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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 8 imidazoline derivatives on the cardiovascular system and their acute toxicity were investigated. In anesthetized rats, K-6341 and K-6343 produced relatively long-lasting elevation of blood pressure. This hypertensive response was prevented by prazosin. In contrast, K-4011, K-3827 and K-4300 exerted long-lasting hypotensive actions. Norepinephrine-induced increase in blood pressure was competitively antagonized by these three derivatives. Therefore, the hypertensive and hypotensive actions of imidazoline derivatives are conceivably exerted by activating and blocking alpha 1-adrenoceptors. In the isolated guinea-pig atrial preparations, K-4011, K-3827, K-6341 and K-6343 produced positive inotropic responses which were independent of beta-adrenoceptor activation. The positive inotropic effect of K-6341, which was the most potent, was specifically attenuated or abolished by diltiazem, suggesting that a change in Ca2+ movement across the cell membrane is contributing to K-6341-induced increase in atrial contractions. The main symptoms of mice manifested when injected with imidazoline derivatives were a decrease in spontaneous movement, exophthalmos, an increase in palpebral opening, paralysis of four limbs and respiratory depression. Acute LD50 values of imidazoline derivatives in mice (i.v., i.p.) were between these of tolazoline and naphazoline.
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PMID:Pharmacological studies of imidazoline derivatives. III. Actions on cardiovascular system and acute toxicity. 373 60

The role of the central noradrenergic system in the supraoptic neuroendocrine regulation was investigated using slices of the guinea pig hypothalamus. Noradrenaline produced a complex membrane effect comprising two distinct depolarizations: one, associated with a moderate increase in input resistance and resulting in an augmentation of the spontaneous firing rate; the other, unaccompanied by a detectable change in input resistance and resulting in depression of the firing rate. The former depolarization was reproducible by applying specific alpha-agonist, phenylephrine, whereas the latter was induced by a beta-adrenergic agonist, isoproterenol. The actions of phenylephrine and isoproterenol were blocked by phentolamine and propranolol, respectively. Amplitude of the phenylephrine-induced depolarization was voltage-dependent with the estimated reversal potential of about - 115 mV and changed as a function of [K+]o. On the contrary, amplitude of the isoproterenol-induced depolarization was voltage-independent and was insensitive to changes in external concentrations of K+, Na+, Cl- and Ca2+. We conclude that catecholamines directly modulate the activity of supraoptic neurons through two functionally distinct adrenoceptive sites on neurosecretory cells. The activation of alpha-receptors may increase cellular excitability through suppression of membrane K+ conductance while the activation of beta-receptors would depress neuronal firings, possibly through some mechanism which is not directly linked to ionic channels.
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PMID:The effects of catecholamines on electrical activity of neurons in the guinea pig supraoptic nucleus in vitro. 376 10

Infection often complicates renal failure and frequently causes death, but the association between renal failure, impaired immunity and infection has not been proved. A recent study showed that patients on dialysis did not show an expected leucocytic response to infection, suggesting that the blunted response was evidence of the immunocompromised state of the uraemic patient. In this study, the relationship between leucocytic responses and infectious challenge was investigated in an animal model of chronic renal failure. Bacteraemia, peritonitis and a chronic lung infection were induced in normal and uraemic rats; the leucocytic response was then monitored. In all three infections, the total white blood cell response was significantly less in the uraemic animals. Neutrophil numbers actually increased, but this response was disguised by a pronounced depression in lymphocyte numbers. Our conclusion is that, although the leucocytic response of the uraemic host to infection may be depressed, the changes to individual leucocyte components in the peripheral blood are sufficiently characteristic to provide useful evidence of infection.
Nephron 1985
PMID:Host immune status in uraemia. VI. Leucocytic response to bacterial infection in chronic renal failure. 388 87

This study examines the effects of 12 months of endurance exercise training (cycling, walking and jogging) on lipid profiles, glucose metabolism, blood pressure, anemia and psychological function in 14 hemodialysis patients. Maximal aerobic capacity (VO2max) increased 18% in the exercisers (p less than 0.01), but did not change in 11 controls. This was associated with a reduction in depression, a decrease in dosages of antihypertensive medications, a significant increase in hematocrit and hemoglobin levels (red cell mass rose, plasma volume did not change), a decrease in plasma triglyceride by 23% (p less than 0.05) and an increase in high-density lipoprotein cholesterol (HDL-C) levels by 21% (p less than 0.01) (both HDL-C and triglyceride levels worsened in the sedentary controls), and an 18% increase in glucose disappearance rates (p less than 0.05) in spite of a 52% decrease in fasting insulin levels (p less than 0.01), suggesting that insulin sensitivity improved. These results demonstrate that some of the complications present in hemodialysis patients may be caused by their sedentary life-style, rather than endstage renal disease itself. This suggests that rehabilitation through exercise is possible for these patients. By reducing coronary risk factors in hemodialysis patients, exercise training may also decrease their heightened morbidity and mortality from atherosclerotic complications. These possibilities need to be examined in a longitudinal study.
Nephron 1986
PMID:Exercise training reduces coronary risk and effectively rehabilitates hemodialysis patients. 396 Feb 42

The effects of catecholamines on spinal motoneurones and spinal reflex discharges were investigated in the isolated spinal cord of newborn rat. Noradrenaline (NA), adrenaline (Adr), dopamine (DA) and isoproterenol (Iso) caused depolarization of the motoneurones in a dose-dependent manner. The depolarizing action persisted in Ca2+-deficient Krebs solution. The order of potency was Adr greater than NA greater than DA much greater than Iso. The effects of NA and Adr on the monosynaptic reflex discharge varied; depression, potentiation or depression followed by potentiation. The polysynaptic reflex discharge was consistently depressed. DA depressed both the mono- and polysynaptic reflex discharges in all the preparations. Tyramine and adamantanamine induced a response similar to that to DA rather than to NA. Depolarization of the motoneurones and the effects on the spinal reflex discharges induced by all the catecholamines were decreased by phentolamine or phenoxybenzamine but not by propranolol or haloperidol. It is suggested that the endogenous catecholamines, mainly DA, depolarize the motoneurones and depress the mono- and polysynaptic reflex discharges through an alpha-adrenoceptor in the spinal cord of the newborn rat.
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PMID:Effects of catecholamines on spinal motoneurones and spinal reflex discharges in the isolated spinal cord of the newborn rat. 399 39

Potassium and magnesium deficiency have been reported as risk factors for experimental gentamicin nephrotoxicity. Amiloride, a potassium-sparing diuretic, also leads to increased renal magnesium reabsorption. Amiloride, 2 mg/kg/day, was given to groups of 8-12 Fischer 344 rats receiving gentamicin, 20 mg/kg b.i.d., for 3, 7, 10 and 14 days. Control animals received the vehicle for gentamicin, amiloride alone or gentamicin alone. The degree of renal failure and weight loss were similar in gentamicin and gentamicin + amiloride groups at all time points despite increases in serum potassium and magnesium in the amiloride-treated animals. Tubular dysfunction as assessed by depression of renal cortical slice uptake of p-aminohippurate and N-methylnicotinamide was not improved by the addition of amiloride. In addition, a comparable degree of tubular necrosis and regeneration was observed in all gentamicin-treated groups. Maximum gentamicin concentrations in the renal cortex did not differ. Thus, despite reduction of urinary losses of potassium and magnesium with resultant increased serum values, amiloride did not protect against experimental gentamicin nephrotoxicity. The tubular electrolyte wasting noted clinically is likely to be a result, rather than a cause of proximal tubular cell damage.
Nephron 1985
PMID:Effect of amiloride on experimental gentamicin nephrotoxicity. 400 Mar 46

Controversy exists over the nature of the abnormality in cardiac sympathetic nerves in heart failure. In the cardiomyopathy of the Syrian hamster, reduction in tissue stores and increased turnover of norepinephrine is clearly associated with excessive sympathetic stimulation but in animal models and humans with heart failure secondary to mechanical overload there is evidence for depression of neuronal uptake. Because norepinephrine is both released and taken up by sympathetic fibers it is impossible to assess norepinephrine kinetics in an intact heart without separating these two functions. A technique for doing so has recently been developed in normal dogs and we therefore acquired similar data in humans with heart failure secondary to chronic pressure and volume overload. The technique involves the combination of transient norepinephrine tracer coronary sinus outflow in relation to intravascular and interstitial references after simultaneous injection into the left coronary artery and the measurement of endogenous norepinephrine concentrations in artery and coronary sinus. We found a marked reduction in cardiac norepinephrine release and uptake in a group of patients with clinical left ventricular failure secondary to mechanical overload, relative to a group of patients with no failure. Norepinephrine balance and overflow across the heart were not significantly different. We conclude that there is hypofunction of the cardiac sympathetic nerves in heart failure secondary to mechanical overload and that traditional methods are inadequate in assessing cardiac norepinephrine kinetics when there are simultaneous changes in neuronal uptake and release.
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PMID:Tracer norepinephrine kinetics in coronary circulation of patients with heart failure secondary to chronic pressure and volume overload. 405 51

1. Noradrenaline and adrenaline reduce the output of acetylcholine by the guinea-pig ileum longitudinal strip by up to 80%, both in resting conditions and after stimulation. The effect is graded with dose, and is detectable with noradrenaline 2 x 10(-7) g/ml. Adrenaline is approximately 4 times as active as noradrenaline, and its action after being washed out is more persistent.2. If resting output is high, both amines have a proportionately greater effect and their action, as dosage is increased, is to reduce resting output to a basal level, relatively constant from strip to strip, of about 10 ng/g/min.3. With stimulation, the effect of the amine is greater at low frequencies, when the output per volley is high, than at high frequencies. The effect is reduced by increasing the number of shocks delivered. There thus appears to be a basal output per volley, of the order of 1-2 ng/g/volley, which can be reached either by relatively rapid stimulation, by prolonged stimulation, or by treatment with these amines.4. If noradrenaline is applied during continued stimulation at 40/min, the depression of acetylcholine output during its presence is followed by an augmented output when the drug is withdrawn. The magnitude of this "overshoot" increases with the duration of noradrenaline exposure.5. Phenylephrine 4 mug/ml. and amphetamine 20 mug/ml. reduced the acetylcholine output, but isoprenaline 1 mug/ml., dopamine 1 mug/ml. and methoxamine 10 mug/ml. were ineffective.6. Phenoxybenzamine reduced the resting output and increased the stimulation output. Of the two other blocking agents examined, phentolamine had no effect on either resting or stimulation output and ergotamine transiently reduced stimulation output. The effect of phenoxybenzamine was not due to a reaction with either adrenoceptive or muscarinic receptors.7. Phenoxybenzamine, phentolamine and ergotamine abolished the effect of adrenaline and noradrenaline on both resting output and on output in response to stimulation.8. In strips obtained from animals treated with reserpine and guanethidine, a rise in resting acetylcholine output and in stimulation output at low frequencies was found. In these conditions, noradrenaline was still effective.9. Reducing the hydroxytryptamine content of the strips by treatment with p-chloro-(+/-)-phenylalanine did not significantly affect acetylcholine output.10. It is concluded that acetylcholine output by the nervous networks of the longitudinal strip is under the normal control of the sympathetic by a species of presynaptic inhibition mediated by alpha receptors. This implies that for a tissue under dual autonomic control, withdrawal of sympathetic control will lead to a parasympathetic response which is not only unopposed but also itself enhanced.
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PMID:The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. 430 25

Adrenergic and cholinergic agonists and antagonists were applied microelectrophoretically to over 700 neurons in the cat supraoptic nucleus, 20 percent of which were antidromically identified as neurosecretory cells. Norepinephrine uniformly depressed all sensitive cells. Acetylcholine caused both muscarinic depression and nicotinic excitation which were antagonized by atropine and dihydro-beta-erythroidine, respectively. These results support the hypothesis that norepinephrine and acetylcholine are directly involved in controlling the release of antidiuretic hormone.
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PMID:Supraoptic neurosecretory cells: adrenergic and cholinergic sensitivity. 439 31

1 Noradrenaline and clonidine were applied by microiontophoresis to single neurones in the cerebral cortex and medullary reticular formation of anaesthetized rats.2 Of a total of 247 neurones studied, 79% of medullary units and 60% of cortical units responded in the same manner to both noradrenaline and clonidine. The usual response was a depression of neuronal firing rate.3 It proved possible to antagonize some responses to both substances by the microiontophoresis of bulbocapnine, whilst leaving unaffected similar responses to 5-hydroxytryptamine.4 On 13% of the cells, clonidine produced an increase of firing rate. This effect could not be attributed to a post-synaptic antagonism of tonically released endogenous noradrenaline, but may indicate a presynaptic action of clonidine, reducing noradrenaline release.5 These observations are thought to support the idea that clonidine may have an agonist action on noradrenaline receptors in the brain.
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PMID:On the mechanism of action of clonidine: effects on single central neurones. 445 50


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