Topical application of L-carnosine to skeletal muscle excites the sympathetic nerve innervating the contralateral skeletal muscle in rats.

We previously obtained evidence suggesting that physical exercise increases the release of L-carnosine (CAR) from muscles and that CAR affects autonomic neurotransmission and physiological phenomena in rats. It has also been reported that exercise elicits an increase in activity of the sympathetic nerve innervating the skeletal muscle. Therefore, in this study, we investigated the effect of CAR application, onto the surface of the right femoral muscle, on activity of the sympathetic nerve innervating the left femoral muscle, in urethane-anesthetized rats. Topical application of 10 pg (44.2 fmol) of CAR increased either skeletal muscle sympathetic nerve activity (skeletal muscle-SNA) or skeletal muscle blood flow (skeletal muscle-BF) of the contralateral skeletal muscle. Furthermore, thioperamide, a histamine H3-antagonist, inhibited the increase in skeletal muscle-SNA, and butoxamine, a ß2-antagonist, abolished the increase in skeletal muscle-BF caused by topical application of CAR. The present results suggest that CAR released from muscles during physical exercise might affect skeletal muscle-SNA and skeletal muscle-BF on the opposite side of the body via a CAR evoked effect in muscles.

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na(+) channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC.

Caloric restriction decreases orthostatic tolerance independently from 6° head-down bedrest.

Astronauts consume fewer calories during spaceflight and return to earth with an increased risk of orthostatic intolerance. Whether a caloric deficiency modifies orthostatic responses is not understood. Thus, we determined the effects of a hypocaloric diet (25% caloric restriction) during 6° head down bedrest (an analog of spaceflight) on autonomic neural control during lower body negative pressure (LBNP). Nine healthy young men completed a randomized crossover bedrest study, consisting of four (2 weeks each) interventions (normocaloric bedrest, normocaloric ambulatory, hypocaloric bedrest, hypocaloric ambulatory), each separated by 5 months. Muscle sympathetic nerve activity (MSNA) was recorded at baseline following normocaloric and hypocaloric interventions. Heart rate (HR) and arterial pressure were recorded before, during, and after 3 consecutive stages (7 min each) of LBNP (-15, -30, -45 mmHg). Caloric and posture effects during LBNP were compared using two-way ANOVA with repeated measures. There was a strong trend toward reduced basal MSNA following caloric restriction alone (normcaloric vs. hypocaloric: 22±3 vs. 14±4 burst/min, p = 0.06). Compared to the normocaloric ambulatory, both bedrest and caloric restriction were associated with lower systolic blood pressure during LBNP (p<0.01); however, HR responses were directionally opposite (i.e., increase with bedrest, decrease with caloric restriction). Survival analysis revealed a significant reduction in orthostatic tolerance following caloric restriction (normocaloric finishers: 12/16; hypocaloric finishers: 6/16; χ2, p = 0.03). Caloric restriction modifies autonomic responses to LBNP, which may decrease orthostatic tolerance after spaceflight.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome.

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Characterizing sympathetic neurovascular transduction in humans.

Despite its critical role for cardiovascular homeostasis in humans, only a few studies have directly probed the transduction of sympathetic nerve activity to regional vascular responses--sympathetic neurovascular transduction. Those that have variably relied on either vascular resistance or vascular conductance to quantify the responses. However, it remains unclear which approach would better reflect the physiology. We assessed the utility of both of these as well as an alternative approach in 21 healthy men. We recorded arterial pressure (Finapres), peroneal sympathetic nerve activity (microneurography), and popliteal blood flow (Doppler) during isometric handgrip exercise to fatigue. We quantified and compared transduction via the relation of sympathetic activity to resistance and to conductance and via an adaptation of Poiseuille's relation including pressure, sympathetic activity, and flow. The average relationship between sympathetic activity and resistance (or conductance) was good when assessed over 30-second averages (mean R(2) = 0.49±0.07) but lesser when incorporating beat-by-beat time lags (R(2) = 0.37±0.06). However, in a third of the subjects, these relations provided relatively weak estimates (R(2)<0.33). In contrast, the Poiseuille relation reflected vascular responses more accurately (R(2) = 0.77±0.03, >0.50 in 20 of 21 individuals), and provided reproducible estimates of transduction. The gain derived from the relation of resistance (but not conductance) was inversely related to transduction (R(2) = 0.37, p<0.05), but with a proportional bias. Thus, vascular resistance and conductance may not always be reliable surrogates for regional sympathetic neurovascular transduction, and assessment from a Poiseuille relation between pressure, sympathetic nerve activity, and flow may provide a better foundation to further explore differences in transduction in humans.

Neural circulatory control during exercise: early insights.

During exercise, the cardiovascular response is rapidly and appropriately matched to the intensity of the physical activity. The autonomic nervous system plays an important role in achieving this closely matched circulatory response by an increase in the sympathetic nerve activity to the heart, blood vessels and adrenal medulla and a decrease in the parasympathetic nerve activity to the heart. Early insights into the mechanisms that controlled these cardiovascular changes during exercise were reported in the 19th century. At that time, two mechanisms were hypothesized to be responsible for these changes. In one mechanism, a signal arising in a central area of the brain causes a parallel activation of skeletal muscle contraction and of autonomic nervous system changes (now termed 'central command'). In the other mechanism, a signal arising in the contracting skeletal muscle causes a reflex activation of the autonomic nervous system changes (now termed 'exercise pressor reflex'). Some important investigators involved in early studies include Johan Johansson, August Krogh, Johannes Lindhard and Horace Smirk. Also, Florence Buchanan and Louis Fridericia should be recognized for their contributions. In more recent years, the important involvement of a third mechanism, the arterial baroreflex, has been elucidated. Since those early insights, experiments in both animals and humans have added important findings that strongly support these early hypotheses.

Failure to increase postprandial blood flow in subcutaneous adipose tissue is associated with tissue resistance to adrenergic stimulation.

AIMS: Adequate adipose tissue blood flow (ATBF) is essential for its metabolic and endocrine functions. From a metabolic point of view, sufficient increases in ATBF after meals permits full storage of excess energy into fat, thus protecting other tissues against the toxic effects of fatty acids and glucose spillover. It was previously shown that postprandial increases in ATBF are blunted in obese and insulin-resistant subjects, and that much of the postprandial ATBF response is the result of ß-adrenergic activation. Examination of previously recorded data on postprandial ATBF responses revealed an underlying heterogeneity, with postprandial ATBF being largely unresponsive to food stimuli in a substantial proportion of normal weight healthy people (low responders). Our study tests the hypothesis that this unresponsive pattern is due to resistance to ß-adrenergic stimulation in adipose tissue. METHODS: Five responders and five low responders were selected from a previously studied cohort and matched for BMI (20.5±0.7 vs 22±1 kg/m(2), respectively), gender (male/female: 2/3) and age (30±3 vs 37±6 years). Subcutaneous adipose tissue microinfusions of stepwise increasing doses of isoproterenol were performed with concomitant monitoring of blood flow, using the (133)Xenon washout technique. RESULTS: Although BMI was similar between responders and low responders, there were significant differences in fat mass (9.9±1.6 vs 14.4±1.6 kg; P<0.05) and four-point skinfold thickness (33±4 vs 52±16 mm; P<0.05). Lack of ATBF response to oral glucose was confirmed in the low responder group. In responders, ATBF was higher at baseline (5.4±1 vs 3.4±1 mL/min/100 g of tissue) and responded more distinctly to increasing isoproterenol doses (10(-8) M: 7.6±1.4 vs 4.9±1; 10(-6) M: 12.5±1.7 vs 7.5±1.6; and 10(-4) M: 20 ±1.7 vs 9±0.9 mL/min/100 g of tissue). CONCLUSION: These data suggest that the lack of glucose-stimulated ATBF is associated with resistance to sympathetic activation in adipose tissue.

Microanatomy of the neural scaffold of the pterygopalatine fossa in humans: trigeminovascular projections and trigeminal-autonomic plexuses.

The pterygopalatine fossa (PPF) is an anatomically-hidden deep extracranial space. The neural scaffold of the PPF remains anatomically understudied in humans. Moreover, there are no anatomical data in humans pointing out the extracranial trigeminovascular distributions, in contrast to the trigeminal supratentorial ones. By anatomical microdissections, the neural scaffold of the PPF and the presence of trigeminovascular projections were evaluated. The anterior and superior approaches of the pterygopalatine fossae in nine dissected blocks of human middle skull base and the frontal cuts of two different specimens, led to several results: (1) the neurovascular contents of the PPF, embedded in the pterygopalatine adipose body, have a layered disposition; (2) the posterior neural layer is represented by a pterygopalatine cross, centred by the pterygopalatine ganglion (PPG) that sends off ascending, descending, and medial branches and has a lateral connection with the maxillary nerve - 4 quadrants could have been defined as referring to this cross; (3) at the level of the upper lateral quadrant there are two superposed layers (i) a superficial plexus contributed by the maxillary nerve, the maxillary artery plexus and the PPG and its orbital branches (OBs) and (ii) a deep layer, consisting of the OBs proper of the PPG; (4) within the PPF and on the posterior wall of the maxillary sinus distinctive trigeminovascular projections were evidenced. The anastomoses involving autonomic and trigeminal fibres, located in the PPF passage to the orbital apex, support the complicate and polymorphous neural input to the orbit, while the evidence of a pterygopalatine trigeminovascular scaffold offers a substrate for a better understanding of various facial algias.

The effects of gender and test protocol on the results of head-up tilt test in patients with vasovagal syncope.

BACKGROUND: Head-up tilt testing (HUTT) is a well-established method for the diagnosis of reflex syncope. Some controversies exist whether gender and HUTT protocol influence HUTT results. AIM: To analyse the results of HUTT in patients with syncope in relation to their gender and used protocol of HUTT. METHODS: We retrospectively analysed data of 537 consecutive patients (313 women and 224 men), aged 13-79 years with history of neurally-mediated syncope referred to HUTT. The cardiogenic and neurological aetiology of syncope was excluded in all patients based on previous examination. In 375 patients standard HUTT (STD HUTT), according to the Westminster protocol, was used. In 257 patients in whom STD HUTT was negative, HUTT was continued with pharmacological provocation using isoproterenol intravenous infusion--114 patients (ISO HUTT) or sublingual nitroglycerin--143 patients (NTG HUTT). In the remaining 162 patients HUTT was performed according to the Italian protocol (ITL HUTT). The HUTT results were classified according to the VASIS scale. RESULTS: Female gender dominated, however, syncope was induced in a similar proportion of women and men (77.3 vs. 70.5%, NS). There were also no significant differences in the type of vasovagal response (VVR) to HUTT between women and men. Mixed type of VVR was the most frequent after isoproterenol provocation (ISO HUTT), whereas cardioinhibitory type of VVR was the most frequent after nitroglycerin provocation (NTG HUTT). CONCLUSIONS: There is no significant relationship between gender and the result of HUTT. The type of VVR is related to HUTT protocol--cardioinhibitory response is more frequent following nitroglycerin administration in comparison to standard protocol and HUTT with isoproterenol provocation.

Comparative study of the neuropeptide-Y sympathetic nerves in endometriotic involved and noninvolved sacrouterine ligaments in women with pelvic endometriosis.

STUDY OBJECTIVE: To show the relationship between the neuropeptide-Y pelvic sympathetic nerves and neoangiogenesis in the development of endometriosis DESIGN: Prospective study. SETTING: Academic community teaching hospital. PATIENTS: Fifteen consecutive women with unilateral endometriotic infiltration of the sacrouterine ligaments. INTERVENTIONS: A laparoscopic excision/biopsy of involved and noninvolved parts of the sacrouterine ligaments were taken. The sections were incubated with the neuronal marker rabbit polyclonal anti-protein gene product 9.5 and rabbit polyclonal anti-neuropeptide-Y. We made a comparative study on the distribution of nerve fibers and their relationship to the vessels on intact and endometriotic involved tissue. MEASUREMENTS AND MAIN RESULTS: The results show that a large amount of nerves are present around the blood vessels in the endometriosis samples, and a large number of these nerves are neuropeptide-Y sympathetic nerves. Adrenergic fibers are also present in the intact control subjects, however, in significantly smaller amounts. CONCLUSION: This finding shows a strong relationship between the neuropeptide-Y sympathetic pelvic nerves and the neoangiogenesis required for the development of endometriosis.

Effects of manual acupuncture with sparrow pecking on muscle blood flow of normal and denervated hindlimb in rats.

INTRODUCTION: In clinical practice, it has been thought that acupuncture might serve to wash out pain-generating metabolic end-products by improving blood circulation in muscles. We investigated the effects of manual acupuncture (MA) on muscle blood flow (MBF) of normal and denervated hindlimbs in rats. METHOD: Sprague-Dawley rats (n=100) anaesthetised with urethane (1.2g/kg ip) were used. Manual acupuncture with sparrow pecking (SP) at different doses (1, 10 or 30 pecks) was given to the right ventral hindlimb muscles (tibial anterior and extensor digitorum longus muscles) or the right dorsal hindlimb muscles (gastrocnemius, plantaris and soleus muscles). MBF with or without MA was measured using the radiolabelled microsphere technique. The blood pressure was recorded through the right common carotid artery until MBF measurement started. Denervation of hindlimb was conducted by cutting the sciatic and femoral nerves. RESULTS: In normal rats, significantly increased MBF after MA were observed only in muscles which were penetrated by an acupuncture needle. The size of the increase depended on the number of times of pecking and seemed to be sustained at least until 60 minutes after MA. However, the increase was observed after both acute and chronic denervation. On the other hand, the mean arterial blood pressure (MAP) did not change significantly before, during or after MA. CONCLUSION: These results suggest that MA could increase muscle blood flow locally in a dose-dependent manner and that this increase may be caused by local vasodilators, as well as the axon reflex. A further study is needed to elucidate the mechanism.

[Ergoreflex: the essence and mechanisms].

Physical loading raises the sympathetic nervous activity which results in increased minute volume, constriction of peripheral vessels, and elevated blood pressure. These reactions are an outcome of two mechanisms: 1) the central command from cerebral structures that trigger voluntary movements to activate the vasomotor center and 2) the reflexes initiated by mechanic and metabolic changes in a working muscle. The second mechanism of the sympathetic system activation was termed ergoreflex. Ergoreflex controls hemodynamics primarily through activation of mechanosensitive afferents to first of all inhibit the tonic vagal effects on the heart manifested by a leap of heart rate during loading. Activation of chemosensitive afferents comes with some delay in pace with metabolites accumulation in muscles and leads to growth of the efferent sympathetic activity and rise of blood pressure. The metabolic reflex effect is particularly high in the event of muscle fatigue. This review deals with the mechanisms underlying the ergoreflex and their adaptation to hypodynamia, physical loading, and also some pathologies.

Central command regulation of circulatory function mediated by descending pontine cholinergic inputs to sympathoexcitatory rostral ventrolateral medulla neurons.

Central command is a feedforward neural mechanism that evokes parallel modifications of motor and cardiovascular function during arousal and exercise. The neural circuitry involved has not been elucidated. We have identified a cholinergic neural circuit that, when activated, mimics effects on tonic and reflex control of circulation similar to those evoked at the onset of and during exercise. Central muscarinic cholinergic receptor (mAChR) activation increased splanchnic sympathetic nerve activity (SNA) as well as the range and gain of the sympathetic baroreflex via activation of mAChR in the rostral ventrolateral medulla (RVLM) in anesthetized artificially ventilated Sprague-Dawley rats. RVLM mAChR activation also attenuated and inhibited the peripheral chemoreflex and somatosympathetic reflex, respectively. Cholinergic terminals made close appositions with a subpopulation of sympathoexcitatory RVLM neurons containing either preproenkephalin mRNA or tyrosine hydroxylase immunoreactivity. M2 and M3 receptor mRNA was present postsynaptically in only non-tyrosine hydroxylase neurons. Cholinergic inputs to the RVLM arise only from the pedunculopontine tegmental nucleus. Chemical activation of this region produced increases in muscle activity, SNA, and blood pressure and enhanced the SNA baroreflex; the latter effect was attenuated by mAChR blockade. These findings indicate a novel role for cholinergic input from the pedunculopontine tegmental nucleus to the RVLM in central cardiovascular command. This pathway is likely to be important during exercise where a centrally evoked facilitation of baroreflex control of the circulation is required to maintain blood flow to active muscle.

Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment.

Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[18F]fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (-52+/-6 [SEM] versus -49+/-5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84+/-0.23 versus 1.33+/-0.35 ms/mm Hg during Valsalva; 0.43+/-0.09 versus 0.27+/-0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97+/-29 versus 71+/-23 pg/mL during orthostasis; -82+/-10 versus -73+/-8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193+/-19 pg/mL) than without (348+/-46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment.

How does cardiac resynchronization therapy improve exercise capacity in chronic heart failure?

BACKGROUND: Studies have shown that neither ejection fraction nor hemodynamic abnormalities during exercise in chronic heart failure (HF) correlate with symptoms of fatigue and exhaustion. The concept that exercise limitation in patients with chronic HF is due to abnormal hemodynamics during exercise has been revised to acknowledge that the skeletal myopathy of chronic HF contributes significantly to exercise dysfunction in heart failure. Why then does cardiac resynchronization therapy (CRT), a therapy that improves abnormalities of cardiac function, such as cardiac output and ejection fraction, produce a consistent, measurable, irrefutable increase in exercise capacity? METHODS AND RESULTS: In this review I will (1) review the mechanisms of exercise dysfunction in chronic HF, with special attention to the concept of "coordinated adaptation"; (2) analyze the effects of CRT on autonomic dysfunction in HF; and (3) propose a unifying hypothesis to understand how a therapy that improves cardiac function can improve exercise dysfunction attributable to a skeletal myopathy. Specifically, I will review evidence that CRT improves exercise capacity by attenuating the chronic sympathetic activation of HF. CONCLUSION: The decrease in sympathetic activation, and perhaps inflammation, during CRT likely reverses many features of the skeletal myopathy, leading to improved exercise capacity.

Comparison of continuous wave Doppler ultrasound of the radial artery and laser Doppler flowmetry of the fingertips with sympathetic stimulation.

Laser Doppler is widely used to evaluate sympathetic vasoconstrictor function. Continuous wave (cw)-Doppler of the radial artery may be an alternative but less expensive approach to quantify sympathetically induced resistance changes in the peripheral vascular system. In order to compare the power of both methods, this study was performed with simultaneous assessment of cw Doppler and laser Doppler flowmetry in volunteers. Twenty-five healthy subjects (median age years, range 20-27) rested in a relaxed supine position and were asked to perform a deep inspiratory gasp and a commanded cough (DIG + C). Radial artery blood flow was assessed with a standard cw Doppler device, arteriolar blood flow was assessed simultaneously employing a single point laser Doppler perfusion monitor at the fingertips. We quantified the latency between stimulus and onset of vasoconstriction, the latency to the maximum vasoconstriction and the duration of response. The decrease in flow velocities (cw Doppler) after stimulus was compared with the decrease in capillary flow (laser Doppler). While the flow profile as measured with laser Doppler remained monophasic after stimulation, cw Doppler showed biphasic flow (or absent diastolic flow) in all subjects after DIG + C. The latencies between stimulus and onset of reaction were significantly shorter when measured with laser Doppler (1.8 s vs. 2 s, p = 0.049), the latencies till the maximum extent of the reaction was reached did not differ significantly (3.2 vs. 3.3 s). The duration of the response was significantly shorter when measured by laser Doppler (12.0 vs. 14.5 s (p < 0.0001). While skin blood flow in the laser Doppler measurement decreased after stimulation from 654 flux units (FU) to 319 FU (-59%), mean flow velocities in the radial artery declined from 1.07 kHz to 0.14 kHz (-87%). This relative change was significantly different (p < 0.0001). The correlation between the decline of flux units as measured by laser Doppler and cw Doppler changes was r = 0.616 (p = 0.004). Both methods are feasible to monitor flow changes due to sympathetic stimulation. Latencies and relative quantitative changes were closely correlated.Thus, cw Doppler is a valid alternative approach to laser Doppler flowmetry in healthy volunteers.

[Adrenomedullin--the link between the sympathetic nervous system activation and peripheral vasodilatation in some patients with vasovagal syncope]. / Adrenomedullina-ogniwo laczace aktywacje ukladu wspólczulnego z obwodowa wazodylatacja u wybranych chorych z omdleniami wazowagalnymi.

UNLABELLED: Adrenomedullin (ADM) is a potent vasodilator playing role in regulation of central hemodynamic. The concentration of plasma ADM in healthy people increases under the influence of orthostatic stress. In patients with vasovagal syncope (VS) the changes in ADM concentration could be responsible either for syncope provocation or prevention. The aim of the study was to assess the influence of phase of the head-up tilt test (HUTT) in which the syncope occurred on the plasma concentration of ADM. MATERIAL AND METHODS: The study was performed in 25 patients (pts) (18 women and 7 men), mean age 45.0+/-16.1 years with cardiodepressive reactions during HUTT according to the Italian protocol with nitroglycerine (NTG) provocation if necessary: Syncope was caused in 23 pts due to vasovagal reaction: in 17 pts syncope occurred after NTG provocation (group 1), and in 6 pts occurred in the passive phase of tilt (group 2a), in 2 pts due to dysautonomic reactions (group 2b). The head-up tilt test was performed according to ESC guidelines. The blood for ADM concentration was drawn after 30 min supine rest (ADM 1) and immediately after syncope (ADM 2). ADM level was measured using radioimmunological method. The results. In group 1 plasma level of ADM significantly decreased after the HUTT (3.2+/-3.4 vs 1.7+/-1,4 pg/0.1 ml; p<0.05) and in group 2a increased significantly (1.3+/-0.8 vs 2.7+/-1.3 pg/0.1 ml; p<0.05) comparing to baseline values. The ADM concentration did not differ between the groups in baseline conditions and was significantly higher after the syncope in group 2a (p<0.05). Conclusions. The excessive increase of ADM concentration during the passive phase of HUTT could play the causative role in pathogenesis of VS occurring early during the HUTT. In patients with VS after NTG provocation the decrease of ADM concentration can be the result of hemodynamic changes in the presence of vasodilating drug and may be the mechanism that could prevent the syncope.

Sympathetic mechanisms in cerebral blood flow alterations induced by spinal cord stimulation.

OBJECT: Cervical spinal cord stimulation (SCS) has been found to augment cerebral blood flow (CBF) in a number of animal models, although the mechanisms underlying the cerebrovascular effects of SCS are poorly described. In this study, the authors examined the role of sympathetic tone in CBF alterations induced by SCS in rats. METHODS: Spinal cord stimulation was performed at three intervals while CBF was monitored with laser Doppler flowmetry (LDF). Either hexamethonium (5, 10, or 20 mg/kg), prazosin (0.25, 0.5, or 1 mg/kg), idazoxan (0.5, 1, or 2 mg/kg), propranolol (1, 2, or 4 mg/kg), or vehicle was administered intravenously before the second stimulation. Changes in LDF values due to SCS were recorded as the percentage of change from baseline values and were analyzed. In vehicle-treated animals, SCS increased LDF values by 60.5 +/- 1.8% over baseline, whereas both high-dose hexamethonium and prazosin completely abolished the SCS-induced increases in LDF values. On the other hand, LDF values increased by 50.9 +/- 4% and 61.4 +/- 4% after SCS in the presence of idazoxan or propranolol, respectively. Administration of sympathetic nervous system blockers resulted in a variable degree of systemic hypotension as well. Nevertheless, induced hypotension without sympathetic blockade had only a minimal effect on SCS-induced augmentation of LDF values (48 +/- 1.4% over baseline). CONCLUSIONS: Sympathetic tone plays a major role in SCS-induced increases in CBF. This effect seems to be mediated primarily by alpha1-adrenergic receptors. Systemic hypotension alone cannot explain the effects of sympathetic blockade on the SCS response. Clinical use of SCS in the treatment of cerebral ischemia should take alpha1-adrenergic receptor sympathetic tone into account.