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

This study has determined the propranolol content of Purkinje fibers associated with antiarrhythmic and electrophysiological actions of the drug both in vivo and in vitro. The minimum effective tissue content of propranolol that consistently reversed a sustained ouabain-induced ventrivular tachycardia in vivo after i.v. propranolol was between 6.7 and 11.1 micron g/g of tissue. Propranolol doses producing Purkinje fiber contents of less than 6.7 micron g/g failed to revert the arrhythmia but did ponotropic responses to 0.5 micron g/kg of isoproterenol. The in vivo minimum effective tissue content was produced in isolated Purkinje fibers perfused with Tyrode's solution containing 1.7 X 10(-6) M propranolol. In Purkinje fibers this concentration of propranolol depressed the rate of phase 4 depolarization previously enhanced by ouabain 2.1 X 10(-7) M. Propranolol, 1.7 X 10(-6) M, did not alter membrane responsiveness and only slightly accelerated repolarization at 5 minutes. Propranolol, 0.85 X 10(-6) M, did not significantly depress the ouabain-enhanced rate of phase 4 depolarization but did attenuate the response to epinephrine through beta blockade. This study indicated that the initial direct action of propranolol in reverting a ouabain-induced ventricular tachycardia to a sinus rhythm in the dog is depression of automaticity.
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PMID:Association of in vivo and in vitro propranolol levels in canine Purkinje fibers with antiarrhythmic effects. 1 29

1. The effects of propranolol, atenolol (ICI 66,082), practolol and pindolol on heart rate and maximal left ventricular dp/dt, atrioventricular conduction time, mean aortic flow and diastolic blood pressure during cardiac pacing were investigated over a wide dose range (0.025-4.0 mg/kg, i.v.) in dogs anaesthetized with pentobarbitone.2. Propranolol and atenolol produced similar reductions in haemodynamic parameters. Propranolol had no further effect in dogs pretreated with atenolol. 3. Practolol tended to cause smaller reductions in the haemodynamic parameters than either propranolol or atenolol. Subsequent administration of propranolol still had some depressant activity. 4. Pindolol produced a biphasic response, with depression of cardiac function at the low doses (0.025 and 0.1 mg/kg), but a reversal of effect as the dose was increased. 5. It is therefore concluded that, in anaesthetized dogs, the intrinsic activity of practolol and pindolol limits the fall in heart rate, cardiac conduction, aortic flow and maximal dp/dt observed with beta-adrenoceptor blockade. With pindolol, however, the influence of intrinsic activity is observed only in high doses related to beta-adrenoceptor blockade.
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PMID:The influence of the intrinsic sympathomimetic activity of beta-adrenoceptor antagonists on haemodynamic effects in anaesthetized dogs. 3 81

The effects on GH and PRL secretion of several pharmacological agents known to modify central neurotransmitter action were determined in unanesthetized male rats. Phenoxybenzamine, an alpha-adrenergic blocker (5 mg/kg iv), abolished episodic GH secretion and caused elevation of serum PRL levels. Propranolol, a beta-adrenergic blocker (5 mg/kg iv), had no effect on GH secretion and caused a small but significant depression in PRL levels. Parachlorophenylalanine methyl ester, an inhibitor of tryptophan hydroxylase (300-350 mg/kg ip), resulted in significant inhibition of GH pulsatile secretion and suppressed PRL levels. Methysergide hydrogen maleinate (25 mg/kg iv), a serotonin receptor antagonist, also inhibited GH secretion, but produced a transient stimulation in PRL levels. Atropine sulfate (2 mg/kg iv) caused significant suppression in GH secretion, but had no effect on PRL. Picrotoxin, a gamma-aminobutyric acid antagonist, in a subconvulsive dose of 1-3 mg/kg iv, also depressed GH episodic secretion but did not affect PRL levels. These results indicate that several neurotransmitters, i.e., norepinephrine, serotonin, acetylcholine, and gamma-aminobutyric acid, found in high concentration in the hypothalamus, influence GH and PRL secretion.
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PMID:Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat. 3 92

Coronary haemodynamic and metabolic effects of propranolol and glyceryl trinitrate were studied in 12 patients with coronary artery disease and 5 without coronary heart disease, at rest and during tachycardia stress. Propranolol-associated reductions in indices of myocardial oxygen demand, left ventricle work, tension time, and left ventricle oxygen utilisation (LVVO2) were reversed when heart rate was controlled by atrial pacing. Adding glyceryl trinitrate at rest also restored heart rate but decreased the left ventricular work index and tension time index as coronary resistance declined paradoxically. Tachycardia-related increases in tension time index and LVVO2 were unchanged after propranolol, and ischaemia (angina, ST depression, and reduced lactate extraction) was not altered in most of the patients. During tachycardia, the addition of glyceryl trinitrate decreased the tension time index and LVVO2; angina recurred in only 4 patients, and ST depression and lactate extraction improved. Similar haemodynamic changes occurred in the patients with normal coronary arteries. In contrast with propranolol administered alone, propranolol plus glyceryl trinitrate enhances tachycardia tolerance and prevents tachycardia-induced manifestations of ischaemia. This action is attributed to glyceryl trinitrate-associated improvement in the adequacy of myocardial perfusion.
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PMID:Coronary and myocardial metabolic effects of combined glyceryl trinitrate and propranolol administration. Observations in patients with and without coronary disease. 10 30

1 N-2-O-dibutyryl adenosine 3',5'-monophosphate (db cyclic AMP), adrenaline and aminophylline produce a potentiation of the tension developed (Td) and the maximum rate of rise of tension (dT/dt max) in the rat isolated diaphragm during indirect electrical stimulation. Aminophylline and db cyclic AMP also produce the same effect during direct stimulation. 2 Propranolol produced a depression of the action of adrenaline on Td and dT/dt max during indirect stimulation of the diaphragm. On the other hand, the potentiating actions of db cyclic AMP and of aminophylline on Td and dT/dt max during indirect stimulation were unaffected by propranolol. 3 The results support the idea that cyclic AMP may be involved not only in regulating the processes associated with synthesis, mobilization and storage of transmitter in the motor nerve terminal, but also in modifying some metabolic processes which regulate the function of the contractile elements.
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PMID:The effects of cyclic N-2-O-dibutyryl- adenosine 3',5'-monophosphate, adrenaline and aminophylline on the isometric contractility of the isolated hemidiaphragm of the rat. 16 33

The responses of type A atrial receptors to graded infusions of saline and large doses of propranolol were examined in anesthetized cats. Infusion of saline raised the mean atrial pressure, but usually the amplitude of the atrial a wave was reduced. In general the receptor discharge was unaffected. Propranolol reduced the discharge from the control level when it was injected in doses no less than 4 mg/kg. Infusions of saline after propranolol resulted in an increase in the discharge and the increase was related to the amplitude and/or initial pressure of the a wave. In one case the discharge after propranolol was less than that when the atrium was widely slit open. It is concluded that at least part of the effect of the drug is due to a direct depression of the receptor rendering it less sensitive to the stretch provided by atrial contraction. The demonstration of a stimulus-response relationship between the a wave and the receptor discharge at low levels of activity suggests that under normal conditiions the receptor operates on a plateau of maximum activity, thus making a response to small changes in stimulus strength obscure.
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PMID:Effect of propranolol on the relationship between atrial systolic pressure and type A atrial receptor discharge in cats. 18 31

SQ 11725 was approximately 1/3 as potent as propranolol in blocking the stimulant effects of isoproterenol in vitro, but was 2-4 times more potent than propranolol in blocking the diastolic blood-pressure and heart-rate responses, respectively, to isoproterenol in vivo. SQ 11725 had no depressant effects on contractile force of isolated guinea pig atrial muscle at the largest bath concentration studied (1000 mug/ml), whereas propranolol caused significant depression at a concentration of 1-10 mug/ml. Propranolol was at least 20-30 times more depressant than SQ 11725 to canine myocardium in vivo. SQ 11725 was more effective then propranolol in inhibiting tachycardic responses to treadmill exercise in unanesthetized dogs. The duration of blockade of the heart-rate response to exercise or to isoproterenol administration in the unanesthetized dog was approximately 5 times greater with SQ 11725 than with propranolol.
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PMID:Pharmacology of nadolol (SQ 11725), a beta-adrenergic antagonist lacking direct myocardial depression. 24 55

The effects of propranolol, digoxin and combination therapy (/D) on the resting and exercise ECG were studied in ten normal subjects and 20 patients with coronary artery disease (CAD) given a sequence of oral placebo, propranolol, P/D, digoxin and placebo, for two week periods. Digoxin produced a significant decrease in T-wave amplitude and often resulted in ST segment depression in the resting ECG. Propranolol, digoxin, and P/D tended to decrease the QTc interval and prolong the PR interval. However, CAD patients were more sensitive to PR prolongation than normals while receiving propranolol or digoxin alone. Propranolol therapy did not significantly affect the ST segment of the exercise ECG in the normal subjects or the CAD patients without an ischemic control exercise ECG. By contrast, 50 per cent of the normal subjects developed "false-positive" ischemic ST segment responses to exercise while receiving digoxin of P/D and three of eight CAD patients without ischemic control exercise ST segments had a similar response to digoxin or P/D. In 12 CAD patients with ischemic control exercise ST segments, propranolol did not affect the amount of ST segment depression at the onset of angina or the maximum amount of ST segment depression. Digoxin or P/D both uniformly increased the maximum amount of ST segment depression which was greater with digoxin than P/D. However, the maximum heart rate on P/D was significantly reduced as compared to that on digoxin. It is concluded that (1) CAD patients are more sensitive to propranolol or digoxin-induced AV block than normals, (2) propranolol does not change the magnitude of ischemic exercise ST segment depression, (3) digoxin increases ischemic exercise ST segment depression and results in a high incidence of false-positive exercise tests, and (4) the addition of propranolol to digoxin attenuates the effects of digoxin on the exercise ST segment.
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PMID:The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram. 31 42

During the last four years we have used a new cardioselective beta-adrenergic blocking substance, ICI 66.082 (atenolol or Tenormin), alone or in combination with other drugs for treatment of hypertension in a total of 104 patients, including 15 with a chronic obstructive lung disease. Fifty-one patients started treatment with atenolol because of side-effects--especially from the central nervous system--during previous treatment with non-selective beta-blockers, mostly propranolol (Inderal). Mean duration of treatment was 16 months (range 8--36) and mean dosage 163 mg/day. In 18 patients treatment with Tenormin was withdrawn, but only in 10 of them could this be referred to side-effects. Of the 51 patients who complained of or showed side-effects from another beta-blocker, 80% were improved after changing to Tenormin. Of the patients with side-effects from the central nervous system, 73% improved, especially those who complained of nightmares, hallucinations, insomnia or mild depression.
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PMID:Long-term clinical experience with atenolol--a new selective beta-1-blocker with few side-effects from the central nervous system. 36 88

Stimulation of cutaneous or muscle nerve as well as activation of ventral roots L6--S1 led to inhibition of vagal bradycardia evoked by noradrenaline, in unanesthetized decerebrated cats. Unnociceptive stimulation of m. gastrocnemius in unrestrained cats evoked contraction of the muscle and was followed by depression of the cardiac component of baroreceptive reflex. Propranolol had no effect on this response, while methylatropin abolished it completely.
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PMID:[Inhibition of the cardiochronotropic component of baroreceptor reflexes following activation of somatic afferents]. 58 67


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