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Biomedical subjects

B Szabo

Publications and source records attributed to B Szabo.

At least 19 recordsLinked to original sources
PubMed1995

Involvement of peripheral presynaptic inhibition in the reduction of sympathetic tone by moxonidine, rilmenidine and UK 14304.

We studied the possibility that presynaptic inhibition of transmitter release from postganglionic sympathetic neurons contributes to the overall reduction of sympathetic tone produced by moxonidine, rilmenidine and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline tartrate (UK 14304). In pithed rabbits without electric stimulation, moxonidine, rilmenidine and UK 14304 caused a long-lasting, > 10 min, increase in arterial pressure. Heart rate was not changed. In pithed rabbits in which sympathetic tone was created by electric stimulation through the pithing rod (2 Hz), the same doses of moxonidine, rilmenidine and UK 14304 caused only a brief, < 10 min, blood pressure rise. Heart rate was decreased, as were the plasma concentrations of noradrenaline and adrenaline. Dose-response curves for the effects on the plasma noradrenaline concentration (stimulated pithed rabbits) were compared with previously obtained dose-response curves for depression of renal sympathetic nerve activity (conscious rabbits). For each drug, the curve describing peripheral presynaptic inhibition and the curve describing central sympathoinhibition were very similar. Both the power and the dose dependence of the peripheral inhibitory effect support its contribution to the overall decrease in sympathetic tone produced by clonidine-like drugs in intact animals. The peripheral effect in all likelihood consists in activation of presynaptic alpha 2-autoreceptors. The agreement of the dose-response curves for the peripheral and for the central effect supports the view that the central effect, like the peripheral one, is mediated through alpha 2-adrenoceptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

Involvement of alpha 2-adrenoceptors in the cardiovascular effects of moxonidine.

The central sympathoinhibition caused by moxonidine has been explained by activation of alpha 2-adrenoceptors on the one hand, and by an action at imidazoline I1 receptors on the other hand. In order to examine these possibilities, effects of moxonidine were compared with those of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), an alpha 2-adrenoceptor agonist with very low affinity for I1 receptors, in conscious rabbits. The interaction with yohimbine, an alpha 2-adrenoceptor antagonist with very low affinity for imidazoline I1 receptors, was also studied. Moxonidine 3-100 micrograms kg-1 and UK 14304 1-30 micrograms kg-1 i.v. elicited similar effects: they decreased arterial blood pressure after a transient increase, decreased renal sympathetic nerve activity (recorded with chronically implanted electrodes), decreased heart rate and decreased the plasma noradrenaline concentration. Yohimbine given i.v. antagonized the effects of moxonidine and of UK 14304 in a similar manner. Yohimbine injected into the cisterna magna (i.c.) prevented the hypotension but did not change the decrease in plasma noradrenaline and heart rate, again in the case of both moxonidine and UK 14304. The agreement of the effect patterns of moxonidine and UK 14304, and the similar antagonism of yohimbine against either drug, demonstrate involvement of alpha 2-adrenoceptors in their central sympathoinhibitory action. The resistance of the bradycardia and the plasma noradrenaline fall against yohimbine i.c. indicates a contribution of presynaptic alpha 2-adrenergic inhibition of transmitter release from postganglionic sympathetic neurons to the overall reduction of sympathetic tone.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1992

Mapping in the atrioventricular junction.

Ectopic conduction is defined as the premature exit of the cardiac impulse from the specialized conduction system across a damaged Purkinje-ventricular muscle interface. This anomalous form of atrioventricular (AV) conduction was induced in the dog heart by lidocaine injection of the His bundle-interventricular septum interface and by ischemic damage of the AV junction subsequent to anterior septal artery ligation in the dog heart. The electrocardiogram (ECG) manifestation of ectopic conduction is the loss of initial forces and replacement of the Q waves with delta waves. In order to verify these effects, the authors devised a multi-electrode, malleable plaque (63 electrode sites) that could be secured at the AV junction during venous occlusion in the open-chest, anesthetized dog. Preliminary maps indicated a dramatic change in activation that proceeded from apex to base of the heart in the control state and reversed after ischemic damage to the His bundle. In vitro, it was possible to induce ectopic conduction by lidocaine injection at the interface of the right bundle branch and septal muscle. Microelectrode studies demonstrated that foot potentials, for example, electrotonic, or subthreshold potentials mediated the connection from Purkinje to muscle in the damaged zone. In a recent set of experiments in vivo, subthreshold stimulation (STS) was delivered to simulate electrotonic potentials to the His bundle region, and right ventricular apex, using multipolar electrode catheters. In the normal heart, STS delivered as DC constant current or pulse trains (1000 Hz, 50 ms pulse duration) induced shortened P-R intervals and delta waves with or without bundle branch block patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of the dopamine D2 receptor agonist quinpirole on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits.

Cardiovascular and sympathetic nervous system effects of the dopamine D2 receptor-selective agonist quinpirole were studied in anesthetized rabbits. Sodium nitroprusside was administered for comparison. The animals received a tracer infusion of [3H] norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and epinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. Quinpirole (100 micrograms kg-1 + 5 micrograms kg-1 min-1 i.v.) lowered blood pressure and renal vascular resistance. The firing rate of the renal sympathetic nerves was increased, but there was no reflex tachycardia. Despite the increase in renal sympathetic firing, the renal spillover of norepinephrine into blood was decreased. The increase in total body norepinephrine spillover during quinpirole-induced hypotension was less than expected from baroreflex activation. Effects of quinpirole were antagonized by domperidone (1000 micrograms kg-1 + 200 micrograms kg-1 h-1). The distinguishing feature of this study is the simultaneous measurement of sympathetic firing and norepinephrine spillover in the same organ, the kidney, under conditions of intact sympathetic impulse traffic. Quinpirole activated presynaptic D2 receptors and thus reduced the released norepinephrine per action potential. Consequences of the presynaptic inhibition were reductions of blood pressure and renal vascular resistance and absence of reflex tachycardia.

Animals↗
PubMed1992

Effects of inhibitors of neuronal uptake of 5-HT on sympathetic cardiovascular regulation.

The effect on sympathetic cardiovascular regulation of inhibition of the high-affinity neuronal uptake of 5-hydroxytryptamine (5-HT) by fluvoxamine, citalopram, and fluoxetine was studied in anesthetized rabbits. The mean arterial pressure, postganglionic renal sympathetic nerve activity, heart rate, clearance of [3H]norepinephrine from plasma and the plasma norepinephrine concentration were measured, and from the latter two parameters the spillover of norepinephrine into the blood was calculated. The effect of fluvoxamine and fluoxetine on the uptake of [3H]5-HT into platelets was also examined. Of four increasing doses of fluvoxamine (0.6, 1.7, 5, and 15 mg/kg i.v.) and citalopram (0.3, 1, 3, and 9 mg/kg i.v.), only the two highest ones decreased the renal sympathetic nerve activity, heart rate, and clearance of [3H]norepinephrine from plasma. Only the highest of four increasing doses of fluoxetine (0.2, 0.6, 1.7, and 5 mg/kg i.v.) inhibited sympathetic nerve activity. However, lower doses of fluvoxamine (0.6 and 1.7 mg/kg i.v.) and fluoxetine (0.6 and 1.7 mg/kg i.v.) already markedly inhibited the uptake of [3H]5-HT into platelets. The data indicate that selective inhibition of neuronal uptake of 5-HT has no effect on central sympathetic regulation in anesthetized rabbits. The sympathoinhibition observed at high doses of fluvoxamine and citalopram is probably due to inhibition of the neuronal uptake of norepinephrine.

Analysis of Variance↗
PubMed1992

Effect of yohimbine on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits.

The function of presynaptic alpha-2 adrenergic autoinhibition of norepinephrine release was studied in anesthetized rabbits (alfadolone + alfaxalone) with uninterrupted sympathetic impulse traffic. The animals received a tracer infusion of [3H]norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. The results were used to calculate the renal fractional [3H]norepinephrine extraction, the renal removal and spillover of norepinephrine, the total body [3H]norepinephrine clearance and total body norepinephrine spillover. Sodium nitroprusside (10-80 micrograms kg-1 min-1 i.v.), which was infused to modulate sympathetic activity through the baroreceptors, caused hypotension and increased the renal sympathetic firing rate and the renal as well as total body norepinephrine spillover. Increases of total body norepinephrine spillover were much higher than increases of renal spillover. Yohimbine (1 mg kg-1 + 0.2 mg kg-1 hr-1 i.v.) caused slight central sympathoexcitation. In addition, it enhanced the renal and total body spillover of norepinephrine at any given firing rate of the renal sympathetic nerves. The distinguishing feature of this study is the measurement of sympathetic firing rate and norepinephrine spillover in one and the same organ, the kidney. The results demonstrate that the alpha-2 adrenergic autoinhibition of norepinephrine release normally operates in the kidney with intact sympathetic impulse traffic. They also suggest its operation in other peripheral sympathetically innervated tissues.

Anesthesia↗
PubMed1991

The noradrenaline uptake inhibitor, (+)-oxaprotiline, but not the inactive enantiomer, (-)-oxaprotiline, inhibits sympathetic nerve activity in the rabbit: involvement of adrenoceptors.

The effect of the enantiomers of oxaprotiline on the sympathetic nervous system was studied in anesthetized rabbits. (+)-Oxaprotile 0.2, 0.6 and 1.8 mg kg-1 dose dependently reduced prostganglionic renal sympathetic nerve activity and the clearance of [3H]noradrenaline from the plasma but increased the plasma noradrenaline concentration. The spillover of noradrenaline into the blood was not changed significantly, nor were blood pressure and heart rate, except transiently. The same doses of (-)-oxaprotiline had no effect on any of the parameters measured. (+)-Oxoprotiline also reduced lumbar preganglionic sympathetic nerve activity. The effect of (+)-oxaprotiline on renal sympathetic nerve activity was only minimally antagonized by yohimbine given alone. (+)-Oxaprotiline also inhibited renal sympathetic nerve activity after treatment with prazosin and propranolol. Subsequent administration of yohimbine restored sympathetic nerve activity to the value seen before the administration of (+)-oxaprotiline. The results show that inhibition of the re-uptake of released noradrenaline is the basis of the sympathoinhibition produced by (+)-oxaprotiline. Noradrenaline probably acts on alpha 2-adrenoceptors in the central nervous system to produce sympathoinhibition.

Animals↗
PubMed1991

Effects of p-chloroamphetamine on release of [3H]gamma-aminobutyric acid from slices of rat caudate-putamen.

The effect of endogenous serotonin on the release of [3H]gamma-aminobutyric acid ([3H]GABA) from slices of rat caudate-putamen was studied. p-Chloroamphetamine was used to release endogenous serotonin. p-Chloroamphetamine (100 nM) enhanced the release of [3H]GABA induced by 20 mM K+, while 1000 nM p-chloroamphetamine decreased it. The 5-HT3 receptor antagonists ICS 205-930 (50 nM) and MDL 72222 (100 nM) prevented this facilitation caused by 100 nM p-chloroamphetamine. ICS 205-903 (50 nM), when used alone, reduced the release of [3H]GABA caused by 23 mM K+. This finding confirmed the hypothesis that endogenous serotonin can enhance the release of [3H]GABA via 5-HT3 receptors. In contrast, an effect of 5-HT1 and 5-HT2 receptors could not be clearly established. It is likely that the release of endogenous GABA from striatonigral GABA neurons may also be affected by serotonin via 5-HT3 receptors.

Animals↗
PubMed1990

Early and delayed afterdepolarizations associated with cesium chloride-induced arrhythmias in the dog.

Monophasic action potentials (MAPs) were utilized to examine the basis for cesium-induced arrhythmia in the dog. Cesium chloride (1 mmol/kg i.v.) produced an immediate prolongation of MAP (250 +/- 11 to 396 +/- 34 ms, p less than 0.05). Coupled premature ventricular beats (345 +/- 46 ms) and polymorphic ventricular tachycardia developed in association with early afterdepolarizations during the first 1-3 min after cesium administration. A slowing of the sinus heart rate with vagus nerve stimulation exacerbated the arrhythmia. During the subsequent 7 min, the MAP duration decreased from 396 +/- 34 to 316 +/- 19 ms. At 8-10 min, the premature ventricular beats were associated with delayed afterdepolarizations in the MAP recordings. However, there was no change in the coupling intervals of the premature ventricular beats (351 +/- 29 ms). Ventricular arrhythmias and delayed afterdepolarizations during this phase were exacerbated by increasing the heart rate with atrial pacing. T wave alternans and U wave formation in the ECG were associated with early or delayed afterdepolarizations in MAP. Cesium chloride (1 mmol) injected into the left anterior descending coronary artery produced local MAP prolongation and ventricular bigeminy. Although the MAP duration returned to predrug values after intracoronary cesium injection, the severity of ventricular arrhythmia increased with succeeding doses. These data suggest that early and delayed afterdepolarizations, T wave alterations, and ventricular beats can be dissociated from the initial action potential prolongation with cesium and closely resemble altered calcium transients observed in vitro.

Action Potentials↗
PubMed1990

Peripheral presynaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits.

The function of presynaptic angiotensin II receptors at postganglionic sympathetic terminal axons under conditions of uninterrupted sympathetic impulse traffic was studied in anesthetized rabbits (alfadolone + alfaxalone). Mean arterial pressure, postganglionic renal sympathetic firing rate, the arterial plasma noradrenaline concentration, and heart rate were measured before (basal values) and at the end of 4-min infusions of sodium nitroprusside. Angiotensin II (20 or 100 ng kg-1 min-1) caused dose-dependent increases of basal mean arterial pressure and decreases of basal sympathetic nerve activity and heart rate, but did not change the basal plasma noradrenaline concentration. Moreover, it shifted the sympathetic nerve activity-plasma noradrenaline relationship in a manner indicating an increase of the average release of noradrenaline per action potential. Angiotensin II at 100 ng kg-1 min-1 had an additional effect, at any given blood pressure, sympathetic nerve activity and heart rate were lower than in the controls. Captopril (1 mg kg-1 followed by 1 mg kg-1 h-1) caused no change in any parameter. The results demonstrate that exogenous angiotensin II activates release-facilitating receptors at postganglionic sympathetic neurons in rabbits with ongoing sympathetic nerve activity. Endogenous angiotensin II, however, played no role in cardiovascular regulation under the present, acute experimental conditions. Vasopressin, which was studied for comparison, lacked a presynaptic effect on the release of noradrenaline but caused sympathoinhibition by an action on a central component of the baroreflex.

Anesthesia↗
PubMed1989

Peripheral presynaptic and central effects of clonidine, yohimbine and rauwolscine on the sympathetic nervous system in rabbits.

The function of presynaptic alpha 2-autoreceptors at postganglionic sympathetic neurones under conditions of normal, ongoing sympathetic impulse traffic was studied in anaesthetized rabbits (alfadolone + alfaxalone). Clonidine was used as an alpha 2-adrenoceptor agonist, and yohimbine and rauwolscine were used as antagonists. Mean arterial pressure, postganglionic renal sympathetic firing rate, arterial plasma noradrenaline concentration and heart rate were measured before (basal values) and at the end of 3-min infusions of sodium nitroprusside and phenylephrine, which were given to modulate efferent activity in the sympathetic nervous system through the baroreflex. The nitroprusside- and phenylephrine-induced changes of mean arterial pressure produced the expected changes in sympathetic nerve activity, plasma noradrenaline and heart rate. Clonidine (5 micrograms kg-1 + 0.5 micrograms kg-1 min-1) reduced the basal mean arterial pressure, sympathetic nerve activity and heart rate. It also reduced the nitroprusside-induced increase in the plasma noradrenaline level without changing the nitroprusside-induced increase in sympathetic firing. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that clonidine inhibited both sympathetic tone centrally and the average release of noradrenaline per action potential peripherally. Yohimbine (1 mg kg-1 + 0.1 mg kg-1 h-1) and rauwolscine (0.5 mg kg-1 + 0.1 mg kg-1 h-1) increased the basal plasma noradrenaline level without any increase of renal sympathetic nerve activity. They also enhanced the nitroprusside-induced increase in plasma noradrenaline without any enhancement of the nitroprusside-induced increase in sympathetic firing. The hypotensive response to nitroprusside was attenuated, whereas the heart rate response was augmented. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that the main effect of yohimbine and rauwolscine was to increase the average release of noradrenaline per action potential. The simultaneous measurement of postganglionic sympathetic nerve activity and the arterial plasma noradrenaline concentration proved suitable to differentiate central (or ganglionic; this distinction was not possible) effects of alpha 2-adrenoceptor ligands from peripheral presynaptic effects. The results show that endogenous presynaptic, alpha 2-adrenergic autoinhibition of noradrenaline release from postganglionic sympathetic neurones operates physiologically in anaesthetized rabbits with ongoing, uninterrupted sympathetic nerve activity. The results also indicate that blockade of alpha 2-autoreceptors enhances the sympathetic reflex compensatory response to a hypotensive stimulus.

Animals↗
PubMed1989

Facilitation of the release of noradrenaline: an extra-adrenal effect of adrenocorticotropic hormone.

Effects of ACTH-(1-24) on the release of noradrenaline from postganglionic sympathetic neurones were studied in rabbits. In the isolated perfused rabbit heart, ACTH-(1-24) (0.1-100 nmol/l) increased the overflow of noradrenaline elicited by sympathetic nerve stimulation at 1 Hz, an effect that persisted in the presence of propranolol and cocaine. In pithed rabbits with electrically stimulated sympathetic outflow (2 Hz), ACTH-(1-24) (0.03-1 microgram/kg per min) increased the plasma noradrenaline concentration as well as the calculated rate of entry of noradrenaline into the plasma, but decreased arterial blood pressure by a direct vasodilator effect. In anaesthetized rabbits, ACTH-(1-24) (0.1-1 microgram/kg per min) also increased the plasma noradrenaline concentration; the higher dose in addition reduced the blood pressure and increased the firing rate of renal sympathetic nerves; however, the rise in plasma noradrenaline was greater than would have been expected from the increase in sympathetic firing rate alone. It is concluded that ACTH exerts two primary effects on the cardiovascular system of the rabbit: presynaptic facilitation of the noradrenaline release and postsynaptic vasodilation. The vasodilation leads to a baroreceptor-mediated reflex increase in sympathetic tone. The low concentrations of ACTH required suggest that presynaptic facilitation may occur in vivo, at least when the secretion of ACTH is high.

Adrenergic Fibers↗
PubMed1988

ACTH increases noradrenaline release in the rabbit heart.

The effects of ACTH on the release of noradrenaline and the increase of heart rate produced by sympathetic nerve stimulation (1 Hz) were studied in isolated perfused rabbit hearts. ACTH-(1-24) 0.1-100 nmol/l increased the stimulation-evoked overflow of noradrenaline concentration-dependently, reversibly and up to two-fold. The basal outflow of noradrenaline, the basal heart rate and the stimulation-evoked increase in heart rate were not changed. Human ACTH-(1-39) also increased the evoked overflow of noradrenaline. The effect of ACTH-(1-24) 0.3 nmol/l persisted after blockade of beta-adrenoceptors with propranolol and blockade of neuronal catecholamine uptake by cocaine. ACTH-(1-24) 3 nmol/l did not change the removal of noradrenaline from the perfusion fluid, when hearts were perfused with medium containing 59 nmol/l noradrenaline. The results show that ACTH increases the action potential-evoked release of noradrenaline from cardiac postganglionic sympathetic neurones, probably by activating specific presynaptic ACTH receptors. The high potency of ACTH suggests that these presynaptic receptors may be activated in vivo by circulating ACTH under certain pathophysiological conditions.

Animals↗
PubMed1988

Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits.

1. Opioid agonists influence isolated cardiovascular tissues from rabbits, as well as the cardiovascular system of pithed rabbits, through presynaptic receptors on postganglionic sympathetic nerve fibres. The present experiments were carried out in order to study effects which result from activation of these receptors in anaesthetized rabbits. 2. In pithed rabbits with electrically stimulated sympathetic outflow, infusion of [D-Ala2-D-Leu5]-enkephalin (DADLE) 10 micrograms kg-1 min-1 and dynorphin-(1-13) (dynorphin) 1 microgram kg-1 min-1 decreased the plasma noradrenaline concentration, mean arterial pressure (MAP) and heart rate. The effects of dynorphin and, less completely, those of DADLE were antagonized by the peripherally selective opioid antagonists N-methyl naloxone bromide (NMN) 1.3 mg kg-1 and N-methyl levallorphan methanesulphonate (NML) 1-3 mg kg-1. 3. In pentobarbitone-anaesthetized rabbits, DADLE 3-30 micrograms kg-1 min-1 and dynorphin 0.3-3 micrograms kg-1 min-1 decreased the plasma noradrenaline concentration and MAP. The highest dose of dynorphin also decreased heart rate, whereas DADLE 10 micrograms kg-1 min-1 caused slight cardioacceleration. The effects of DADLE but not those of dynorphin decreased upon repeated administration. 4. The effects of dynorphin 10 micrograms kg-1 min-1 were abolished or greatly attenuated by NMN 1.3 mg kg-1 and NML 3 mg kg-1. In contrast, the antagonists reduced only slightly the blood pressure-lowering effect of DADLE 10 micrograms kg-1 min-1 and did not reduce significantly the effects of DADLE on the plasma noradrenaline level and heart rate. 5. It was concluded that systemically administered dynorphin produces sympatho-inhibition and an ensuing fall in blood pressure by an action at peripheral receptors, in all probability presynaptic Kappa-receptors on postganglionic sympathetic nerve fibres. The effects of DADLE are more complex and may involve both central and peripheral components.

Animals↗
PubMed1987

Presynaptic opioid receptors in the portal vein of the rabbit.

The effects of opioids on sympathetic neuroeffector transmission were studied in superfused strips of the portal vein of the rabbit. In the first series of experiments, the tissue was stimulated electrically every 10 min with 10 pulses at 8 Hz and a current strength of 200 mA. The contractions evoked were concentration dependently inhibited by the slightly kappa-selective agonist ethylketocyclazocine and by the delta-selective agonists [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Pen2,D-Pen5]enkephalin (DPDPLE). The mu-selective agonist [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) had no effect. The estimated EC50 values for ethylketocyclazocine and DADLE were 5.5 X 10(-8) and 2.9 X 10(-8) mol/l, respectively. Naloxone shifted the concentration-response curves of ethylketocyclazocine and DADLE to the right; the estimated Kb values were (1.7 +/- 0.4) X 10(-8) mol/l and (2.9 +/- 0.8) X 10(-8) mol/l, respectively. The delta-selective antagonist ICI 174864 antagonized only the inhibitory effect of DADLE but not that of ethylketocyclazocine. In the second series of experiments, the tissue was preincubated with [3H]noradrenaline then superfused and stimulated electrically three times for 3 min at 1 Hz and a current strength of 100 mA. Ethylketocyclazocine and DADLE inhibited the evoked overflow of tritium. The inhibition produced by ethylketocyclazocine was antagonized by naloxone. Our results show for the first time that opioid agonists inhibit noradrenaline release and hence, neurogenic vasoconstriction in a vein. As in other cardiovascular tissues of the rabbit, the presynaptic opioid receptors are of the kappa- and delta- but not the mu-type.

Animals↗
PubMed1987

ACTH increases noradrenaline release in pithed rabbits with electrically stimulated sympathetic outflow.

ACTH 0.03-1 microgram/kg per min i.v. increased the noradrenaline spillover rate (the rate at which endogenous noradrenaline enters into plasma) and the plasma noradrenaline concentration in pithed rabbits with electrically stimulated sympathetic outflow. ACTH 0.1 and 1 microgram/kg per min decreased the mean arterial pressure (MAP). The effects of ACTH persisted in animals treated with propranolol. Corticosterone 10 micrograms/kg per min had no effect on the neurochemical and circulatory parameters. ACTH 0.03 and 1 microgram/kg per min increased plasma corticosterone and cortisol concentrations; the two doses of ACTH had approximately the same effect. The plasma corticosterone concentration reached after infusion of corticosterone 10 micrograms/kg per min was about twice that obtained after ACTH 0.03 or 1 microgram/kg per min. In a second series of experiments, a pressor dose of noradrenaline (1 or 2 micrograms/kg per min) was infused i.v. into pithed rabbits. ACTH 0.03 and 1 microgram/kg per min decreased blood pressure and increased heart rate in these animals. The results suggest that high doses of ACTH increase noradrenaline release by an action on postganglionic sympathetic neurons. The effect is probably not mediated through adrenal steroids. In addition, ACTH seems to decrease MAP and to increase heart rate through postsynaptic vascular and myocardial effects.

Adrenocorticotropic Hormone↗
PubMed1986

Opioid peptides decrease noradrenaline release and blood pressure in the rabbit at peripheral receptors.

Effects of dynorphin-(1-13), Leu5-enkephalin, D-Ala2,D-Leu5-enkephalin (DADLE), and for comparison bremazocine, on plasma noradrenaline concentration and mean arterial pressure (MAP) were studied in pithed rabbits. In the first series of experiments, the sympathetic outflow was stimulated electrically via the pithing rod at 2 Hz twice for 3 min each (S1, S2). Drugs were administered before S2. Bremazocine 10 micrograms/kg + 2 micrograms/kg/h and 100 micrograms/kg + 20 micrograms/kg/h, dynorphin 1 and 3 micrograms/kg/min, Leu5-enkephalin 100 micrograms/kg/min and DADLE 10 and 30 micrograms/kg/min all diminished the electrically-evoked increase in plasma noradrenaline and MAP. The effects were antagonized by naloxone. In the second series, an infusion of noradrenaline (2 micrograms/kg/min) was given twice for 3 min each (N1, N2). Drugs were administered before N2. Bremazocine 100 micrograms/kg + 20 micrograms/kg/h slightly enhanced the pressor effect of exogenous noradrenaline, whereas dynorphin 3 micrograms/kg/min, Leu5-enkephalin 100 micrograms/kg/min and DADLE 30 micrograms/kg/min caused no significant change. In the third series, the sympathetic outflow was stimulated continuously at 2 Hz, and the interaction of dynorphin and DADLE was studied. Dynorphin 1 microgram/kg/min and DADLE 10 micrograms/kg/min initially decreased MAP to a similar extent. The effect of DADLE faded with time. When, during continuous infusion of DADLE 10 micrograms/kg/min, and after return of MAP to the pre-DADLE level, dynorphin 1 microgram/kg/min or DADLE 10 micrograms/kg/min was infused additionally, the effect of dynorphin was unchanged, whereas that of DADLE was almost abolished. We conclude that the opioid peptides as well as bremazocine decrease action potential-evoked release of noradrenaline and, secondarily, blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Dopamine1 receptor agonist and alpha-2 adrenoceptor antagonist effects of fenoldopam in rabbits.

Neurochemical and circulatory effects of fenoldopam were studied in pithed rabbits with electrically stimulated sympathetic outflow and in strips of the rabbit pulmonary artery. In pithed rabbits, fenoldopam (1-30 micrograms/kg/min) decreased the arterial blood pressure. Fenoldopam (3-30 microgram/kg/min) also increased the norepinephrine spillover rate (the rate at which endogenous norepinephrine enters into the plasma after having been released from postganglionic sympathetic nerves) and decreased the [3H]norepinephrine plasma clearance. The selective dopamine (DA)1 antagonist SCH 23390 (bolus injection of 10 micrograms/kg followed by infusion of 2 micrograms/kg/hr) antagonized markedly and the DA2-selective antagonist domperidone (bolus injection of 200 micrograms/kg followed by infusion of 50 micrograms/kg/hr) antagonized slightly the hypotensive effect. The increase in the norepinephrine spillover rate was enhanced after treatment with desipramine. Clonidine (0.3 microgram/kg/min) reduced the spillover of norepinephrine, and this effect was abolished by fenoldopam (30 micrograms/kg/min). In pulmonary artery strips preincubated with [3H]norepinephrine, fenoldopam (10(-7) and 10(-6) M) increased the electrically evoked overflow of tritium. The effect of fenoldopam (10(-6) M) was prevented in the presence of a supramaximal concentration of clonidine (10(-5) M). The results suggest that fenoldopam lowers blood pressure mainly by activation of vascular smooth muscle DA1 receptors. In addition, however, it blocks prejunctional alpha-2 autoreceptors at postganglionic sympathetic axons.

Adrenergic alpha-Antagonists↗