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At least 685 records · Page 38Linked to original sources
PubMed1996

Coronary vascular effects of dexmedetomidine during reactive hyperemia in the anesthetized dog.

OBJECTIVE: The central sympatholytic effects of alpha2-adrenergic agonists are believed to be beneficial during myocardial ischemia, but the peripheral vasoconstrictive effects are controversial. The aim of this study was to investigate the coronary vascular effects of dexmedetomidine (DM) during reactive hyperemia. DESIGN: The study had a prospective, randomized, open-comparative design. SETTING: University animal laboratory. PARTICIPANTS: Nine mongrel dogs. INTERVENTIONS: Coronary artery occlusions lasting 2 minutes were induced five times at 40-minute intervals. DM, 0.1, 1, and 10 micrograms/kg was administered 15 minutes before the second, third, and fourth coronary occlusion, respectively. The alpha2-antagonist atipamezole was administered before the fifth coronary occlusion. MEASUREMENTS AND MAIN RESULTS: DM, 1 microgram/kg, significantly decreased heart rate (from 128 +/- 13 to 96 +/- 21 beats/min); 10 micrograms/kg of DM also significantly decreased cardiac output (from 3.4 +/- 1.1 to 1.4 +/- 0.4 L/min). DM decreased myocardial blood flow in all layers of normally perfused myocardium. In hyperemic myocardium, DM significantly decreased epicardial blood flow (from 3.30 +/- 1.43 to 1.44 +/- 0.49 mL/min/g after DM 10 micrograms/kg), whereas endocardial blood flow did not change, hereby significantly increasing the endo/epi blood flow ratio (from 0.99 +/- 0.54 to 2.28 +/- 0.78). CONCLUSIONS: In the postischemic hyperemic subendocardial layer, coronary blood flow was preserved after DM. DM reduced primary determinants of myocardial oxygen demand. These effects of DM may be beneficial in conditions of temporary coronary artery occlusion and subsequent reperfusion.

Adrenergic alpha-Agonists↗
PubMed1997

Cardiac disease in chronic uremia: management.

Heart disease is a common cause of morbidity in end-stage renal disease (ESRD) patients. The management of heart disease in these patients requires a multidimensional approach to the management of heart failure, coronary disease, and arrhythmias, and to risk factors such as hypertension, anemia, secondary hyperparathyroidism, and electrolyte/acid-base disturbances. Coronary artery disease management includes use of antianginal drugs and revascularization of coronary arteries with angioplasty +/- stent placement or coronary artery bypass grafting. The long-term outcomes of these procedures need to be assessed and improved. Hypertension occupies a major role in the pathogenesis of heart disease in ESRD, and early and adequate control of hypertension is likely to have a major impact on the progression of cardiac disease. This entails the achievement of optimal volume status, combined with the appropriate use of antihypertensive agents such as calcium channel blockers, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, vasodilators, alpha-blockers, and central sympatholytic drugs. In ESRD patients, specific dialysis-related complications such as intradialytic hypotension and pericardial effusion may have additional effects on cardiac function and require attention. The choice of dialysate composition and membrane may influence clinical outcomes with specific effects on cardiac performance.

Chronic Disease↗
PubMed1995

An unusual case of sympathetically maintained facial pain complicated by telangiectasia.

A 32-year-old woman with a history of maxillary sinusitis, multiple surgical interventions in the maxillary sinus, and a hyperalgesic, erythematous skin lesion in her left infraorbital area, had severe burning pain in the left face. The dermal lesion was diagnosed as atypical telangiectasia and the sinus pathoses determined to be unrelated to her symptoms. Two diagnostic stellate ganglion blocks were performed with concurrent bilateral monitoring of blood flow in the infraorbital skin. Blood flow was significantly increased in the painful erythematous patch although no significant change in flow occurred in the unaffected contralateral skin. The changes correlated to patient's relief from pain. The patient's symptoms were subsequently controlled with an oral sympatholytic agent. This article demonstrates the usefulness of laser doppler flowmetry to establish the diagnosis of sympathetically maintained facial pain despite several confounding conditions and supports the theory that sympathetically maintained pain involves altered function of alpha-1 adrenoreceptors.

Adult↗
PubMed2001

Vagal neurostimulation in patients with coronary artery disease.

We tested the hypotheses that (1) progression of coronary artery disease (CAD) increases sympathetic inflow to the heart, thus impairing cardiac blood supply, and (2) reduced sympathetic tone improves cardiac microcirculation and ameliorates severity of anginal symptoms. Electrical irritation of the nerve auricularis--a sensitive ramus of the vagus nerve--provides a central sympatholytic action. Using this technique, we studied the effects of vagal neurostimulation (VNS) on hemodynamics, the content of atrial noradrenergic nerves and the microcirculatory bed of CAD patients. VNS was performed in the preoperative period of CAD patients with severe angina pectoris. The comparison groups consisted of untreated patients with CAD or Wolff-Parkinson-White syndrome. Atrial tissue of patients with this syndrome (n = 6); with effort angina (n = 14); with angina at rest (n = 10); and with severe angina treated with VNS (n = 8) contained the following volume percentages of noradrenergic nerves: 1.7+/-0.1%, 1.3+/-0.3%, 0.5+/-0.1% (p < 0.05 vs. the other groups) and 1.3+/-0.2%, respectively. In these groups, cardiac microcirculatory vessels (diameter, 10-20 microm) had the following densities: 2.7+/-0.2%, 3.4+/-0.2%, 2.0+/-0.4% (p < 0.05 vs. the other groups) and 3.3+/-0.3%, respectively. VNS treatment abolished angina at rest, decreased heart rate and blood pressure. It improved left ventricular ejection fraction from 50+/-1.5% to 58+/-1.0% (p < 0.05), also changing left ventricular diastolic filling. The ratio of time velocity integrals of the early (Ei) to late (Ai) waves increased from 1.07+/-0.12 to 1.65+/-0.17 after VNS (p < 0.05). In electrocardiograms of VNS-treated patients, QRS- and QT-duration were shortened. the PQ-interval did not change, but T-wave configuration improved. In the postoperative period, heart failure occurred in 90% of the control group. vs. 12% in patients treated with VNS (p < 0.05). We conclude that CAD is characterized by overactivity of sympathetic cardiac tone. Vagal stimulation reduced sympathetic inflow to the heart, seemingly via an inhibition of norepinephrine release from sympathetic nerves. VNS' sympatholytic/vagotonic action dilated cardiac microcirculatory vessels and improved left ventricular contractility in patients with severe CAD.

Angina Pectoris↗
PubMed2002

Intravenous amiodarone modifies autonomic balance and increases baroreflex sensitivity in conscious rats.

Amiodarone is an antiarrhythmic agent commonly used to treat cardiac arrhythmias. This study was designed to investigate the effects of intravenous amiodarone on the neural control of heart rate and arterial pressure and spontaneous baroreflex sensitivity (BRS). Experiments were carried out on conscious freely moving normotensive Wistar (WR) and spontaneously hypertensive rats (SHR). Arterial pressure was continuously monitored before and after amiodarone (50 mg/kg i.v.) or vehicle for 30 min. Heart rate (expressed as the pulse interval, PI) and systolic arterial pressure (SAP) variabilities were assessed using autoregressive spectral analysis. BRS was calculated as the alpha-index (the square root of the ratio between the PI and SAP powers). Amiodarone induced bradycardia and hypotension in both strains, with these effects being more intense in SHR. The variability profile of PI was characterized by a significant reduction of normalized low frequency (LF) and LF/HF ratio, while the high frequency (HF) component both in absolute and normalized units (nu) was increased in both WR and SHR strains. A significant decrease in SAP variance and its LF oscillation was observed. In addition, BRS was also increased in both groups, being more intense in SHR. In both WR and SHR, intravenous amiodarone had a considerable effect on heart rate variabilities (HRV), shifting cardiac sympathovagal balance toward a sympathetic inhibition and/or vagal activation, which were associated with an increase in spontaneous BRS. Decreases of SAP variance and LF(SAP) suggest sympatholytic effects on peripheral vessels. Besides the direct ion channel effects, these changes in the autonomic balance could contribute to the antiarrhythmic action of the intravenous amiodarone.

Amiodarone↗
PubMed2002

Effects of botulinum toxin type A on the superior cervical ganglia in rabbits.

Sympathetic neurolysis is very important in treating chronic pain, especially sympathetically maintained pain. However, conventional neurolytic agents destroy nerve fibers nonselectively and may leave serious complications. Botulinum toxin type A (BTA) selectively acts on cholinergic nerves and inhibits the secretion of acetylcholines (Ach) at the involved nerve endings. Because cholinergic nerves also exist in autonomic ganglia, it is believed that BTA has pharmacological effects on sympathetic ganglia. In this study, after the administration of BTA into the superior cervical ganglion (SCG) in rabbits, the possible clinical use of BTA as a neurolytic agent was evaluated. In the normal saline-treated control group, miosis was not observed in all 12 rabbits. However, in the BTA-treated group, 15 cases of miosis were observed among 40 rabbits (37.5%). Furthermore, BTA induced miosis in a dose-dependent manner, though onset time and duration of miosis varied. Mean time of onset and duration were 1.8 days and 5.3 weeks, respectively. By eosin-hematoxylin (H&E) staining finding, no significant chronological and histological changes between the control and the experimental groups were observed. In conclusion, BTA was found to have a sympathetic ganglion blocking effect over a period of more than 1 month without causing considerable pathologic changes in the SCG, that is, this toxin may be used in the case of sympathetically maintained pain control as a sympatholytic.

Animals↗
PubMed1981

Synthesis and adrenoceptor affinity of some highly polar beta-substituted catecholamines.

In order to assess the potential for sympathomimetic or sympatholytic activity within the series of catecholamine beta-sulfonates 3a-c, alpha- and beta-adrenoceptor binding affinities were determined using rat brain homogenate preparations. Furthermore, their potential for indirect activity was assessed by measurement of blockade of norepinephrine uptake into rat synaptosomal preparations. Activity was uniformly low or nonexistent throughout the series. The possibility of unfavorable solution conformational distribution within the series was investigated by examination of the side chain vicinal 1H NMR coupling constants, but no differences that could account for the lack of affinity were found. The observed behavior may be due to receptor intolerance of the bulky beta-sulfonate substituent or an electronic mismatch in which normal H bonding is significantly altered.

Animals↗
PubMed1981

2-(Isoxazolylethenyl)phenoxypropanolamines: a new class of beta-receptor antagonists with antihypertensive activity.

The synthesis of a series of (E)-1-amino-3-[2-(2-isoxazolylethenyl)phenoxyl-2-propanols is described. These compounds were found to have beta- and alpha-adrenergic blocking properties, as well as hypotensive and antihypertensive properties. The beta-adrenoceptor antagonism of all these compounds was more pronounced than their alpha-sympatholytic and hypotensive activity. 3a was 16 times more potent than labetalol in beta-adrenergic receptor blockade and was effective in lowering blood pressure in acute trials on spontaneously hypertensive rats at a dosage of 15 mg/kg. Structure-activity considerations showed that antihypertensive potency was more sensitive to structural variations than beta-adrenoceptor antagonistic activity. However, in general, those compounds having the most potent beta-adrenoceptor blocking activity also lowered blood pressure most effectively.

Adrenergic alpha-Antagonists↗
PubMed1979

Chemical and biological studies of 1-(2,5-dihydroxy-4-methylphenyl)-2-aminopropane, an analogue of 6-hydroxydopamine.

Autoxidation of the bis(O-demethyl)-p-hydroquinone metabolite of the psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) at pH 7.4 leads exclusively to a bicyclic imino quinone. This imino quinone is a good alkylating agent, forming covalent adducts via 1,4 addition to thiols. The autoxidation appears to be dependent on trace metal catalysis and is dramatically inhibited by components of the 10000g supernatant fraction of rabbit liver homogenates. Incubation of tritium-labeled hydroquinone with bovine serum albumin under oxidizing conditions leads to significant amounts of nonextractable radioactivity which presumably is dependent on imino quinone alkylation of nucleophilic functionalities present on macromolecules. Incubation of tritium-labeled DOM with rabbit microsomes in the presence of NADPH leads to irreversible binding of the label to macromolecular components of the microsomes. Since this binding is NADPH dependent, it is likely that metabolic conversion of DOM to the hydroquinone is involved. The imino quinone oxidation product is highly lypophilic and is capable of crossing the blood-brain barrier. Intravenous administration of tritium-labeled imino quinone to rats resulted in significant nonextractable radioactivity in brain tissue. These properties of the hydroquinone metabolite parallel those reported for the structurally related sympatholytic compound 6-hydroxydopamine and have led to the hypothesis that the psychotomimetic properties of DOM may be mediated through 6-hydroxydopamine-type interactions of the hydroquinone with important macromolecules in the brain.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1977

In vitro O-demethylation of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane.

The possible relationship between metabolism and psychotomimetic activity among the methoxylated 1-phenyl-2-aminopropanes led to our investigation of the in vitro O-demethylation of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (1, DOM, STP). Employing a sensitive and highly selective stable isotope dilution assay, we observed that rabbit liver homogenates biotransform the amine 1 to its 2-O-demethyl, 5-O-demethyl, and bis (O-demethyl) metabolite metabolites. Both monophenolic metabolites are enriched in their S enantiomers. The bis(O-demethyl) metabolite has structural, chemical, and electrochemical similarites to the sympatholytic agent "6-hydroxydopamine". The possible significance of metabolic O-demethylation in terms of the psychotomimetic properties of amine 1 is discussed.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1988

A controlled comparison of thermal biofeedback and relaxation training in the treatment of essential hypertension: II. Effects on cardiovascular reactivity.

In the course of conducting a controlled comparison of progressive muscle relaxation and thermal biofeedback as possible substitutes for second-stage (sympatholytic) antihypertensive medications, we measured reactivity (heart rate, systolic blood pressure, and diastolic blood pressure) to three different stressors (mental arithmetic, cold pressor, and negative mental imagery) before and after treatment and drug withdrawal. Neither treatment was consistently effective in reducing reactivity across a variety of stressors. Relaxation led to more reductions in some aspect of reactivity than did biofeedback. The modest level of reductions in reactivity were seen more for mental arithmetic and systolic blood pressure.

Arousal↗
PubMed1982

Prazosin and propranolol in preoperative management of pheochromocytoma.

Combined use of prazosin and propranolol was effective in preoperative management of three patients with norepinephrine(NE)-secreting pheochromocytoma (PHEO). On admission, all were symptomatic and had moderate to severe hypertension despite treatment with diuretics, propranolol, and sympatholytics. Optimal symptomatic and blood pressure (BP) control was achieved with 6 to 10 mg/day prazosin and 120 to 480 mg/day propranolol every 6 hr in equally divided doses. With this therapy, BP and hematocrit were reduced to levels similar to those found in the postoperative period. The daily urinary excretion of catecholamines and their metabolites was not modified during therapy with prazosin and propranolol. There was a drop in supine systolic (40 to 64 mm Hg) and diastolic (32 to 52 mm Hg) BP in all patients 1 to 2 hr after the first dose of prazosin (1-mg tablet); in two subjects this was accompanied by a larger orthostatic fall (74 and 92 mm Hg systolic; 65 and 78 mm Hg diastolic BP). The high incidence of first-dose effect suggests that a single oral dose of 1 mg of prazosin could aid in the diagnosis of PHEO. The effectiveness of prazosin in controlling the hypertension induced by NE-secreting PHEO suggests that, in man, pressure responses to augmented levels of NE are mediated solely through alpha 1-receptors.

Adolescent↗
PubMed1986

Effect of the calcium channel blocker nitrendipine on left ventricular mass in patients with hypertension.

Reductions in left ventricular (LV) mass have been reported after antihypertensive therapy with certain sympatholytic agents and converting enzyme inhibitors, but little or no improvement has been noted after vasodilator therapy. In this study we evaluated the effect of the calcium channel blocker nitrendipine on echocardiographic LV mass. During a 12-month period, nitrendipine was used as monotherapy in 30 patients and in combination with propranolol or a diuretic in an additional 28 patients. Nitrendipine monotherapy lowered supine blood pressure from 148/97 to 136/83 mm Hg, but LV mass did not change significantly. Supine blood pressure decreased from 155/103 to 134/86 mm Hg in patients receiving combination therapy but, again, changes in LV mass were not significant. These data suggest that nitrendipine is effective in lowering blood pressure, but this is not associated with a significant decrease in LV mass in patients with mild hypertension.

Adult↗
PubMed1989

Effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on hemodynamic control mechanisms.

Dexmedetomidine, a selective alpha 2-adrenoceptor agonist, was administered to five healthy male volunteers in single intravenous doses of 12.5, 25, 50, and 75 micrograms as part of a placebo-controlled study. The drug caused dose-dependent decreases in systolic and diastolic blood pressure. A small initial hypertensive response was observed after injection of the two highest doses. Heart rate was decreased. The concentration of norepinephrine in plasma was decreased significantly (by up to 92%), and the decrease was dose-dependent. No significant drug-induced alterations were observed in plasma renin activity or in the concentrations of atrial natriuretic peptide and arginine vasopressin in plasma. Other drug effects included dose-dependent impairment of vigilance and stimulation of growth hormone secretion. Plasma cortisol levels were unaffected. Dexmedetomidine is a potentially useful tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in human beings and may have therapeutic applications in clinical conditions in which sedative and sympatholytic effects are considered beneficial, such as premedication for anesthesia and surgery.

Adrenergic alpha-Agonists↗
PubMed1986

The sympathetic nervous system in clinical and experimental hypertension.

In summary, many lines of evidence indicate that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals. Patients with established renovascular hypertension have increased sympathetic nervous system activity, as evidenced by increased plasma and urinary norepinephrine levels, elevated excretion of catecholamine metabolites, and an exaggerated depressor response to centrally acting sympatholytic agents. The observation that converting enzyme inhibitors can cause both blood pressure and urinary norepinephrine excretion to return to normal in patients with renovascular hypertension is consistent with the interpretation that activation of the sympathetic nervous system in these subjects is, at least in part, angiotensin-induced. The sympathetic nervous system, via the efferent renal nerves, plays a role in the pathogenesis of hypertension in a number of experimental models. In the spontaneously hypertensive rat of the Okamoto strain (SHR) and in the DOCA/NaCl hypertensive model, increased renal efferent nerve activity contributes to the development of hypertension by causing increased renal sodium retention. In both of these experimental models, renal denervation delays the development and blunts the severity of hypertension. This delay is associated with increased urinary sodium excretion, suggesting a renal efferent mechanism. In contrast to the predominantly efferent renal nerve mechanisms observed in the DOCA-NaCl and SHR models, studies of the effects of renal denervation in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats suggest that renal afferent nerves are important in these models of hypertension. Total renal denervation in rats with established 1K, 1C and 2K, 1C hypertension attenuates the severity of the hypertension without altering sodium intake or excretion, renin activity, water intake, or renal function. Thus, efferent renal nerve activity does not appear to be involved in the development of maintenance of 1K, 1C or 2K, 1C hypertension. In contrast with the findings in SHR and DOCA-NaCl rats, these studies provide indirect evidence that the renal afferent nerves play a role in the pathogenesis of this form of experimental hypertension. The major effect of renal denervation in these models appears to be an interruption of renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Drug Insight: angiotensin-converting-enzyme inhibitors and atrial fibrillation--indications and contraindications.

Large clinical trials have demonstrated that angiotensin-converting-enzyme (ACE) inhibitors are associated with beneficial outcomes in patients with arterial hypertension, heart failure, coronary artery disease, or a combination of these conditions. Other reports have suggested that ACE inhibitors prevent the development or recurrence of atrial fibrillation (AF), a common arrhythmia. In the TRACE trial, in patients with reduced left ventricular function after myocardial infarction, trandolapril reduced the frequency of AF. In the SOLVD trial, a 78% reduction in the frequency of AF after infarction was noted with enalapril compared with placebo. Studies in patients with persistent AF undergoing cardioversion suggest that ACE inhibitors improve outcomes and prevent AF recurrences. The mechanism of AF prevention by ACE inhibitors is unclear, but experimental data show prevention or attenuation of pacing-induced atrial remodeling with ACE inhibitor use. ACE inhibitors decrease angiotensin II concentration; angiotension II stimulates mitogen-activated protein kinases, which in turn activate fibrosis formation and lead to conduction heterogeneity and induction of AF. On the other hand, AF induces atrial dilatation, atrial stretch and atrial secretion of ACE. Among other properties, ACE inhibitors have a sympatholytic effect and increase baroreceptor sensitivity. This review discusses the current data on the use of ACE inhibitors for AF prevention. Although these drugs represent a promising therapeutic option for AF patients, the data so far seem only supportive rather than definitive. Prospective trials are required to validate the benefit of ACE inhibitors and to investigate which patients are most likely to benefit from this pharmacological therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Haemodynamic actions of clonidine in tetraplegia--effects at rest and during urinary bladder stimulation.

We studied the haemodynamic effects of clonidine (2 micrograms/kg/iv) in 7 tetraplegics and 7 normal subjects. Measurements of blood pressure, stroke volume, cardiac output and digital (finger) skin blood flow were made before and after clonidine for 60 minutes. Blood pressure, stroke volume and cardiac output did not fall in tetraplegics, unlike normals. Resting digital skin blood flow was higher in tetraplegics and fell after clonidine. In normal subjects however, an increase in digital skin blood flow occurred after clonidine. The pressor and digital vasoconstrictor responses to bladder stimulation were attenuated after clonidine. The inability of clonidine to induce a fall in blood pressure, stroke volume, cardiac output and cause peripheral vasodilation in tetraplegics is consistent with its central sympatholytic effects. Attenuation of the responses to bladder stimulation suggest an effect on spinal sympathetic neurones.

Adolescent↗
PubMed2007

Selective AT1 receptor antagonism enhances sympathetically mediated vasoconstriction in man.

The vasoconstrictive action of angiotensin II (AII) is partly, sympathetically mediated and angiotensin-converting enzyme (ACE) inhibitors appear to exert a sympatholytic effect. We examine the effect of an orally administered, selective AT(1) receptor antagonist (losartan 50 mg) on sympathetically mediated vasoconstriction in healthy volunteers in an observer blind crossover study. Seven healthy, normotensive volunteers (21-32 years), were studied on two occasions at the end of each 6-week treatment period (losartan or placebo). Forearm blood flow (FABF) (ml/dl forearm/min) was measured by venous occlusion plethysmography during the application of lower body negative pressure (LBNP) (-20 cm H(2)O) and at the end of each incremental infusion of norepinephrine (60, 120, and 240 pmol/min). Comparison of blood flow changes was by repeated measures analysis of variance; P<0.05 was taken as statistically significant. Losartan did not alter blood pressure compared to placebo. It did significantly enhance LBNP-induced vasoconstriction in both the left arm compared to placebo (-36.6+/-3.4 vs -23.5+/-3.3%; P=0.017) and the right arm compared to placebo (-39.5+/-3.8 vs -21.0+/-3.6%; P=0.005). The FABF response to all doses of infused norepinephrine (60, 120, and 240 pmol/min) was also enhanced by losartan compared to placebo (-35.0+/-2.7 vs -18.2+/-6.0%; -43.6+/-4.3 vs -28.6+/-5.8%, and -53.9+/-3.2 vs -42.5+/-6.8%; P=0.057, respectively. Losartan enhances locally mediated sympathetic vasoconstriction in the forearm circulation of man, probably through its effect on circulating AII concentrations and we postulate that the adrenergic sympathetic constrictor action of AII is not mediated by the AT(1) receptor or is surmountable at this receptor.

Adult↗