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Biomedical subjects

H Majewski

Publications and source records attributed to H Majewski.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effect of captopril on blood pressure responses to enkephalins in chloralose-anaesthetized rats.

Captopril lowered blood pressure in chloralose-anaesthetized rats and enhanced the depressor responses to metenkephalin and D-Ala-metenkephalinamide to the same extent. Since metenkephalin is a much better substrate than D-Ala-metenkephalinamide for dipeptidylcarboxypeptidase, some mechanism other than inhibition of this enzyme appears to be responsible for the enhancement by captopril of the responses to opioids. When the blood pressure had been lowered by haemorrhage, naloxone was no more effective than saline control in restoring blood pressure. However, when captopril was given after haemorrhage, the blood pressure was further lowered, and then naloxone produced a significant restoration. Hydralazine given after haemorrhage also caused a further lowering of blood pressure, then naloxone produced a lesser restoration of blood pressure than in haemorrhage plus captopril experiments. The results suggest that release of endogenous opioids may contribute to the fall in blood pressure upon bleeding.

Anesthesia↗
PubMed1985

Neuronal and postjunctional components in the blood pressure effects of dopamine and bromocriptine in rabbits.

We have studied the contribution of neuronal and postjunctional dopamine (DA) receptors and of the DA1 and DA2 receptor subtypes to the blood pressure effects of DA and bromocriptine in the rabbit. The norepinephrine release rate, i.e., the rate of entry of endogenous norepinephrine into the plasma, was derived from the plasma level of endogenous norepinephrine and the plasma [3H]norepinephrine clearance. Bromocriptine (40 micrograms kg-1) lowered the norepinephrine release rate and the arterial blood pressure both in anesthetized rabbits and in pithed rabbits with electrically stimulated sympathetic outflow. These effects were antagonized by the selective DA2 antagonist domperidone but not by the selective DA1 antagonist SCH 23390. DA (10-160 micrograms kg-1 min-1) dose-dependently increased the norepinephrine release rate and caused only transient hypotension in anesthetized rabbits. However, after treatment with desipramine, DA did not change the norepinephrine release rate and produced a persistent fall in blood pressure. When DA and domperidone were given simultaneously to desipramine-treated rabbits, the hypotensive effect of DA was unchanged, but now DA increased the norepinephrine release rate. When DA and SCH 23390 were given simultaneously to desipramine-treated rabbits, DA failed to lower blood pressure and decreased the norepinephrine release rate. Propranolol did not change the effects of DA in desipramine-treated rabbits. These results suggest that bromocriptine decreases blood pressure by activating ganglionic and/or prejunctional, inhibitory DA2 receptors in the peripheral sympathetic nervous system. DA also activates these receptors, but in addition releases norepinephrine in the manner of an indirectly acting sympathomimetic amine and activates postjunctional vascular DA1 receptors, and the latter seems to be the main component in DA-induced hypotension.

Anesthesia↗
PubMed1984

Adrenaline mediates a positive feedback loop in noradrenergic transmission: its possible role in development of hypertension.

Adrenaline activates prejunctional beta-adrenoceptors of the beta 2-subtype on sympathetic nerve terminals and enhances noradrenergic transmission. Adrenaline can be incorporated in transmitter stores of noradrenergic nerves and, when released as a cotransmitter, activates the prejunctional beta 2-adrenoceptors, thereby mediating autofacilitation of noradrenergic transmission. Adrenaline released from the adrenal medulla in stress may be incorporated in noradrenergic transmitter stores and reach a sufficient concentration as a cotransmitter to activate the autofacilitatory feedback loop involving prejunctional beta 2-adrenoceptors, resulting in prolongation of the increases in vasomotor tone and cardiac activity that occur acutely: with frequent repetition of stress, there may be progression into a hypertensive state. In accord with this hypothesis, adrenaline administration produces persistent increases in blood pressure in rats, and plasma levels of adrenaline are elevated in a proportion of hypertensive patients; furthermore, repeated stress produces prolonged increases in blood pressure in animals and man.

Animals↗
PubMed1983

Modulation of noradrenaline release in the conscious rabbit through alpha-adrenoceptors.

The effects of selective alpha 1- and alpha 2-adrenoceptor antagonists and agonists on the noradrenaline release rate and plasma catecholamine levels were studied in the conscious rabbit. The selective alpha 2-adrenoceptor blocking drugs yohimbine and rauwolscine (1 mg/kg i.v.) increased the rate of noradrenaline release into the plasma and the plasma noradrenaline and adrenaline levels. This was associated with a rise in blood pressure. The selective alpha 1-blocking drug corynanthine (1 mg/kg i.v.) had no effect. Intravenous infusions of the selective alpha 2-adrenoceptor agonist alpha-methylnoradrenaline (2 micrograms/kg per min) and the alpha 1-agonist phenylephrine (6 micrograms/kg per min) produced equipressor responses. However, only alpha-methylnoradrenaline decreased the noradrenaline release rate and the plasma noradrenaline and adrenaline levels, effects which were blocked by yohimbine. The results are compatible with, but of course do not prove the hypothesis that in the conscious rabbit, noradrenaline release from sympathetic nerves is modulated through presynaptic alpha 2-adrenoceptors. Adrenaline release from the adrenal medulla may also be subject to alpha 2-adrenergic modulation.

Adrenergic alpha-Agonists↗
PubMed1983

Evidence for a physiological role of presynaptic alpha-adrenoceptors: modulation of noradrenaline release in the pithed rabbit.

Rabbits were pithed and the preganglionic nerves at T 8 were stimulated continuously at a frequency of 3 Hz. 3H-noradrenaline was infused to reach a steady-state plasma level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was also determined and the rate of noradrenaline release into the plasma was then derived. The noradrenaline plasma clearance was decreased by guanethidine (7.5 mg/kg), desipramine (1 mg/kg), yohimbine (1 mg/kg) and rauwolscine (1 mg/kg). It was unaffected by corynanthine (1 mg/kg), prazosin (0.1 mg/kg), alpha-methylnoradrenaline (2 micrograms/kg per min) and clonidine (1 micrograms/kg per min). The electrical stimulation resulted in an increase in blood pressure without an increase in heart rate. Both adrenaline and noradrenaline were detected in the plasma. It is likely that the noradrenaline was of neuronal origin as guanethidine decreased its plasma level. The alpha 2-adrenoceptor-selective blocking drugs yohimbine and rauwolscine increased the noradrenaline release rate and only slightly decreased blood pressure. On the other hand, the alpha 1-adrenoceptor-selective blocking drugs corynanthine and prazosin had no effect on the noradrenaline release rate and decreased blood pressure more markedly. The alpha 2-adrenoceptor-selective agonists alpha-methylnoradrenaline and clonidine both decreased the noradrenaline release rate. This effect was blocked by yohimbine, and for the case of clonidine, not blocked by corynanthine. Plasma adrenaline levels were increased by yohimbine and rauwolscine, but not by corynanthine and prazosin. Clonidine reduced the plasma adrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1983

Modulation of noradrenaline release through activation of presynaptic beta-adrenoreceptors.

On peripheral noradrenergic nerve endings there exist beta-adrenoreceptors activation of which results in an enhanced release of noradrenaline in response to nerve stimulation. These presynapatic beta-adrenoreceptors do not appear to be activated by neuronally-released noradrenaline. However, adrenaline may be a physiological activator during enhanced adrenomedullary secretion. Adrenaline can also be incorporated into the noradrenergic transmitter stores and be released as a co-transmitter. Under these conditions presynaptic beta-adrenoreceptors may be activated by neuronally-released adrenaline, thus forming a 'positive feedback loop'. The release of adrenaline from the adrenal medullae may also be modulated through facilitatory beta-adrenoreceptors, but the release of noradrenaline from noradrenergic nerves in the central nervous system is not. The facilitatory presynaptic beta-adrenoreceptors appear to be in the main of the beta 2-subtype although precise receptor characterization has not been carried out. Increased activation of presynaptic beta-adrenoreceptors by adrenaline may be implicated in the development of essential hypertension. Part of the antihypertensive action of beta-adrenoreceptor blocking drugs may be due to blockade of these facilitatory presynaptic beta-adrenoreceptors.

Adrenal Medulla↗
PubMed1982

Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart.

The outflow of noradrenaline, 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) from rabbit perfused hearts was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs and without nerve stimulation, the outflow of endogenous noradrenaline over a period of 108 min averaged 0.17 pmol X g-1 X min-1 and the outflow of DOPEG 2.1 pmol X g-1 X min-1. The outflow of DOMA was below the detection limit (less than 0.13 pmol X g-1 X min-1). The effect of perfusion with (-)-noradrenaline 0.1, or 10 mumol/l for 18 min was then investigated. As the concentration of nor-adrenaline increased so did the outflow of DOPEG. Moreover, DOMA was found in the venous effluent during and after perfusion with noradrenaline 1 or 10 mumol/l. The increase in the outflow of DOPEG and DOMA was almost abolished when cocaine 10 mumol/l was present during the perfusion with noradrenaline 1 mumol/l. The release of endogenous noradrenaline by sympathetic nerve stimulation or tyramine 10 mumol/l, but not the release evoked by nicotine 30 mumol/l, was accompanied by an increase in the outflow of DOPEG; an outflow of DOMA was not observed. It is concluded that, in the rabbit perfused heart, DOPEG is an important metabolite of endogenous noradrenaline. DOMA is at best a minor product, either when the neurones are at rest or when noradrenaline is released by sympathetic nerve stimulation, nicotine or tyramine. DOMA is formed in detectable amounts when the tissue is exposed to a high concentration of exogenous noradrenaline. Like DOPEG, it is formed intraneuronally. The results confirm and extend those obtained previously on guinea-pig incubated atria. They make it unlikely that, in these tissues at least, DOMA formation is one of the physiological pathways of noradrenaline catabolism.

Animals↗
PubMed1982

The noradrenaline rate in the anaesthetized rabbit: facilitation by adrenaline.

1. 3H-Noradrenaline was infused intravenously into pentobarbitone anaesthetized rabbits to reach a steady-state plasma 3H-noradrenaline level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was determined simultaneously and the rate of noradrenaline release was then derived. 2. Pargyline, amezinium, desipramine and guanethidine all reduced the noradrenaline plasma clearance. The noradrenaline release rate was decreased by desipramine, guanethidine and clonidine. 3. Adrenaline (6 nmol/kg i.v. twice) enhanced the noradrenaline release rate by 53%. This effect was apparent after the plasma adrenaline has returned to basal levels. The adrenaline levels in sympathetically innervated tissues were elevated at this time. 4. When the rabbits were pretreated with either propranolol HCl (1 mg/kg i.p.) to block beta-adrenoceptors, or desipramine HCl (1 mg/kg i.v.) to block neuronal uptake, the facilitatory effect of adrenaline was abolished. Noradrenaline (6 nmol/kg i.v. twice) had no effect on the noradrenaline release rate. 5. These findings suggest that if the sympathetic transmitter stores contain sufficient adrenaline neuronally released adrenaline may modulate noradrenaline release in vivo by activating facilitatory presynaptic beta-adrenoceptors.

Anesthesia↗
PubMed1981

An interaction between prejunctional alpha-adrenoceptors and prejunctional beta-adrenoceptors.

The ability os isoprenaline to enhance transmitter release from sympathetic nerves in rat atria incubated with [3H]noradrenaline was assessed under three conditions of prejunctional alpha-adrenoceptor activation: in the presence of phentolamine, in the presence of noradrenaline, and in the absence of either drug. Isoprenaline-induced enhancement of transmitter release was inversely related to the degree of activation of prejunctional alpha-adrenoceptors. Thus there appears to be an interaction between the prejunctional alpha-adrenoceptor inhibitory mechanism and the prejunctional beta-adrenoceptor facilitatory mechanism. In rabbit ear arteries incubated with [3H]noradrenaline, isoprenaline facilitated transmitter release in the presence but not in the absence of phentolamine. Therefore in some tissues it may be necessary to block prejunctional alpha-adrenoceptors before prejunctional beta-adrenoceptors can be demonstrated.

Animals↗
PubMed1981

Adrenaline-induced hypertension in rats.

1. Rats implanted with osmotic minipumps delivering adrenaline intraperitoneally at the rate of 2.9 nmol/h had significantly higher systolic and diastolic pressures from days 2 to 6 after implantation than sham-operated controls rats. 2. Concomitant treatment with metoprolol tartrate (2.5 mg/kg, intraperitoneally, twice daily) prevented the elevation in blood pressure induced by adrenaline from osmotic minipumps. Such metoprolol treatment did not affect the blood pressure of controls rats. 3. Noradrenaline administered intraperitoneally from osmotic minipumps at the rate of 2.9 nmol/h had no significant effect on blood pressure over a 6-day period of observation. 4. Tachyphylaxis developed to the acute pressor responses to intermittent intravenous infusions of adrenaline in doses of 0.78 microgram (4.24 nmol) every 10 min, but after 14 days of such treatment systolic and diastolic blood pressures were significantly greater than in controls rats. 5. It is suggested that the increase in blood pressure produced by chronic treatment with adrenaline is due to the uptake and accumulation of adrenaline in noradrenergic nerve terminals, from which it is subsequently released as a cotransmitter that mediates a positive feedback loop on transmission by acting on prejunctional beta-adrenoceptors.

Animals↗
PubMed1981

Activation of prejunctional beta-adrenoceptors in rat atria by adrenaline applied exogenously or released as a co-transmitter.

1 Adrenaline (10 nM) significantly enhanced the stimulation-induced efflux of radioactivity from rat atria previously incubated with [3H]-noradrenaline ([3H]-NA). This effect was abolished by metoprolol (.01 muM). 2 Adrenaline in a higher concentration (1 muM) and NA (1 muM) significantly reduced the stimulation-induced efflux of radioactivity. However, in the presence of phenoxybenzamine (10 muM), adrenaline (1 muM) enhanced the efflux, whereas NA (1 muM) had no effect. 3 In rat isolated atria pre-incubated with adrenaline and then incubated with NA, both catecholamines were taken up and were released by field stimulation. When pre-incubation was with adrenaline and incubation was with [3H]-NA, metoprolol decreased the stimulation-induced efflux of radioactivity. This effect did not occur if the atria were pre-incubated with NA instead of adrenaline, suggesting tht neuronally released adrenaline activates prejunctional beta-adrenoceptors. 4 In conscious rats, intravenously administered adrenaline (6.0 and 0.6 nmol/kg) was taken up and retained in the atria and could be released by field stimulation. The release was calcium-dependent from these rats up to 24 h after administration.

Animals↗
PubMed1980

Adrenaline activation of prejunctional beta-adrenoceptors in guinea-pig atria.

1. Adrenaline in a concentration of 1.0 microM depressed the stimulation-induced efflux of tritium from the guinea-pig atria incubated with [3H]-noradrenaline, whereas adrenaline in a concentration of 0.5 nM significantly enhanced the stimulation-induced efflux of tritium. This enhancement was blocked by metoprolol (0.1 microM) and thus appears to be mediated by beta-adrenoceptors. 2. In guinea-pig atria incubated with unlabelled adrenaline and then with [3H]-noradrenaline, both catecholamines were released by field stimulation. In such atria metoprolol, practolol, oxprenolol or propranolol decreased the stimulation-induced efflux of tritium. These effects did not occur if the atria were incubated with unlabelled noradrenaline and then with [3H]-noradrenaline, suggesting that neuronally released adrenaline activates prejunctional beta-adrenoceptors. 3. The effect of oxprenolol in decreasing the release of tritium from guinea-pig atria, incubated with unlabelled adrenaline and then with [3H]-noradrenaline was greater in the presence of phentolamine. This may reflect the alpha-adrenoceptor blocking activity of oxprenolol.

Animals↗