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PubMed2001

Endothelin-A receptor antagonist inhibits angiotensin II and noradrenaline in man.

AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor produced by the vascular endothelium. The interactions of ET with the mediators of the sympathetic nervous system and the renin-angiotensin-system in humans are unclear. METHODS: We studied the effects of the ETA-selective antagonist BQ-123 and the ETB-selective antagonist BQ-788 (both 10(-10)-10(-8) M) on ET-1 (10(-16)-10(-10) M), angiotensin II (AT, 10(-16)-10(-10) M) and noradrenaline (NA, 10(-16)-10(-10) M) induced vasoconstriction in the human skin microcirculation in vivo in 25 healthy male volunteers using laser Doppler flowmetry and double injection technique. RESULTS: BQ-123 caused a dose-dependent vasodilatation (maximum effect: + 949 +/- 84 AUC-PU, P < 0.001), whereas BQ-788 induced mild vasoconstriction (maximum effect: -388 +/- 96 AUC-PU, P < 0.01). In the presence of BQ-123, but not BQ-788, ET-1, AT and NA caused markedly less vasoconstriction at any tested agonist dose; the effect was most pronounced on ET-1 (maximum effect at 10(-14) M: + 814 +/- 93 AUC-PU vs ET alone, P < 0.001), followed by noradrenaline (maximum effect at 10(-16) M: +580 +/- 107 AUC-PU vs NA alone, P < 0.01) and angiotensin II (maximum effect at 10(-14) M: + 493 +/- 111 AUC-PU vs AT alone, P < 0.001). CONCLUSIONS: ETA-selective antagonism inhibits vasoconstriction to AT and NA in vivo in healthy subjects. This beneficial effect may be useful for the treatment of patients with cardiovascular disease including hypertension especially in combination therapy with sympatholytic agents and inhibitors of the renin-angiotensin system.

Adult↗
PubMed2003

The activity of single vasoconstrictor nerve units in hypertension.

AIM: It has long been established from controlled experiments in anaesthetized animals that it is more accurate to quantify the mean frequency of efferent sympathetic nerve activity from single unit than from multi-unit bursts recordings. More recently, sympathetic nerve hyperactivity has been reported in patients with essential hypertension (EHT) when using microneurographic recordings from peripheral efferent nerves. This review will focus on the mean frequency of single unit of muscle sympathetic nerve activity (s-MSNA) in relation to that of multi-unit bursts (MSNA) as obtained by microneurography in EHT. RESULTS: We have shown that the resting levels of s-MSNA and MSNA were increased in uncomplicated EHT, white coat hypertension and in EHT complicated by left ventricular hypertrophy. There was a relatively greater increase in s-MSNA than in MSNA in mild hypertension and in complicated EHT. We also found that both s-MSNA and MSNA were increased to a similar extent in conditions known to affect reflexes emanating from the heart and influencing sympathetic output, such as acute myocardial infarction. In other preliminary studies, the increase of s-MSNA in response to the discomfort of cold pressor test was greater than that of MSNA and this difference was abolished by the centrally sympatholytic agent moxonidine. CONCLUSION: These results are consistent with the hypothesis that an increase in the mean frequency of central sympathetic discharge to the periphery (greater s-MSNA than MSNA) is involved in the pathogenesis and complications of EHT. Target organ damage may in turn lead to an increase in overall sympathetic output (excessive MSNA increase) through the operation of peripheral reflex mechanisms.

Animals↗
PubMed1998

Comparison of the effects of moclobemide and selegiline on tyramine-evoked mydriasis in man.

AIMS: To examine the feasibility of using the human iris in vivo for the assessment of the interaction between tyramine and monoamine oxidase (MAO) inhibitors. To examine the relative roles of the two forms of MAO in terminating the response to sympathomimetic amines in the iris, by comparing the effects of single oral doses of moclobemide, a selective MAO-A inhibitor, and selegiline, a selective MAO-B inhibitor, on mydriatic responses to tyramine. METHODS: Twelve healthy male volunteers participated in three monthly sessions, each associated with ingestion of one capsule (moclobemide 450 mg, selegiline 10 mg, or placebo), according to a double-blind, balanced, cross-over design. Tyramine hydrochloride eye-drops (75 mM, 2 x 10 microl) were instilled three times in the left conjuctival sac at 40 min intervals. Pupil diameter was monitored with a binocular infrared television pupillometer before and for 4.5 h after ingestion of the capsule. The pupillary response to tyramine was expressed as the area under the pupil diameter x time curve (arbitrary units). A blood sample was taken before and 2 h after ingestion of the capsule, for the assay of platelet MAO-B activity, and plasma 3,4-dihydroxyphenylglycol (DHPG) concentration, an index of MAO-A activity. Platelet MAO activity was assayed radiochemically, using [14C]-phenylethylamine as substrate, and plasma DHPG by high performance liquid chromatography (h.p.l.c.). The results were analysed using analysis of variance with repeated measures, followed by Bonferroni's corrected t-test, using a significance criterion of P < 0.05. RESULTS: Both moclobemide and selegiline, compared with placebo, caused significant miosis in the right (untreated) eye. The changes in pupil diameter (mm +/- s.e. mean) from the pretreatment measurement were: placebo -0.09 +/- 0.07, moclobemide -0.52 +/- 0.09, selegiline -0.26 +/- 0.1. The mydriatic response to tyramine was potentiated by moclobemide, compared with the response recorded in the presence of placebo. The responses to tyramine (arbitrary units +/- s.e. mean) were: placebo 77.08 +/- 11.65, moclobemide 140.25 +/- 18.9, selegiline 72.75 +/- 12.35. Both moclobemide and selegiline significantly reduced platelet MAO activity, compared with placebo. The changes in platelet MAO activity (nmol h(-1) mg(-1) protein +/- s.e. mean) from the pretreatment level were: placebo 0.5 +/- 0.62, moclobemide -6.7 +/- 0.66, selegiline -17.7 +/- 0.87. Moclobemide significantly reduced plasma DHPG concentration, compared with placebo. The changes in plasma DHPG concentration (nmol l(-1) +/- s.e. mean) from the pretreatment level were: placebo -0.01 +/- 0.24, moclobemide -4.98 +/- 0.32, selegiline -0.51 +/- 0.26. CONCLUSIONS: The potentiation of tyramine-evoked mydriasis by moclobemide is likely to reflect the inhibition of MAO-A activity in the iris, consistent with the activity of this enzyme in sympathetic nerve terminals. The lack of effect of selegiline on tyramine-evoked mydriasis argues against a role of MAO-B in terminating the effects of sympathomimetic amines in the iris. The effects of the two drugs on platelet MAO activity and plasma DHPG concentration are in agreement with previous reports and consistent with the relative selectivity of moclobemide for MAO-A and of selegiline for MAO-B. The miosis caused by the two MAO inhibitors is likely to be due to a central sympatholytic action of the drugs.

Adult↗
PubMed2001

Magnesium as part of balanced general anaesthesia with propofol, remifentanil and mivacurium: a double-blind, randomized prospective study in 50 patients.

BACKGROUND AND OBJECTIVE: To test the hypothesis that magnesium sulphate reduces the amount of remifentanil needed for general anaesthesia in combination with propofol and mivacurium, we studied 50 patients undergoing elective pars plana vitrectomy in a double-blind, randomized prospective fashion. METHODS: Magnesium sulphate (50 mg kg(-1) body weight) or placebo (equal volume of NaCl) was given slowly intravenously after induction of anaesthesia with propofol 1-2 mg kg(-1). Anaesthesia was maintained with propofol (using electroencephalographic control), mivacurium (according to train-of-four monitoring of neuromuscular blockade) and remifentanil (according to heart rate and arterial pressure). RESULTS: We observed a significant reduction in remifentanil consumption from 0.14 to 0.09 microg kg(-1) min(-1) (P < 0.01). Mivacurium consumption was also markedly reduced from 0.01 to 0.008 mg kg(-1) min(-1) (P < 0.01), whereas propofol consumption remained unchanged. There was a trend towards lower postoperative pain scores, less pain medication requirements in 24 h after surgery and less postoperative nausea and vomiting in the magnesium group but not statistically significant. No side-effects were observed. CONCLUSION: We can recommend the use of magnesium sulphate as a safe and cost-effective supplement to a general anaesthetic regimen with propofol, remifentanil and mivacurium, although we cannot clearly distinguish between a mechanism as a (co)analgesic agent at the NMDA-receptor site or its properties as a sympatholytic. The effect of a single bolus dose of 50 mg kg(-1) on induction lasts for about 2 h. For longer cases, either a continuous infusion or repeated bolus doses might be necessary.

Adult↗
PubMedDate not supplied

Cardiac glycosides in the next millennium.

Despite the documented efficacy of cardiac glycosides in improving symptoms in patients with heart failure caused by systolic ventricular dysfunction, considerable debate continues as to whether the use of this class of drugs should continue into the next millennium. In this review, the authors briefly examine the basic pharmacology of these drugs relevant to the treatment of heart failure, emphasizing their role in reducing sympathetic nervous system activity in patients with advanced heart failure. Next, withdrawal trials and the Digoxin Investigation Group dataset are reviewed in some detail. Despite these important additional data on the safety and efficacy of digitalis use in heart failure that became available in the 1990s, considerable controversy remains. Perhaps most importantly, if the mechanism by which these drugs improve symptoms in patients with heart failure is principally mediated by sympatholytic activity, do they remain relevant as beta-adrenergic antagonists become standard therapy for this disease?

Cardiac Glycosides↗
PubMed2001

Both right and left cervical cordotomies depress sympathetic indexes derived from heart rate variability in humans.

Unilateral percutaneous cervical cordotomy, performed in humans to relieve intractable cancer pain, elicits signs of ipsilateral sympathetic block. In patients undergoing right or left percutaneous cervical cordotomy (9 per group), changes in sympathovagal balance were evaluated by spectral analysis of heart rate to confirm the sympatholytic effect of this surgical procedure and to investigate the lateralization of sympathetic cardiac control. For these purposes, heart rate variability was recorded 1 hour before cordotomy and 24 hours later. Cordotomy significantly depressed the low frequency peak (LF) of heart rate variability and increased the high frequency component (HF), when measured as a percentage of total power. As a consequence, the LF/HF ratio decreased significantly (P =.001), particularly during standing. The effects of right or left cordotomies were not significantly different. In conclusion, in humans unilateral percutaneous cervical cordotomy depresses some sympathetic indexes (LF/total power ratio and LF/HF ratio) derived from heart rate variability, irrespective of side.

Adult↗
PubMed2004

Effects of moxonidine vs. metoprolol on blood pressure and metabolic control in hypertensive subjects with type 2 diabetes.

Subjects with type 2 diabetes experience an increased cardiovascular morbidity and mortality, related to a high prevalence of hypertension, dyslipidemia, and obesity. Antihypertensive treatment with beta-adrenergic receptor blockers may have deleterious metabolic consequences, including worsening of lipid profiles and insulin sensitivity. The centrally-acting sympatholytic agent moxonidine may improve these variables. In this randomised, double-blind multicenter study, the effects of two widely used antihypertensive agents--moxonidine (MOX) and the beta (1)-selective adrenergic receptor blocker metoprolol (MET)--on blood pressure and metabolic control were directly compared in hypertensive subjects with type 2 diabetes. Patients received either MOX (0.2 - 0.6 mg/d) or MET (50 - 150 mg/d) for 12 weeks, intending comparable blood pressure control. In total 200 patients were randomized. Here we report results from the per protocol population consisting of 127 patients (MOX 66, MET 61) but similar results were found in the ITT population. Reductions in systolic (SBP) and diastolic (DBP) blood pressures after 12 weeks were similar in both groups: In the MOX group, mean SBP (+/- SD) decreased from 154 +/- 12 to 142 +/- 17 mmHg and mean DBP from 91 +/- 9 to 83 +/- 9 mmHg. In the MET group, mean SBP decreased from 152 +/- 13 to 140 +/- 15 mmHg, and mean DBP from 90 +/- 8 to 84 +/- 10 mmHg. Mean HbA (1C) values did not differ between groups after 12 weeks (MOX 8.1 +/- 1.4 Hb%, MET 8.1 +/- 1.5 Hb%, intention-to-treat population). However, fasting plasma glucose decreased in the MOX group (median change - 5 mg/dl), but increased in the MET group (+ 16 mg/dl; p < 0.05). Median changes in the insulin resistance index (HOMA (IR)) were + 0.56 micro IU x mol/L (2) in the MET group, and - 0.27 micro IU x mol/L (2) in the MOX group. Correspondingly, fasting triglycerides increased with a median change of + 29.5 mg/dL in the MET group, but decreased in the MOX group (- 27.5 mg/dl; p < 0.05). These results indicate that MOX, unlike MET, may elicit beneficial adaptations in glucose and lipid metabolism in hypertensive subjects with type 2 diabetes, although mean HbA (1c) values did not differ. In long-term treatment in this high-risk population, MOX thus may decrease global vascular disease risk to a greater extent than MET.

Adult↗
PubMed2005

[Acute treatment of stable hemodynamically tolerable ventricular tachycardia].

Sustained monomorphic ventricular tachycardia is a potentially life-threatening ventricular tachycardia. The arrhythmia can be treated with antiarrhythmic drugs, when the patient is hemodynamically stable. Class IC antiarrhythmic drugs like flecainide and propafenon or ajmaline (class IA/IC) are very effective. The use of lidocaine is obsolete. Sotalol is also effective, however, caution is advised because of its significant beta-sympatholytic properties. Amiodaron is frequently used, although it has never been studied in the setting of stable ventricular tachycardia. Earlier studies have demonstrated that it is effective in the treatment of recurrent, hemodynamically unstable ventricular tachycardia. When a particular drug does not terminate tachycardia, further drugs should not be given. Electrical cardioversion is preferred.

Anti-Arrhythmia Agents↗
PubMed1993

[Alpha 2-agonists in anesthesia and intensive medicine].

The neurotransmitters adrenaline and noradrenaline are non-selective adrenergic agonists which interact with both subtypes of alpha- and beta-receptors. Clonidine, an alpha 2-adrenergic drug with a selectivity ratio of 200/1 for alpha 2/alpha 1 has been used in clinical practice for more than 20 years. Although alpha 2-agonists have vasoconstrictor properties, sympatholytic effects on the central nervous system predominate. As a result, the sympathetic outflow from the medullary pressor centres is decreased mediating the hypotensive effects of the alpha 2-agonists. These compounds also exhibit sedative, anxiolytic, analgesic, and haemodynamic stabilising properties. The identification of alpha 2-adrenoceptors has yielded information on their biochemical properties, signal transduction, modulation of the sympathetic nervous system and neurotransmission. The classification of alpha 2-receptors based on anatomical locations and identified as presynaptic alpha 2-receptors and postsynaptic alpha 1-receptors proved to be untenable after postsynaptic and extrasynaptic alpha 2-receptor locations had been identified. At least 3 isoreceptors which are heterologously distributed in the brain have been identified. Guanine nucleotide proteins (G proteins) couple the receptor to an effector mechanism (i.e. intracellular messenger cascade, ion channel). More selective for the alpha 2-adrenoceptor than clonidine is dexmedetomidine (1600/1 of alpha 2/alpha 1), a very potent agonist at the alpha 2-adrenoceptor. Imidazole derivatives (like clonidine and dexmedetomidine) also bind to other nonadrenergic receptors ("imidazoline receptors") which may produce some effects (i.e. vagotonia) previously ascribed to alpha 2-adrenoceptors. alpha 2-receptors exist in brain tissue and several peripheral organs and tissues including the liver, eye, kidney, pancreas and platelets. Anaesthetic interest has focussed on reductions in anaesthetic requirements since experimental and clinical studies have shown that alpha 2-agonists expert powerful analgesic and anaesthetic effects. The hypnotic response is probably mediated by activation of alpha 2-adrenoceptors in the locus coeruleus. Analgesia is induced by modulation of the nociceptive pathway at the level of the dorsal root neuron and other sites not yet unambiguously characterised. Dexmedetomidine reduces the anaesthetic requirements for halothane by more than 90%. Cerebral blood flow and intraocular pressure are reduced by alpha 2-agonists. Epidural, intrathecal, intravenous and transdermal application of clonidine resulted in pain reduction, during and following surgery and in patients with neurogenic or otherwise intractable cancer pain. Administration of alpha 2-agonists induces only minor respiratory effects. Salivary flow is reduced by alpha 2-agonists and gastric and small-bowel motility is decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗
PubMed1993

[Neurolytic block of the lumbar sympathetic trunk in advanced stages of peripheral arterial occlusive disease].

UNLABELLED: Neurolytic blocks of the lumbar sympathetic trunk enable a less invasive sympathetic denervation if compared to standard surgical procedures. METHODS: 34 patients undergoing chemical lumbar sympathectomy (CLS) for advanced arterial occlusive disease were prospectively studied. An actual indication for reconstructive vascular surgical intervention had been excluded in all patients. The sympatholytic efficacy, different haemodynamic variables, the relief of rest pain and the effect on ischaemic ulcers were quantified before, 3 and 21 days after CLS. RESULTS: The mean intensity of rest pain, as assessed on a visual analogue scale (0-100 mm), significantly decreased from 60 mm to 31 and 34 mm, respectively. 9 of 12 patients with ischaemic ulcers showed partial or complete remission within the study period. Overall, in 88% of patients sympathetic denervation could be demonstrated by ablation of the sympatho-galvanic skin response. The mean difference in skin temperature between the treated and the untreated leg significantly increased from -0.73 degrees C to +0.34 and +0.39 degrees C, respectively. Doppler-sonographic measurements of the ankle-pressure-index showed a minor increase from 0.34 to 0.36 and 0.42; however, these changes did not reach significance. Neither changes of the different physiologic variables nor data of the patient history could predict the relief of rest pain after CLS. The only side effect of CLS was transient neuralgia of the genitofemoral nerve occurring in 19% of patients. CONCLUSION: Considering the relatively short follow-up period, the results of this study support evidence of the therapeutic efficacy of CLS for rest pain and ischaemic ulcers in patients with advanced arterial disease. The prognostic value of standard variables for estimation of sympathetic reactivity and skin blood flow, however, could not be confirmed.

Aged↗
PubMed1988

[Postoperative disorder of bladder emptying in gynecology: pathophysiology and possibilities for treatment].

Urinary retention after radical hysterectomy is due to partial or complete denervation of the bladder and proximal urethra which is dependent on surgical radicality. In contrast, incomplete bladder emptying after surgery for stress induced urinary incontinence, has its origin in an infravesicular functional obstruction and is dependent on the operation performed. The use of drugs (alpha-sympatholytics, parasympathomimetics) seem to be of limited value, especially after stress-incontinence surgery. Preoperative information, perioperative supra pubic bladder drainage, postoperative bladder training and in rare cases intermittent self-catheterisation and transurethral surgery are the key factors in successful treatment of postoperative urinary retention.

Female↗
PubMed1983

[Ptosis in the differential diagnosis of neurologic diseases].

This review summarizes those neurological diseases which are accompanied by a drooping of the upper lid, due to weakness of the m. levator palpebrae or m. tarsalis respectively. After connatal ptosis with or without involvement of other bulbar muscles the different types of muscular dystrophies are mentioned. Myositis, disturbances of potassium regulation and myasthenia gravis are other causes of ptosis. Diseases involving the oculomotor nerve (aneurysm, upper herniation, cavernous sinus thrombosis, orbital cavity processes, superior orbital fissure syndrome) may lead to associated ptosis. Metabolic disturbances, such as diabetes mellitus, Wernicke's encephalopathy and botulism may be accompanied by ptosis. Infectious diseases such as polyneuritis, meningitis or encephalitis can lead to ptosis. Sympatholytic ptosis is due to diseases of the central or peripheral course of the sympathetic nerve from the diencephalon via the cervical medulla, the neck, internal carotid artery to the superior orbital fissure. This type of ptosis is usually accompanied by miosis and often by sweating loss on the same side.

Blepharoptosis↗
PubMed1981

[Clinidine-induced bradycardia: studies of the effect on the human sinus node (author's transl)].

Heart rate, atrioventricular conduction, sinus-node recovery time and effectiveness of carotid-sinus massage on heart rate were measured before and every five minutes after intravenous injection of 0.15 mg clonidine (Catapresan) in 11 patients (averaged age 60 years) with symptomatic bradycardia (dizzy spells, syncope, palpitations). Th results indicated the following significant (P less than 0.05) mean maximal effects: heart rate fell by 12% (from 59 to 52/min), capacity of atrioventricular conduction by 9% (from 132 to 121/min), while maximal sinus-node recovery time ("over-drive suppression") doubled (from 1704 to 3562 ms), heart rates of 120, 150 and 200/min being used for diagnostic atrial overdrive stimulation at each five-minute period after clonidine. During clonidine administration three patients developed a so-called hypersensitive carotid sinus reflex, in two patients the effectiveness of carotid sinus massage decreased, in three if increased, while in three it remained normal. It is concluded that (1) during bradycardia, initiated or increased by sympatholytic drugs, tests should be undertaken to exclude latent sinus-node syndrome and (or) hypertensive carotid-sinus reflex; (2) clonidine should not be used in patients with signs of sinus-node dysfunction.

Aged↗
PubMed1981

[Effect of clonidine on plasma-catecholamine levels at rest and on ergometric exercise (author's transl)].

The effect of clonidine on peripheral venous-plasma catecholamine concentration was assessed in ten subjects with normal circulation, at rest and on submaximal bicycle exercise. Three hours after oral intake of 300 micrograms clonidine in single dose there was significant lowering of the plasma adrenaline and noradrenaline levels. Six hours after intake the lowest plasma catecholamine level was reached, but after 24 hours the clonidine effect had largely disappeared. The sympatholytic effect of clonidine was relatively less marked with bicycle exercise than at rest. When clonidine had been given for only a short period at moderate dosage, there was no exaggerated catecholamine rise. Clonidine administration did not effect plasma dopamine levels. These results indicate that clonidine decreases plasma adrenaline and noradrenaline levels without significant effect on circulatory regulation.

Adult↗
PubMed1999

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure.

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Amlodipine↗
PubMed1989

Post-carotid endarterectomy hypertension: association with elevated cranial norepinephrine.

The cause and mechanism of post-carotid endarterectomy hypertension remains unknown. To determine the influence of the sympathetic and renin-angiotensin system, we measured cranial and peripheral plasma levels of catecholamine and renin in patients undergoing carotid endarterectomy. Baseline samples were drawn just before carotid clamping (sample I) and compared with study samples drawn immediately after clamp release (sample II), 2 to 6 hours after surgery (sample III), and then 18 to 24 hours after surgery (sample IV). The patients with post-carotid endarterectomy hypertension had an associated increase of cranial and peripheral norepinephrine levels in the postoperative hypertensive period whereas the patients without post-carotid endarterectomy hypertension did not. This association was most pronounced and statistically significant in cranial samples II (p = 0.032) and III (p = 0.005). Epinephrine and dopamine values did not correlate with post-carotid endarterectomy hypertension. Renin values were higher in cranial than in peripheral samples at time period 2 (p = 0.011), suggestive of a central nervous system Goldblatt phenomenon. However, the renin values did not correlate with post-carotid endarterectomy hypertension. We conclude that post-carotid endarterectomy hypertension is associated with elevated cranial norepinephrine levels, suggestive of a central nervous system sympathomimetic mechanism. Optimal prevention and treatment of this brief but frequently occurring hypertension should include a central-acting sympatholytic agent.

Aged↗
PubMed1997

Substitution of a mutant alpha2a-adrenergic receptor via "hit and run" gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo.

Norepinephrine contributes to antinociceptive, sedative, and sympatholytic responses in vivo, and alpha2 adrenergic receptor (alpha2AR) agonists are used clinically to mimic these effects. Lack of subtype-specific agonists has prevented elucidation of the role that each alpha2AR subtype (alpha2A, alpha2B, and alpha2C) plays in these central effects. Here we demonstrate that alpha2AR agonist-elicited sedative, anesthetic-sparing, and analgesic responses are lost in a mouse line expressing a subtly mutated alpha2AAR, D79N alpha2AAR, created by two-step homologous recombination. These functional changes are accompanied by failure of the D79N alpha2AAR to inhibit voltage-gated Ca2+ currents and spontaneous neuronal firing, a measure of K+ current activation. These results provide definitive evidence that the alpha2AAR subtype is the primary mediator of clinically important central actions of alpha2AR agonists and suggest that the D79N alpha2AAR mouse may serve as a model for exploring other possible alpha2AAR functions in vivo.

Analgesics↗
PubMed2000

Nasal airflow in health and disease.

This review examines our present understanding of the physiology, pathophysiology and pharmacology of nasal airflow. The main aim of the review is to discuss the basic scientific and clinical knowledge that is essential for a proper understanding of the usefulness of measurements of nasal airflow in the clinical practice of rhinology. The review concludes with a discussion of the measurement of nasal airflow to assess the efficacy of surgery in the treatment of nasal obstruction. Areas covered by the review include: influence of nasal blood vessels on nasal airflow; nasal valve and control of nasal airflow; autonomic control of nasal airflow; normal nasal airflow; nasal cycle; central control of nasal airflow; effect of changes in posture on nasal airflow; effect of exercise on nasal airflow; effect of hyperventilation and rebreathing on nasal airflow; nasal airflow in animals; cerebral effects of nasal airflow; sensation of nasal airflow; sympathomimetics and sympatholytics; histamine and antihistamines; bradykinin; and corticosteroids.

Administration, Intranasal↗