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At least 55 records · Page 3Linked to original sources
PubMed1981

Influence of sympatholytic drugs on the cardiovascular response to isometric exercise.

1. The effects of single oral doses of various sympatholytic drugs on the heart rate and blood pressure increases during isometric handgrip contraction were studied in six healthy subjects. 2. Bethanidine reduced both the systolic and diastolic increases in pressure. Clonidine reduced the systolic but not the diastolic increase. Oxprenolol alone or in combination with phentolamine or phenyoxybenzamine failed to influence the pressor response. 3. The increase in systemic blood pressure associated with sustained contraction of voluntary muscle appears to be relatively resistant to acute sympathetic adrenoreceptor blockade in man.

Adult↗
PubMed1998

Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole: a pharmacodynamic and kinetic study in healthy volunteers.

BACKGROUND: Specific and selective alpha2-adrenergic drugs are widely exploited in veterinary anesthesiology. Because alpha2-agonists are also being introduced to human practice, the authors studied reversal of a clinically relevant dexmedetomidine dose with atipamezole, an alpha2-antagonist, in healthy persons. METHODS: The study consisted of two parts. In an open dose-finding study (part 1), the intravenous dose of atipamezole to reverse the sedative effects of 2.5 microg/kg of dexmedetomidine given intramuscularly was determined (n = 6). Part 2 was a placebo-controlled, double-blinded, randomized cross-over study in which three doses of atipamezole (15, 50, and 150 microg/kg given intravenously in 2 min) or saline were administered 1 h after dexmedetomidine at 1-week intervals (n = 8). Subjective vigilance and anxiety, psychomotor performance, hemodynamics, and saliva secretion were determined, and plasma catecholamines and serum drug concentrations were measured for 7 h. RESULTS: The mean +/- SD atipamezole dose needed in part 1 was 104+/-44 microg/kg. In part 2, dexmedetomidine induced clear impairments of vigilance and psychomotor performance that were dose dependently reversed by atipamezole (P < 0.001). Complete resolution of sedation was evident after the highest (150 microg/kg) dose, and the degree of vigilance remained high for 7 h. Atipamezole dose dependently reversed the reductions in blood pressure (P < 0.001) and heart rate (P = 0.009). Changes in saliva secretion and plasma catecholamines were similarly biphasic (i.e., they decreased after dexmedetomidine followed by dose-dependent restoration after atipamezole). Plasma norepinephrine levels were, however, increased considerably after the 150 microg/kg dose of atipamezole. The pharmacokinetics of atipamezole were linear, and elimination half-lives for both drugs were approximately 2 h. Atipamezole did not affect the disposition of dexmedetomidine. One person had symptomatic sinus arrest, and another had transient bradycardia approximately 3 h after receiving dexmedetomidine. CONCLUSIONS: The sedative and sympatholytic effects of intramuscular dexmedetomidine were dose dependently antagonized by intravenous atipamezole. The applied infusion rate (75 microg x kg(-1) x min(-1)) for the highest atipamezole dose was, however, too fast, as evident by transient sympathoactivation. Similar elimination half-lives of these two drugs are a clear advantage considering the possible clinical applications.

Adrenergic alpha-Antagonists↗
PubMed2000

Evidence for a sympatholytic effect of mibefradil in the pithed rat preparation.

OBJECTIVE: The T-type prevalent calcium channel blocker mibefradil (MIB) was shown to possess N-type calcium channel blocking properties. As this particular type of calcium channel is known to be crucially involved in the neuronal release of noradrenaline, we have investigated whether MIB could be a sympatholytic drug. METHODS: To evaluate the sympathoinhibitory action, the effects of 3 and 10 micromol/kg MIB on the tachycardic effect of electrical stimulation of the preganglionic cardioaccelerator nerves in the pithed rat were investigated. The effect of MIB on the dose-response curve of externally applied noradrenaline was also studied. To compare the results with a classic L-type calcium channel blocker, the experiments were repeated with 3 and 10 micromol/kg verapamil (VER). RESULTS: The maximal increase in heart rate in response to electrical nerve stimulation was 96 +/- 7 bpm (control, n = 6), 70 +/- 6 bpm (3 micromol/kg MIB, n = 8), 57 +/- 6 bpm (10 micromol/kg MIB, n = 5), 93 +/- 5 bpm (3 micromol/kg VER, n = 6) and 46 +/- 7 bpm (10 micromol/kg VER, n = 5). The tachycardic response to electrical stimulation at 1, 5 and 10 Hz was completely blocked by 5 mg/kg intravenous guanethidine. The maximal increase in heart rate in response to noradrenaline was 96 +/- 4 bpm (control, n = 6), 103 +/- 6 (3 micromol/kg MIB, n = 6), 42 +/- 9 bpm (10 micromol/kg MIB, n = 5), 73 +/- 5 bpm (3 micromol/kg VER, n = 5) and 40 +/- 7 bpm (10 micromol/kg VER, n = 6). Under control conditions and in the presence of 3 micromol/kg MIB and VER the maximal effect of noradrenaline was reached at 0.1 micromol/kg whereas in the presence of 10 micromol/kg MIB and VER it was reached at a dose of 1 micromol/kg. MIB at a dose of 3 micromol/kg was significantly more effective in reducing the chronotropic response to electrical stimulation compared with externally applied noradrenaline. For VER the opposite holds true. These differences were not observed with doses of 10 micromol/kg MIB and VER. CONCLUSION: Mibefradil, besides its direct effect on cardiac T- and L-type calcium channels, reduces the release of noradrenaline from sympathetic nerve endings, most probably by inhibition of presynaptic N-type calcium channels. In the model used this effect is only observable at relatively low concentrations, most probably because of the direct cardiodepressant action of MIB provoked by L-type channel blockade.

Animals↗
PubMed2002

Sympatholytic properties of several AT1-receptor antagonists in the isolated rabbit thoracic aorta.

OBJECTIVE: To evaluate the facilitating effect of angiotensin II on sympathetic neurotransmission to quantitatively compare the sympatho-inhibitory potencies of the selective AT1 -receptor antagonists losartan, irbesartan and telmisartan in the isolated rabbit thoracic aorta. DESIGN: To investigate the influence of pharmacological compounds on pre-junctional sympathetic transmission, the quantification of sympathetic transmitter release is the most straightforward approach. METHODS: To investigate the sympatholytic properties of AT1 -blockers, we studied their effects on the enhancement by angiotensin II of electrical field stimulation (EFS)-evoked (2 Hz) sympathetic transmission in a modified spillover model. RESULTS: Angiotensin II (0.01 nmol/l-0.1 micromol/l) caused a concentration-dependent enhancement of EFS-evoked noradrenaline release (control versus concentrations 0.1 nmol/l-0.1 micromol/l, P<0.05). The maximal augmentation, by almost 100%, was observed at a concentration of 1 nmol/l (FR2/FR1, 2.03 +/- 0.11 versus control, 0.99 +/- 0.03). Higher concentrations (up to 0.1 micromol/l) produced less than maximal facilitation. The AT1 -receptor antagonists losartan (0.1 nmol/l-0.1 micromol/l), telmisartan (0.01-10 nmol/l) and irbesartan (0.1 nmol/l-0.1 micromol/l) concentration dependently attenuated the angiotensin II-mediated (1 nmol/l) enhancement of EFS-evoked sympathetic outflow. The concentrations that reduced the enhancement by 50% (IC50 values, expressed as -log mol/l +/- SEM) were 9.05 +/- 0.16 losartan, 10.28 +/- 0.20 telmisartan and 9.20 +/- 0.23 irbesartan. Accordingly, the order of potency with respect to sympatho-inhibition proved telmisartan> irbesartan = losartan (where > signifies P<0.05). CONCLUSIONS: The facilitating effect of angiotensin II on the sequelae of neuronal stimulation appears to be mediated by pre-synaptically located AT1 -receptors. Facilitation can be concentration dependently attenuated by AT1 -blockade. The order of potency with respect to sympatho-inhibition is telmisartan irbesartan = losartan. These differences may be explained by differences in affinity for the pre-synaptic AT1 -receptor.

Angiotensin II↗
PubMed1990

Omega-conotoxin GVIA, the N-type calcium channel inhibitor, is sympatholytic but not vagolytic: consequences for hemodynamics and autonomic reflexes in conscious rabbits.

We investigated the effects of the N-type calcium channel blocking agent, omega-conotoxin GVIA, on the resting hemodynamics and on some autonomic reflexes in the conscious rabbit. omega-Conotoxin 3 and 10 micrograms/kg i.v. reduced mean arterial blood pressure by 16 +/- 2 and 25 +/- 3 mm Hg, respectively, over 30 min accompanied by a tachycardia. Renal vascular conductance (Doppler flowmeter) increased by 27.6 +/- 3.7 and 38.6 +/- 10.3% at 30 min after omega-conotoxin 3 and 10 micrograms/kg, respectively. Vasodilatation was also observed but to a lesser extent in the hindquarter and mesenteric vascular beds. The baroreceptor-heart rate reflex was evoked by a drug method (bolus injection of sodium nitroprusside and phenylephrine) and by inflation of perivascular balloons implanted on the thoracic vena cava and aorta. omega-Conotoxin (3 micrograms/kg) abolished the sympathetic component of the cardiac baroreceptor reflex without affecting vagal efferent activity. In addition, marked vagal-mediated bradycardia from (a) the "Bezold-Jarisch-like" reflex evoked by serotonin (1-10 micrograms/kg i.v.) and (b) the nasopharyngeal reflex evoked by cigarette smoke were unaffected by omega-conotoxin (3-10 micrograms/kg). We conclude that omega-conotoxin-induced N-type calcium channel blockade abolishes sympathetic but not vagal cardiac efferent activity. The hypotension and peripheral vasodilatation are probably due to the prejunctional sympatholytic action of the peptide. These N-type calcium channels are thus limited to the sympathetic varicosities in the rabbit.

Analysis of Variance↗
PubMedDate not supplied

The effects of sympatholytic drugs on the cardiovascular response to tilting in anaesthetized cats.

1. Using cats anaesthetized with chloralose and urethane, comparison was made of the abilities of several antihypertensive and sympatholytic drugs to lower systemic blood pressure, and to depress the compensatory cardiovascular responses to bilateral carotid occlusion and to 45 degrees head-up tilting. Similar comparisons were also made of the effects of these drugs on the perfusion pressure of the vascularly isolated autoperfused hindquarters, and the response of this to carotid occlusion and tilting. The effects of bilateral vagotomy and haemorrhage on these responses were also studied. 2. It was found that hypotensive doses of both bretylium and guanethidine (3.0 mg/kg, i.v.) markedly depressed the ability of cats to restore their systemic blood pressure and to constrict their hindquarters vasculature during tilting. Both drugs depressed the carotid occlusion reflex in the systemic, but not in the hindquarters, circulation. Neither propranolol, 2.0 mg/kg, i.v., nor bilaterial vagotomy had any effect on these parameters and haemorrhage sufficient to cause marked hypotension was without effect on the systemic responses to carotid occlusion or tilting. 3. Clonidine (1.0, 5.0 and 25 microgram/kg, i.v.), xylazine (62.5, 125 and 250 microgram/kg, i.v.) and reserpine (0.5 and 2.0 mg/kg, i.v.) all caused considerable hypotension but had no effect on the response to tilting of the systemic circulation, apart from somewhat prolonging recovering time. The highest dose of clonidine moderately depressed the hindquarters perfusion pressure, and the response of this to tilting. 4. Clonidine (5.0 and 25 microgram/kg, i.v.) and xylazine (125 and 250 microgram/kg, i.v.) depressed the systemic pressor responses elicited by the ganglion stimulants DMPP and McN-A-343. This may indicate that the ability of clonidine to prolong the pressure recovery during tilt may be due to impaired peripheral sympathetic transmission. 5. It is concluded that drugs which significantly reduce the compensatory pressure reponses to tilting in anaesthetized cats may also cause postural disturbances in man, whilst drugs which merely prolong the period required for pressure compensation seem much less likely to cause serious clinical impairment of orthostatic reflexes. It appears that the cardiovascular response to bilateral carotid occlusion may not provide a good index of the integrity of orthostatic reflexes.

Animals↗
PubMed1995

Sympatholytic action of intravenous amiodarone in the rat heart.

BACKGROUND: Amiodarone is a commonly used antiarrhythmic agent with complex pharmacological effects. Although ventricular arrhythmias can be suppressed soon after intravenous amiodarone, the mechanisms responsible for this action are unclear. We studied the effects of acute treatment with amiodarone on the metabolism and release of norepinephrine (NE) in intact rats and in perfused rat hearts. METHODS AND RESULTS: Experiments were performed in anesthetized rats and in perfused, innervated hearts with amiodarone administered intravascularly. NE release was induced by electrical stimulation of the sympathetic ganglion. Concentrations of NE and its intraneuronal metabolite dihydroxyphenylglycol (DHPG) in hearts, plasma, and coronary venous effluent were measured by high-performance liquid chromatography. Acute administration of amiodarone induced dose-dependent increases in DHPG concentrations in plasma (5 mg/kg, +48%; 15 mg/kg, +84%; and 50 mg/kg, +467%) and in coronary venous effluent (1 mumol/L, +37%; 3 mumol/L, +510%; and 10 mumol/L, +1100%) together with an unchanged basal overflow of NE. In perfused hearts, NE release evoked by nerve stimulation was inhibited by infusion of amiodarone (1 mumol/L, -16%; 3 mumol/L, -24%; and 10 mumol/L, -64%) or by intravenous amiodarone (50 mg/kg) given 1 hour before heart perfusion (-70%), and the extent of this suppression correlated well with levels of DHPG overflow present immediately before nerve stimulation. When given in vitro and in vivo, amiodarone also significantly reduced NE and increased DHPG content in the heart, leading to a raised DHPG/NE ratio. All these effects of amiodarone were similar to those found with reserpine but less potent. In contrast, oral amiodarone produced none of these effects. CONCLUSIONS: Acute administration of amiodarone in perfused hearts or intact rats induces partial NE depletion in the heart by interfering with vesicular NE storage and enhancing intraneuronal NE metabolism, effects associated with an impaired NE release during sympathetic activation. Oral dosing with amiodarone has no such effect. Further study is required to test whether this novel sympatholytic effect of amiodarone contributes to its antiarrhythmic action after intravenous administration.

Administration, Oral↗
PubMed1988

Side effects of sympatholytic antihypertensive drugs.

Antihypertensive drugs with pharmacological action due to sympatholytic activity have been second only to diuretics in their use and efficacy in normalizing blood pressure. Their pharmacological actions have resulted in the notable absence of chemical toxicity, but because of symptomatic side effects, their use has been limited relative to some of the newer antihypertensive agents. Most prominent among undesirable side effects are the central nervous system findings of sedation, altered thought process, depression, and orthostatic or exercise hypotension. Sexual problems, especially in men, are also prominent. Special toxicity is discussed with reference to methyldopa, clonidine, monoamine oxidase inhibitors, and metyrosine.

Female↗
PubMedDate not supplied

[The effect of sympatholytics and adrenergic receptor blockade on the histophysiology of the insular apparatus of the pancreas and insulin sensitivity of white rats].

Experiments were conducted on 200 male albino rats. It was shown that prolonged administration of sympatholytics (ornide or actadine) and also of a blocker of the alpha-adrenorecptors with phentholamine or of beta-adrenoreceptors with inderal led to the accumulation of zinc in the cytoplasm of beta-cells, reduction of the content in them of specific aldehyde-fuchsinophilic granularity, neoformation of the islands of Langerhans and to increase in the animal sensitivity to the exogenous insulin.

Animals↗
PubMed1975

Effects of sympatholytic agents on amanita phalloides toxicity in the rat.

Some sympatholytic agents have been tested for the ability to counteract either the hepatotoxic or the lethal effect of A. phalloides in rats. Propranolol displayed a marked preventive action on the liver damage induced by the poison, but only a moderate influence on the lethality. Reserpine was uneffective in terms of liver derangement, but exerted some protection against the general toxic effect of A. phalloides. Other alpha- or beta-adrenolytic compounds failed to afford any significant protection with respect to both liver injury and lethality. It is suggested that propranolol might interfere with transport or binding of phallotoxins to the liver.

Acid Phosphatase↗
PubMed1977

[Use of preparations with sympatholytic activity for prevention and treatment of postoperative intestinal paresis].

For prophylaxis and treatment of postoperative intestinal paresis the authors employed in 1059 patients gangliolytics and drugs of sympatholytic action -- benzohexonium, aminazine, pyrroxane. An early sympathetic blockade after abdominal surgery was found to be effective both with respect to the prophylaxis of intestinal paresis and in treatment of grave functional disturbances of enteric motility, that develop in different abdominal complications.

Adrenergic alpha-Antagonists↗
PubMed1991

Sympatholytic drugs and cardiac remodelling in human and experimental arterial hypertension.

Perfusion of isoprenaline in the dog may induce left ventricular hypertrophy (LVH), and this effect is suppressed by propranolol. Cultured foetal cardiomyocytes exposed to catecholamines show an increase in protein synthesis and RNA turnover. In spontaneously hypertensive rats (SHR), and perhaps in man, sympatholytic agents appear to be more effective in preventing or reversing LVH than some other antihypertensive drugs. These data suggest that, if increased load remains the main trigger mechanism for cardiac remodelling in arterial hypertension, the sympathetic nerve activity may modulate the response of the cardiac cells.

Animals↗
PubMed1991

Use of centrally acting sympatholytic agents in the management of hypertension.

Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction.

Aged↗
PubMed1988

The influence of sympathomimetic and sympatholytic agents on the salivary flow rate and concentration of Ca, P and protein in the parotid gland of the goat.

1. The role of the sympathetic autonomic division on the parotid gland of normal and thyroparathyroidectomized (t.x.p.t.x.) goats was studied. 2. The salivary flow rate and concentration of Ca, P and protein was tested during the intravenous infusions of sympathomimetic and sympatholytic agents. 3. The intravenous infusion of isoprenaline modified the salivary flow rate and the concentration of total protein. 4. None of the tested drugs modified significantly the concentration of Ca and P in the parotid saliva. 5. The results obtained in normal and t.x.p.t.x animals were similar; it seems that PTH is not involved in the observed changes.

Animals↗
PubMed1977

[Sympathomimetic and sympatholytic drugs in the therapy of glaucoma (author's transl)].

The basis of sympathetic impulse transmission are summarised. Sympathomimetics and sympatholytics are discussed with regard to their mode of action, clinical use and contra-indications. We found that a 1% solution of adrenaline twice a day together with miotics is most suitable for long-term treatment. With the beta-blockers Bupranolol and Timolol tried by us can a massive pressure reduction be obtained, but which is of short duration with the concentrations used up till now. Adrenergic potentiators can not be recommended.

Albuterol↗
PubMed1984

Evidence for a peripheral component in the sympatholytic actions of clonidine and guanfacine in man.

The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, cross-over study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36 +/- 14% after clonidine (p less than 0.05) and by 32 +/- 11% (p less than 0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0 +/- 4.7 lU/ml (p less than 0.05) after clonidine and 14.7 +/- 11.5 lU/ml (p less than 0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these alpha 2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.

Adult↗
PubMed1979

[Hemodynamic and humoral changes during administration of a sympathomimetic and a sympatholytic drug with special notes on the regulation of renin release (author's transl)].

Studies in normal volunteers documented the positive inotropic effects of Etilefrin-HCL, a direct sympathomimetic drug, with increases of systolic blood pressure, renal blood flow and glomerular filtration rate. Sodium and potassium excretion as well as serum potassium decreased. After an additional injection of Metoprolol, a beta 1-sympatholytic drug, blood pressure, renal blood flow and glomerular filtration rate normalized, whereas electrolyte excretion decreased further. Renin release was decreased during administration of Etilefrin as well as during combined Etilefrin and Metoprolol application. Reziprocal to changes of blood pressure, plasma norepinephrine concentration decreased during Etilefrin and increased during combined administration of Etilefrin and Metoprolol. The results lead to the following interpretation: Changes of blood pressure and renal hemodynamics are mediated by beta 1-adrenergic effects of Etilefrin, whereas the electrolyte excretion is influenced by beta 2-adrenergic effects. Renin release seems to be influenced by beta 1 as well as beta 2-adrenergic receptors.

Adult↗
PubMed1992

Comparison of peripheral and central nervous system sympatholytic actions of prazosin using the cat nictitating membrane.

Prazosin is a highly selective alpha 1-adrenoceptor antagonist that decreases blood pressure by actions on both the peripheral and central (CNS) divisions of the nervous system. The present investigation was undertaken in an attempt to characterize the relative contribution of these two sympatholytic sites of action. Submaximal contractions of the nictitating membranes were evoked by electrical stimulation of the preganglionic cervical sympathetic nerve trunk and by stimulation of the posterior hypothalamus in anesthetized cats. In initial control experiments, phenoxybenzamine (0.1-3.0 mg/kg i.v.) produced an equivalent depression of evoked nictitating membrane responses from both peripheral and CNS sites of activation which suggests only a peripheral blocking action as well as functional equivalence of the intensity of CNS and peripheral nerve stimulation. In contrast, prazosin (3-300 micrograms/kg i.v.) caused a differential dose-related depression of the evoked responses with ED50s of 81.5 micrograms/kg (peripheral stimulation) and 12.5 micrograms/kg (CNS stimulation) respectively; P less than 0.05. Pretreatment with rauwolscine (500 micrograms/kg i.v.) totally prevented the differential CNS sympatho-inhibition produced by prazosin. These results indicate that, although both CNS and peripheral sites of drug action are manifest, the ED50 for prazosin-induced CNS sympatho-inhibition is approximately 6-fold less than that required for direct alpha 1-adrenoceptor blockade at the end organ. In addition, prazosin produces CNS sympatho-inhibition indirectly by means of an alpha 2-adrenoceptor mechanism.

Anesthesia↗