Differential effects of high salt intake on neuropeptide Y and adrenergic markers in hearts of Dahl rats

Adrenergic markers and neuropeptide Y (NPY) were examined in Dahl NaCl-sensitive and -resistant outbred male rats, fed either 0.35% or 8% NaCl diets for 8 weeks. The high salt diet caused left ventricular hypertrophy in sensitive rats but not in the resistant strain. Norepinephrine stores were not affected by high salt intake, but tyrosine hydroxylase, and dopamine beta-hydroxylase were elevated in the salt-induced hypertrophied left ventricle in conjunction with increased levels of nerve growth factor and p75 neurotrophin receptor. In contrast, high salt intake reduced ventricular neuropeptide Y in both Dahl salt-resistant and -sensitive rats.     

Adenosine mediates sustained adrenergic desensitization in the rat heart via activation of protein kinase C

Adenosine attenuates the myocardial metabolic and contractile responses induced by ss-adrenergic stimulation. Our study was conducted to investigate the longevity of this antiadrenergic action after adenosine exposure. Adenosine (33 micromol/L) was infused into isolated perfused rat hearts for 1, 5, 30, or 60 minutes, and the adrenergic responsiveness (AR) to isoproterenol (10(-8) mol/L) was determined at the end of each infusion period and during a 45-minute adenosine washout period. Interstitial levels of adenosine, as determined from epicardial surface transudates, returned to preinfusion levels within 10 minutes of washout. The duration of adenosine infusion had no effect on the extent of attenuation of AR at the end of the infusion. Whereas AR returned to preadenosine levels with washout of shorter adenosine infusions (1 and 5 minutes), there was a slow and incomplete recovery of AR after the longer exposures (30 and 60 minutes) to adenosine. The magnitude of this persistent antiadrenergic effect (PAE) of adenosine at 15 minutes of washout was proportional to the epicardial concentration of adenosine during infusion of the nucleoside. Infusion of adenosine either with the nonselective adenosine receptor antagonist 8-p-sulfophenyl theophylline or with the selective A1-receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine, abolished the PAE during the washout period. In addition, the PAE could be demonstrated only with the selective A1-receptor agonist 2-chloro-N6-cyclopentyladenosine and not with the selective A3-receptor agonist 4-aminobenzyl-5'-N methylcarboxamido-adenosine. When the protein kinase C (PKC) inhibitor chelerythrine was coadministered with adenosine, the PAE of adenosine was not apparent during adenosine washout. A 30-minute infusion of phenylephrine, an alpha-adrenergic agonist that enhances PKC activity, produced a PAE that lasted for up to 30 minutes of washout. This effect was prevented by the coinfusion of chelerythrine. Thus, it is concluded that the PAE of adenosine is determined by the myocardial concentration of this nucleoside and is manifested when myocardial concentrations of adenosine returned to baseline levels. Moreover, a 5-minute duration of adenosine exposure is required for the expression of the PAE. This latter effect seems to be dependent on adenosine-induced PKC activation via A1-receptors.     

Differential effects of a benzodiazepine on synaptic transmissions in rat hippocampal neurons in vitro

The effects of midazolam, one of the most popular benzodiazepines, on synaptic transmissions were compared with intracellular recordings between CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices. First, we studied the effects of midazolam on orthodromically evoked spikes, membrane properties and synaptic potentials. Secondly, the effects of a GABA(A) receptor agonist, muscimol, were examined on membrane properties to determine whether or not the densities of GABA(A) receptors are different between CA1-PCs and DG-GCs. Midazolam (75 microM) markedly depressed orthodromically evoked spikes in CA1-PCs, compared with those in DG-GCs. A GABA(A) receptor antagonist, bicuculline (10 microM), almost completely antagonized the depressant effects of midazolam on spike generation in CA1-PCs, whereas it had little effect on midazolam in dentate gyrus granule cells. Midazolam produced either depolarizing or hyperpolarizing effects on resting membrane potentials (Vm) with an input resistance decrease in CA1-PCs, whereas it produced depolarized Vm in DG-GCs. Midazolam significantly increased the amplitude of monosynaptic inhibitory postsynaptic potentials in CA1-PCs, whereas midazolam slightly decreased these in DG-GCs. Midazolam significantly decreased the amplitude of excitatory postsynaptic potentials both in CA1-PCs and DG-GCs. Muscimol (100 microM) produced either depolarizing or hyperpolarizing effects on Vm with an input resistance decrease in CA1-PCs, and it depolarized Vm with an input resistance decrease in DG-GCs. These results demonstrate that midazolam has differential effects on excitatory and inhibitory synaptic transmissions in hippocampal neurons. The mechanism of this difference could be partly due to the different types of GABA(A) receptors between CA1-PCs and DG-GCs.     

Differential distribution of alpha2A and alpha2C adrenergic receptor immunoreactivity in the rat spinal cord

alpha2-Adrenergic receptors (alpha2-ARs) mediate a number of physiological phenomena, including spinal analgesia. We have developed subtype-selective antisera against the C termini of the alpha2A-AR and alpha2C-AR to investigate the relative distribution and cellular source or sources of these receptor subtypes in the rat spinal cord. Immunoreactivity (IR) for both receptor subtypes was observed in the superficial layers of the dorsal horn of the spinal cord. Our results suggest that the primary localization of the alpha2A-AR in the rat spinal cord is on the terminals of capsaicin-sensitive, substance P (SP)-containing primary afferent fibers. In contrast, the majority of alpha2C-AR-IR was not of primary afferent origin, not strongly colocalized with SP-IR, and not sensitive to neonatal capsaicin treatment. Spinal alpha2C-AR-IR does not appear to colocalize with the neurokinin-1 receptor, nor is it localized on astrocytes, as evidenced by a lack of costaining with the glial marker GFAP. However, some colocalization was observed between alpha2C-AR-IR and enkephalin-IR, suggesting that the alpha2C-AR may be expressed by a subset of spinal interneurons. Interestingly, neither subtype was detected on descending noradrenergic terminals. These results indicate that the alpha2-AR subtypes investigated are likely expressed by different subpopulations of neurons and may therefore subserve different physiological functions in the spinal cord, with the alpha2A-AR being more likely to play a role in the modulation of nociceptive information.     

Comparative neurotoxic effects of root canal filling materials on rat sciatic nerve

The neurotoxic effects of the root canal filling materials--Endomethasone, N2 Universal, Traitement SPAD, Sealapex, and Calciobiotic Root Canal Sealer (CRCS)--were investigated on isolated rat sciatic nerves after local application. All of the canal filling materials reversibly inhibited the compound action potential (cAP) amplitudes. N2 Universal produced a 50% inhibition in 4.2 +/- 0.2 min. Traitement SPAD, Endomethasone, and CRCS produced the same inhibition in 6.4 +/- 0.3, 6.5 +/- 0.2, and 6.6 +/- 1.1 min, and Sealapex in 9.2 +/- 2.0 min. The inhibitory effect of Sealapex decreased fastest, and 43% recovery of cAP amplitude was observed in 60 to 70 min. The inhibitory effects of Endomethasone, CRCS, and N2 Universal were more pronounced, and 10 to 20% recovery in cAP amplitudes were observed in 2 h. The inhibitory effect of Traitement SPAD was more persistent with 4% recovery in 2.5 h.     

Acute effects of catecholamines on function of the rat right heart

OBJECTIVE: Although the haemodynamic effects of catecholamines on the rat left ventricle have been investigated extensively, only few systematic in vivo studies have been performed on the right ventricle. The aim was to examine the acute effects of noradrenaline and isoproterenol on rat right ventricular function. METHODS: Haemodynamic variables were measured during acute, 20 minute infusion of noradrenaline (0.1 mg.kg-1 x h-1) or isoproterenol (12 micrograms.kg-1 x h-1) in female Sprague Dawley rats. To estimate the contribution of alpha and beta receptor stimulation to these effects, eight rats each were infused with prazosin (0.1 mg.kg-1 x h-1), metoprolol (1.0 mg.kg-1 x h-1), or the alpha and beta antagonist carvedilol (0.5 and 1.0 mg.kg-1 x h-1) alone and in combination with noradrenaline or isoproterenol. RESULTS: Noradrenaline and isoproterenol increased right ventricular systolic pressure (RVSP) from 30.3 (SEM 0.5) (n = 32) to 72.7(2.7) (n = 24) and 72.3(4.4) (n = 8) mm Hg, right ventricular (RV) dP/dtmax from 1848(70.3) to 4058(301) and 3612(366) mm Hg.s-1, and heart rate from 329(6) to 371(6) and 420(8) beats.min-1, respectively. Metoprolol completely prevented the isoproterenol induced haemodynamic changes, but neither metoprolol nor prazosin was able to significantly affect the pressure effect of noradrenaline (noradrenaline + metoprolol: 67.3(6.9) mm Hg, noradrenaline + prazosin: 67.0(3.8) mm Hg). The combination of both blockers, however, prevented the noradrenaline induced rise in RVSP (noradrenaline + metoprolol + prazosin: 36.5(5.1), and noradrenaline + prazosin + metoprolol: 30.0(1.2) mm Hg). Carvedilol (1.0 mg.kg-1 x h-1) significantly attenuated the noradrenaline induced RVSP increase (39.1(3.0) mm Hg), but not to the control range. Metoprolol or carvedilol completely prevented the noradrenaline elicited increases in heart rate (254(7) and 287(20) min-1) and RVdP/dtmax, but prazosin alone had no effect on the heart rate and RVdP/dtmax increase. Thus beta receptor blockade alone failed to significantly influence the noradrenaline induced increase of RVSP despite prevention of the increase in heart rate and RVdP/dtmax. Prazosin had a significant effect on RVSP only in combination with metoprolol. CONCLUSIONS: The combined effect of both alpha and beta blockade exceeds the pure addition of the single effects in the rat right ventricle. Moreover, we speculate that the failure to reduce the noradrenaline induced increase in RVSP by either alpha or beta blockade alone is due to the stimulation of the receptor that is not affected by the respective blocker.     

Can barium support the release of acetylcholine by nerve impulses?

Conventional electrophysiological techniques were used to study the effects of Ba on the release of acetylcholine (ACh) from frog motor nerve terminals. Equimolar substitution of Ba for Ca eliminated end-plate potentials (e.p.ps) without a corresponding decline in the amplitude of the nerve terminal action potential. Miniature end-plate potentials (m.e.p.ps) were readily detectable in Ba solutions despite a depolarized muscle membrane. Studies on the e.p.p. in curarized preparations bathed with different concentrations of Ca and Ba suggest that Ba may compete with Ca in the process by which depolarization of the nerve terminal leads to the release of ACh. Repetitive nerve stimulation at 1 Hz in Ba solutions caused 5-20 fold increases in m.e.p.p. frequencies (7 experiments). Stimulation of Ba-bathed preparations at 10 Hz elevated m.e.p.p. frequencies to very high levels that could not be measured accurately ('100/s). It is suggested that the asynchronous discharge of m.e.p.ps produced by repetitive nerve stimulation is the electrophysiological correlate of the evoked ACh outflow in Ba solutions detected previously by bioassay of ther perfusion fluid.     

Dose-response effects of adrenergic drugs on axial movements of the rat mandibular incisor and on arterial blood pressure

Axial tooth movements and arterial blood pressure were measured following the intravenous injection of 0, 0.01, 0.1, 1, or 10 micrograms/kg of adrenaline, noradrenaline or isoprenaline. Adrenaline caused a dose-dependent, rapid, extrusive tooth movement with a nearly simultaneous increase in blood pressure, followed by a marked intrusive tooth movement and a decrease in blood pressure. Noradrenaline caused a dose-dependent, rapid, extrusive tooth movement and an increase in blood pressure, but a subsequent intrusive tooth movement and decrease in blood pressure were not so marked. Isoprenaline caused a marked intrusive tooth movement and a decrease in blood pressure, without an extrusive tooth movement and increase in blood pressure. The time required to reach the maximum intrusive tooth movement was delayed after that to reach the maximum decrease in blood pressure. The recovery time of the intrusive tooth movement was much more delayed than that of blood pressure. These results suggest that the extrusive movement of the rat incisor was primarily related to the rise of arterial blood pressure due to stimulation of vascular alpha-receptors. It is also suggested that stimulation of beta-receptors would probably cause vasodilatation of arteries that would make the pressure in the small vessels in the microcirculation of the socket fall, so reducing the volume of blood and interstitial fluid in the socket followed by a marked and continuing intrusive tooth movement.     

Differential effects of hippocampal ablations on dispositional and representational memory in the rat.

Long-Evans rats with electrolytic hippocampal ablations exhibited chronic impairment in performance on a spatial delayed nonmatching-to-sample task in the arms of a T-maze. The same rats exhibited only mild deficits, which disappeared with practice, in dispositional memory-dependent discrimination in the stem. Both types of discrimination were learned rapidly preoperatively with no marked positive or negative interaction between types of discrimination. The present results suggest that hippocampal lesions in rats have far more serious consequences on the performance of representational memory-dependent tasks than similar lesions in monkeys. In agreement with our past studies, the present experiment demonstrated that dispositional and representational memory systems in rodents have at least partially distinct anatomical substrates in brain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of angiotensin II on the activities of suprachiasmatic neurons in rat brain slices

The effects of angiotensin II (AII) on the firing rates of suprachiasmatic neurons were determined in rat brain slices. AII in pmol ranges stimulated 25% and inhibited another 25% of 52 irregular firing neurons, while it stimulated 23% and inhibited 4% of 30 regular firing neurons. Three "oscillating" neurons whose firing rates oscillated with rather constant amplitudes and periods were recorded. AII induced the occurrence of oscillation in one unit and modulated the oscillation amplitude of the other two. Pretreatment with saralasin, an AII antagonist, effectively blocked (100%) the actions of AII (n = 5). The present findings suggest that AII may act as an important mediator in the suprachiasmatic nucleus and its mode of action may be variable in different neurons.     

Cholinergic and adrenergic effects of tityustoxin

The effects of purified scorpion toxin (Tityustoxin or TsTX) were investigated on the isolated guinea-pig and rat ileum, rat spleen strip and hen rectal caecum. The contraction of the ileum was due only in part to the release of acetylcholine, whereas the contraction of the spleen strip and the relaxation of the rectal caecum were due to the release of catecholamines.     

Effect of nitroprusside on smooth muscle and adrenergic nerve terminals in isolated blood vessels

Experiments were designed to assess the mode of action of nitroprusside on isolated blood vessels and its relative potency on venous and arterial smooth muscle. Strips from dog blood vessels were mounted in an organ bath for isometric tension recording. Sodium nitroprusside (10(-5) M) depressed the contraction of saphenous vein strips caused by electric stimulation, tyramine, K+, Ba++, norepinephrine and acetylcholine. The depression of the norepinephrine-induced contractions also occurred in a Ca++- free medium and when Ca++ influx was inhibited by verapamil. Nitroprusside reduced the frequency of the spontaneous contractions of strips of portal-mesenteric veins. It depressed the contraction caused by norepinephrine in tibial artery strips more than in saphenous vein strips. Saphenous vein strips were incubated with (3H)norepinephrine and mounted for superfusion and isometric tension recording. Sodium nitroprusside (10(-5) M) had no effect on the basal efflux of 3H compounds. During electric stimulation, it did not change the output of (3H)norepinephrine but increased the outflow of deaminated and O-methylated metabolites. Thus sodium nitroprusside 1) has a direct effect on the smooth muscle cells which is independent of Ca++ influx, 2) depresses contractions of different types of vascular smooth muscle and 3) does not inhibit the release of norepinephrine from the nerve endings.     

Discrimination behavior in the rat: Differential effects of reinforcement and nonreinforcement.

Gave information to a total of 12 male Sprague-Dawley albino rats in 3 experiments about the location of reinforcement and nonreinforcement. Ss then performed a discrimination task choosing among reinforced, nonreinforced, and a 3rd location. In all cases, avoidance of nonreinforcement was substantially greater than approach to reinforcement, indicating the crucial role of nonreinforcement in directing this discrimination behavior. Results of introducing a 50-min delay between information and discrimination trials and presenting other combinations of information confirm these conclusions. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of clozapine and haloperidol on dopamine receptor mRNA expression in rat striatum and cortex

The regulation of the dopamine (DA) receptors is of considerable interest, in part because treatment with antipsychotic drugs is known to upregulate striatal D2-like receptors. While previous studies have focused on the regulation of striatal DA receptors, less is known about the pharmacological regulation of cortical DA receptors. The purpose of this study was to examine the regulation of DA mRNA receptor expression in the cortex compared to the striatum following treatment with antipsychotic agents. Adult male Sprague-Dawley rats were injected daily with haloperidol (2 mg/kg/day), clozapine (20 mg/kg/day) or a control vehicle for a period of 14 days. Following treatment, brains were subjected to in situ hybridization for the mRNAs encoding the five dopamine receptors; only D1, D2, and D3 receptor mRNAs were detected in these regions. Haloperidol tended to either modestly upregulate or have no effect on dopamine receptor mRNAs detected in striatal structures, while clozapine generally downregulated these mRNAs. On the other hand, in the cortex, both drugs had striking effects on D1 and D2 mRNA levels. Cortical D1 mRNA was upregulated by haloperidol, but this effect was primarily restricted to cingulate cortex; clozapine also upregulated D1 mRNA, but primarily in parietal regions. Haloperidol downregulated D2 mRNA in the majority of cortical regions, but most dramatically in frontal and cingulate regions; clozapine typically upregulated this mRNA, but primarily in regions other than frontal and cingulate cortex. These results indicate that clozapine and haloperidol each have regionally-specific effects, and differentially regulate dopamine receptor mRNA expression in striatal and cortical regions of the rat brain.     

Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs

Quinolinate is a tryptophan metabolite and an intermediary in nicotinamide adenine dinucleotide (NAD+) synthesis in hepatocytes. Kynurenine is an upstream metabolite in the same biochemical pathway. Under normal physiological conditions, kynurenine is thought to be produced primarily in the liver as an NAD+ precursor. However, during immune stimulation or inflammation, numerous extrahepatic tissues convert systemic tryptophan to kynurenine, and its concentration subsequently rises dramatically in blood. The fate and role of extrahepatic kynurenine are uncertain. In order to begin addressing this question, the present study was performed to determine which cell types can produce quinolinate from either systemic tryptophan or kynurenine. By using highly specific antibodies to protein-coupled quinolinate, we found that intraperitoneal injections of tryptophan led to increased quinolinate immunoreactivity primarily in hepatocytes, with moderate increases in tissue macrophages and splenic follicles. In contrast, intraperitoneal injections of kynurenine did not result in any significant increase in hepatocyte quinolinate immunoreactivity, but rather led to dramatic increases in immunoreactivity in tissue macrophages, splenic white pulp, and thymic medulla. These findings suggest that hepatocytes do not make significant use of extracellular kynurenine for quinolinate or NAD+ synthesis, and that, instead, extrahepatic kynurenine is preferentially metabolized by immune cells throughout the body. The possible significance of the preferential metabolism of kynurenine by immune cells during an immune response is discussed.     

Protective effects of taurine against reperfusion-induced arrhythmias in isolated ischemic rat heart

The usefulness of computed tomography (CT) in the diagnosis of fish bone impaction in the oesophagus was evaluated. Thirty-two patients were examined by plain X-ray followed by direct oesophagoscopy for suspected fish bone impaction. Among 25 cases in which fish bones were actually removed, foreign bodies were not clearly demonstrated by plain X-ray in 14 cases (56 per cent). Eleven cases underwent CT prior to the oesophagoscopic examination. Fish bones were clearly demonstrated by CT in all patients. CT also clearly visualized secondarily-induced inflammatory changes in the neighbouring structures. In order to confirm this result, we made a simulation model of oesophageal fish bone impaction, using fish bones of three different species surrounded by a water bag. In comparison with plain X-ray, CT depicted a superior image of fine fish bones and provides extremely useful information for the management of impacted fish bones in the oesophagus.