DbetaH-containing cells that was significantly depleted. The depressor response evoked by injection of tyramine into the RVLM was abolished by prior injection of toxin. The pressor response evoked by injection of glutamate into the RVLM was attenuated ipsilateral to the toxin injection but was potentiated contralateral to the toxin injection. Thus anti-DbetaH-saporin can be used to make selective lesions of PNMT-containing cells, allowing for the evaluation of their role in cardiovascular regulation. (+info)
Low-level exercise echocardiography detects contractile reserve and predicts reversible dysfunction after acute myocardial infarction: comparison with low-dose dobutamine echocardiography.
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OBJECTIVES: The aim of this study was to evaluate low-level exercise echocardiography (LLEE) in detecting contractile reserve and predicting functional improvement of akinetic myocardium early after acute myocardial infarction (AMI). BACKGROUND: Experimental and clinical studies have shown that low-dose dobutamine enhances contractile function of dyssynergic but viable myocardium in patients with recent AMI. We hypothesized that endogenous catecholamines produced during a LLEE test could serve as a myocardial stressor to elicit contractile reserve. METHODS: Fifty-two consecutive patients with first AMI and > or =2 akinetic segments in the infarct-related territory underwent 5 +/- 2 days after AMI low-dose dobutamine echocardiography (LDDE) (5, 10 and 15 microg/kg/min) and LLEE (25 W during 3 min on a supine bicycle, with continuous echocardiographic recording). Both tests were performed on the same day, in random order. Follow-up echocardiography was obtained one month later. Regional wall thickening was semi-quantitatively assessed using a 16-segment, 5-grade scale model. Contractile reserve was defined as improvement in wall thickening of > or =1 grade. RESULTS: Mean increase in heart rate during stress tests was 15 +/- 7 beats/min with LLEE and 13 +/- 6 beats/min with LDDE (p = NS). Contractile reserve was detected in 119 (55%) of 217 akinetic segments at LLEE and in 137 (63%) segments at LDDE. At follow-up study, functional improvement was identified in 139 (64%) segments. Sensitivity, specificity and positive and negative predictive values for predicting functional recovery were 81%, 92%, 95% and 73%, respectively, for LLEE, and 91%, 86%, 92% and 84%, respectively, for LDDE. Moreover, there was a good correlation between systolic wall thickening measured in the center of the dyssynergic area during stress tests and at follow-up study: r = 0.77, p < 0.001 with exercise testing and r = 0.73, p < 0.001 with dobutamine testing. CONCLUSIONS: Low-level exercise echocardiography provides a promising alternative to LDDE for identifying myocardial viability and predicting reversible dysfunction early after AMI. (+info)
Daily rhythm in rat pineal catecholamines.
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A daily rhythm in the oscillations of pineal dopamine, norepinephrine and epinephrine content was found in male Wistar: Han rats. The acrophases of the oscillations were localized in the first half of the dark period and generally higher values were found in the dark part of the day. (+info)
Aging, high salt intake, and renal dopaminergic activity in Fischer 344 rats.
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The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats. (+info)
Role of calcium channels in catecholamine secretion in the rat adrenal gland.
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1. We elucidated the contribution of voltage-dependent Ca2+ channels to cholinergic control of catecholamine secretion in the isolated perfused rat adrenal gland. 2. Nifedipine (0.3-3 microM) inhibited increases in noradrenaline output induced by transmural electrical stimulation (1-10 Hz) and acetylcholine (6-200 microM), whereas it only slightly inhibited the adrenaline output responses. Nifedipine also inhibited the catecholamine output response induced by 1, 1-dimethyl-4-phenyl-piperazinium (DMPP; 5-40 microM) but not by methacholine (10-300 microM). 3. omega-Conotoxin MVIIC (10-1000 nM) inhibited the catecholamine output responses induced by electrical stimulation but not by acetylcholine, DMPP and methacholine. 4. omega-Conotoxin GVIA (50-500 nM) had no inhibitory effect on the catecholamine output responses. 5. These results suggest that L-type Ca2+ channels are responsible for adrenal catecholamine secretion mediated by nicotinic receptors but not by muscarinic receptors, and that their contribution to noradrenaline secretion may be greater than that to adrenaline secretion. P/Q-type Ca2+ channels may control the secretion at a presynaptic site. (+info)
Nicotine infusion modulates immobilization stress-triggered induction of gene expression of rat catecholamine biosynthetic enzymes.
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The relationship between nicotine and stress is complex and paradoxical. Although people claim they smoke because it relaxes them, nicotine can trigger some of the effects observed with stress, including the release and synthesis of the catecholamines and their biosynthetic enzymes. This study examined one aspect of this confusing relationship between nicotine and stress. Multiple injections of nicotine bitartrate (5 mg/kg) elevated mRNA levels for the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase, and of preproneuropeptide Y in rat adrenal medulla more than did 1 mg/kg of nicotine bitartrate. In the locus ceruleus, substantia nigra, and ventral tegmental area both doses equally induced TH mRNA levels. Nicotine infusion (15 mg/kg/day) did not affect adrenal mRNA levels for any of the genes of interest and did not increase plasma corticosterone levels. However, in rats pre-exposed to nicotinic infusions, the response to a single immobilization (IMO) stress was markedly attenuated with respect to changes in adrenomedullary TH, DBH, and phenylethanolamine N-methyltransferase mRNA levels and in c-Fos protein levels. In the central nervous system, the chronic infusion of nicotine prevented the induction of TH mRNA by repeated IMO stress in the ventral tegmental area (but not in substantia nigra) and of DBH mRNA by single IMO in the locus ceruleus. These findings may explain some of the complex interactions between stress and exposure to nicotine. (+info)
Expression of HAND gene products may be sufficient for the differentiation of avian neural crest-derived cells into catecholaminergic neurons in culture.
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Members of the basic helix-loop-helix family of DNA binding proteins have important roles in the development of subpopulations of neural crest-derived neurons. We have cloned the chicken homologues of dHAND (HAND2) and eHAND (HAND1), basic helix-loop-helix DNA binding proteins whose neuronal expression is restricted to sympathetic and enteric neural crest-derived ganglia. Transcripts encoding dHAND and eHAND are expressed in sympathetic ganglia beginning at Hamburger and Hamilton stage 17-18. Antisense blockade of transcripts encoding HAND genes in neural crest-derived cells in vitro results in a significant reduction in neurogenesis. Differentiation of catecholaminergic neurons is also reduced by 52% if the expression of transcripts encoding dHAND and eHAND is reduced using antisense oligonucleotide blockade. The effect on neurogenesis and phenotypic expression of neural crest-derived neurons is specific; blockade of HAND gene expression has no apparent influence on the differentiation in vitro of neural tube-derived neurons. Use of a replication-competent avian retrovirus to constitutively express HAND genes in neural crest-derived cells in vitro, under nonpermissive growth conditions in medium supplemented with 2% chick embryo extract (CEE), induced precocious catecholaminergic differentiation. Constitutive expression of HAND gene products resulted in a significant increase in catecholaminergic differentiation of cells grown in medium supplemented with 10% CEE, a permissive growth condition for catecholaminergic development. These results suggest that the expression by neural crest cells of dHAND and eHAND may be both sufficient and necessary for catecholaminergic phenotypic expression. (+info)
Cocaine addiction: clues from Drosophila on drugs.
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Recent studies have shown that the fruitfly Drosophila exhibits behavioral sensitization in response to repeated exposure to cocaine; the exploitation of this genetically tractable model system for studying cocaine addiction is already providing new clues that may help understand the process of drug addiction in man. (+info)