Biomedical subjects

H Majewski

Publications and source records attributed to H Majewski.

103 records · Page 6Linked to original sources

PubMedDate not supplied

Adrenaline activation of prejunctional beta-adrenoceptors and hypertension.

Rats implanted with osmotic minipumps containing adrenaline (0.2 ml, 2.9 mM) developed increased systolic and diastolic blood pressures, whereas blood pressures in rats implanted with osmotic minipumps containing the same amount of noradrenaline did not differ from those of sham-operated control rats. Heart rates did not differ from control in either treatment group. Concomitant administration of metoprolol (2.5 mg/kg, i.p., twice daily) abolished the effect of adrenaline-treatment on blood pressure. Plasma concentrations of adrenaline and noradrenaline released from the minipumps were 17 nM and 2.4 nM, respectively The atria accumulated 56 pmol/g of adrenaline released from the minipump. In isolated atria, adrenaline (10 nM) increased noradrenergic transmitter release by acting on prejunctional beta-adrenoceptors. Incubation of isolated atria with adrenaline led to the accumulation of 46 pmol/g. This adrenaline was released as a cotransmitter and mediated a positive feedback effect on transmission which was disrupted by metoprolol (0.1 micro M). It is suggested that the increase in blood pressure produced in rats by chronic treatment with adrenaline is due to facilitation of noradrenergic transmission to cardiovascular effector tissues. Such an effect may be involved in the development of stress-induced hypertension.

Animals↗

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Effects of alpha 1- and alpha 2-adrenoceptor blocking drugs on noradrenaline release rate in anesthetized rabbits.

[3H]noradrenaline was infused intravenously into pentobarbitone-anesthetized 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. The effects of a series of selective alpha 1- and alpha 2-adrenoceptor blocking drugs on the noradrenaline release rate and noradrenaline clearance were investigated. Yohimbine (1 mg/kg i.v.), rauwolscine (1 mg/kg i.v.), corynanthine (1 mg/kg i.v.), prazosin (0.3 and 1 mg/kg i.v.), phenoxybenzamine (4 mg/kg i.v.), and sodium nitroprusside (10 micrograms/kg/min i.v.) decreased the plasma noradrenaline clearance. The selective alpha 2-adrenoceptor blocking drugs yohimbine and rauwolscine, as well as phenoxybenzamine, increased the noradrenaline release rate more than equihypotensive doses of the directly acting vasodilators hydralazine and sodium nitroprusside. The selective alpha 1-adrenoceptor blocking drugs prazosin and corynanthine increased the noradrenaline release rate less than equihypotensive doses of the vasodilators. These results suggest that, in vivo, blockade of alpha 2-adrenoceptors results in increased noradrenaline release, probably due to blockade of inhibitory presynaptic alpha 2-adrenoceptors at sympathetic nerve endings. Blockade of alpha 1-adrenoceptors, on the other hand, appears to depress baroreceptor-mediated increases in noradrenaline release in response to a fall in blood pressure.

Adrenergic alpha-Antagonists↗

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Local modulation of noradrenaline release in vivo: presynaptic beta 2-adrenoceptors and endogenous adrenaline.

Isoprenaline bitartrate (0.5 microgram/kg/min i.v.) increased the rate of noradrenaline release into the circulation of pentobarbitone-anesthetized rabbits. This increase was much greater than that produced by an equi-hypotensive dose of the vasodilator hydralazine (0.2 mg/kg i.v.), suggesting that it was only partly due to baro-reflex activation of sympathetic nerves. This facilitatory effect of isoprenaline was also observed in the nephrectomized, pithed rabbit, with electrically stimulated sympathetic outflow, ruling out central nervous system and renin-angiotensin effects. ICI 118,551 HCl (0.3 mg/kg + 0.1 mg/kg/h i.v.) blocked the isoprenaline-induced hypotension, but did not affect the isoprenaline-induced tachycardia, suggesting that it selectively blocked beta 2-adrenoceptors. ICI 118,551 totally abolished the isoprenaline-induced increase in noradrenaline release, suggesting a beta 2-effect. Atenolol (0.3 mg/kg + 0.1 mg/kg/h) blocked the isoprenaline-induced tachycardia, a beta 1-effect, but only slightly attenuated the isoprenaline-induced increase in noradrenaline release. Atenolol by itself decreased heart rate and arterial pressure, but there was no reflex rise in the noradrenaline release rate, which suggests that atenolol impairs baroreceptor activation of sympathetic nerves. In another series of experiments, also in the pentobarbitone-anesthetized rabbit, adrenaline was released into the circulation by splanchnic nerve stimulation. This resulted in prolonged increases of adrenaline levels in heart tissue. After the plasma adrenaline levels had returned to prestimulation values, the rate of noradrenaline release into the plasma was enhanced. This increase was not observed in rabbits treated with either desipramine HCl (1 mg/kg i.v.) or propranolol HCl (2 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

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Modulation of noradrenaline release in the pithed rabbit: a role for angiotensin II.

This study in the pithed rabbit with electrically stimulated sympathetic outflow (spinal region, T-8; 3 Hz) was conducted to determine the contribution of the renin-angiotensin system to noradrenaline release in vivo. The rate of noradrenaline release (spillover) into the plasma was determined from the endogenous plasma noradrenaline level and the simultaneously determined noradrenaline plasma clearance. In the pithed rabbit, infusion of angiotensin II (0.1 microgram/kg/min i.v.) failed to increase the noradrenaline release rate and only slightly increased blood pressure. On the other hand, the angiotensin-converting enzyme inhibitor captopril (1 mg/kg i.v.) decreased both blood pressure and the noradrenaline release rate. Bilateral nephrectomy was performed to reduce endogenous angiotensin II formation; and in this case, infusion of angiotensin II markedly increased the noradrenaline release rate and blood pressure, whereas captopril had no effect on either parameter. These results suggest that angiotensin II modulates noradrenaline release in vivo through activation of facilitatory prejunctional angiotensin II receptors, and that in the pithed rabbit these receptors are probably maximally activated by endogenously synthesized angiotensin II. The actions of angiotensin II on noradrenaline release open the possibility that increases in blood pressure in the pithed rabbit--by decreasing renin release via intrarenal baroreceptors and hence decreasing angiotensin II formation--may lead to decreased noradrenaline release. This was investigated using phenylephrine (6 micrograms/kg/min i.v.), a selective alpha 1-adrenoceptor agonist, and adrenaline (1 microgram/kg/min i.v.), and alpha 1/alpha 2-agonist. Both drugs increased blood pressure and decreased the noradrenaline release rate. After bilateral nephrectomy, the inhibitory effect of phenylephrine on noradrenaline release was abolished, whereas that of adrenaline was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

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Dual effect of adrenaline on noradrenaline release in the pithed rabbit.

We examined the effects of adrenaline on the noradrenaline release rate and plasma catecholamine levels in the pithed rabbit with electrically stimulated sympathetic outflow (3 Hz). Adrenaline (0.06 micrograms/kg/min) increased the rate of noradrenaline release into the plasma. This increase was prevented by propranolol (0.2 mg/kg + 0.1 mg/kg/h) and probably involves activation of presynaptic beta-adrenoceptors. A higher dose of adrenaline (1.0 micrograms/kg/min) significantly reduced the noradrenaline release rate. The reduction was "reversed" to a facilitatory effect by phenoxybenzamine (4 mg/kg). Propranolol alone slightly inhibited the noradrenaline release rate. After pretreatment with desipramine (1.0 mg/kg + 0.2 mg/kg/h), the inhibitory effect of propranolol on noradrenaline release was more pronounced and blood pressure was also lowered. However, in rabbits pretreated with captopril (1 mg/kg) in addition to desipramine, the sympathoinhibitory effect of propranolol was not observed. These results suggest that adrenaline can activate either presynaptic beta-adrenoceptors to increase noradrenaline release or, in higher doses, presynaptic alpha-adrenoceptors to inhibit noradrenaline release in vivo. The decrease in the noradrenaline release rate produced by propranolol alone may not be due to blockade of facilitatory presynaptic beta-adrenoceptors, but rather to depression of renin secretion. This would decrease angiotensin II formation and hence decrease the presynaptic release-enhancing effect of angiotensin II.

Angiotensin II↗

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Inhibition by hydralazine of the conversion of dopamine to noradrenaline in rat atria in vitro and in vivo.

1. Hydralazine (10 to 2000 microgramol/l) produced a concentration-dependent inhibition of the conversion of (3H)-dopamine to (3H)-noradrenaline in rat isolated atria. 2. In rats treated with hydralazine (2 mg/kg, i.p.), there was an inhibition of the conversion of (3H)-dopamine to (3)-noradrenaline in the intact artia in vivo. 3. Hydralazine treatment may result in the appearance of dopamine as a significant co-transmitter in noradrenergic nerves, and this may contribute to the antihypertensive effect of hydralazine.

Animals↗

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Hypertension through adrenaline activation of prejunctional beta-adrenoceptors.

1. Adrenaline can enhance the stimulation-induced release of transmitter noradrenaline in sympathetically innervated tissues by activating prejunctional beta-adrenoceptors. 2. Adrenaline incorporated into sympathetic transmitter stores by neuronal uptake can be subsequently released as a co-transmitter and can then activate prejunctional beta-adrenoceptors, thus completing a facilitatory feedback loop. 3. Rats chronically treated with adrenaline develop elevated blood pressures compared to control rats. beta-Adrenoceptor blockade prevents the rise in blood pressure. 4. Activation by adrenaline of facilitatory prejunctional beta-adrenoceptors of sympathetic nerves innervating cardiovascular effector tissues may explain adrenaline-induced rises in blood pressure.

Adrenal Medulla↗

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Effects of isotonic saline loading on renal tubular and neurogenic dopamine release in conscious rabbits.

1. This study was designed to investigate the effects of isotonic saline loading on renal tubular and neurogenic dopamine (DA) in conscious rabbits. 2. Isotonic saline loading did not affect mean arterial pressure, heart rate or renal blood flow but markedly increased urine volume, sodium excretion and DA excretion. 3. Renal DA spillover was not affected by venous emptying, while renal noradrenaline (NA) spillover tended to decrease during saline loading. The ratio of % renal DA spillover to % renal NA spillover increased to 2.3 +/- 0.6 (P < 0.05) 3 h after saline loading. 4. Isotonic saline loading increased renal tubular DA production but had little effect on neurogenic DA release.

Analysis of Variance↗

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Facilitation of noradrenaline release by isoprenaline is not mediated by angiotensin II in mouse atria and rat tail artery.

The hypothesis that facilitation of noradrenaline release by prejunctional beta-adrenoceptors is linked to the local generation of angiotensin II was investigated in rat tail artery and mouse atria which were incubated with [3H]-noradrenaline. The outflow of radioactivity induced by electrical field stimulation of the tissues was taken as an index of noradrenaline release. In mouse atria, angiotensin II (0.01 microM) enhanced the stimulation-induced (S-I) noradrenaline release and this was blocked by saralasin (0.1 microM). Isoprenaline (0.01 microM) also enhanced the S-I release of noradrenaline, but this was not blocked by either saralasin (0.1 microM and 0.3 microM) or captopril (5 microM). Furthermore, the facilitatory effects of angiotensin II (0.1 microM) and isoprenaline (0.1 microM) were additive. In rat tail artery, the facilitatory effect of angiotensin II (0.01 microM) on noradrenaline release was blocked by saralasin (0.1 microM). The facilitatory effect of isoprenaline (0.1 microM) was blocked by propranolol (1 microM) but not by saralasin (0.1 microM) nor captopril (5 microM). These results indicate that beta-adrenoceptor-mediated facilitation of noradrenaline release occurs independently of angiotensin II in mouse atria and rat tail artery.

Angiotensin II↗

PubMedDate not supplied