Differential effects of hydrocortisone on sympathetic and hemodynamic responses to sympathoexcitatory manoeuvres in men

Aim of the present study was to investigate the influence of hydrocortisone on muscle sympathetic nerve activity (MSNA) and hemodynamic parameters during different sympathoexcitatory manoeuvres in humans. The study focuses on the interaction of the hypothalamo-pituitary-adrenal system and the sympathetic nervous system. Hydrocortisone 100 mg or placebo was administered intravenously to eight young healthy subjects in a double-blind crossover design. After 6 h, blood pressure, heart rate and MSNA from the peroneal nerve were recorded at rest, during an arithmetic stress task, an apnea and a cold pressor test. Hydrocortisone treatment increased serum cortisol levels to the upper physiological range and suppressed basal levels of adrenocorticotropin. During mental stress, MSNA, heart rate and blood pressure levels were elevated independently of hydrocortisone pre-treatment. However, hydrocortisone induced a sustained increase in basal heart rate throughout the whole experiment. A stronger increase in diastolic blood pressure was observed during apnea and cold pressor test in the hydrocortisone experiments. MSNA or plasma catecholamines at rest or during the manoeuvres were not affected by hydrocortisone. The observed hydrocortisone effects may be due to an increased responsiveness of adrenergic receptors towards catecholamines or a central modulation of the baroreflex involving parasympathetic mechanisms. Further studies are needed to confirm that the increase in MSNA during mental stress does not depend on a concomitant activation of the hypothalamo-pituitary-adrenal system.     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt

To test the hypothesis that systemic inhibition of nitric oxide (NO) synthase does not alter the regulation of sympathetic outflow during head-up tilt in humans, in eight healthy subjects NO synthase was blocked by intravenous infusion of NG-monomethyl-L-arginine (L-NMMA). Blood pressure, heart rate, cardiac output, total peripheral resistance (TPR), and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and during 60 degrees head-up tilt. In the supine position, infusion of L-NMMA increased blood pressure, via increased TPR, and inhibited MSNA. However, the increase in MSNA evoked by head-up tilt during L-NMMA infusion (change in burst rate: 24 +/- 4 bursts/min; change in total activity: 209 +/- 36 U/min) was similar to that during head-up tilt without L-NMMA (change in burst rate: 23 +/- 4 bursts/min; change in total activity: 251 +/- 52 U/min, n = 6, all P > 0.05). Moreover, changes in TPR and heart rate during head-up tilt were virtually identical between the two conditions. These results suggest that systemic inhibition of NO synthase with L-NMMA does not affect the regulation of sympathetic outflow and vascular resistance during head-up tilt in humans.     

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

Relationship between blood pressure,sleep K-complexes,and muscle sympathetic nerve activity in humans

Stage 2 sleep is characterized by the EEG appearance of "K-complexes" and blood pressure oscillations. K-complexes may be directly related to blood pressure changes or they may reflect central sympathetic activation. We analyzed the temporal relationship among K-complexes, heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) during sleep in eight healthy volunteers (3 men and 5 women, age 22-41 yr). Most K-complexes presented as single large complexes (56 +/- 20%), followed by single small complexes (15 +/- 14%) and as couplets or triplets (13 +/- 6%). Single large K-complexes were preceded by a baroreflex-mediated increase of MSNA in approximately one-half (55%) of the cases. Detailed analysis of HR, BP, and MSNA was possible in 63 (45%) large single K-complexes not disturbed by preceding baroreflex-related changes. Systolic and diastolic BP and MSNA increased significantly after single events (22.5 +/- 13, 5.2 +/- 2.1, and 6.5 +/- 3.0%). Mean sympathetic baroreflex latency was similar after the single large K-complexes compared with the mean value during stage 2 sleep (1,290 +/- 126 vs. 1,279 +/- 61 ms). The area under the burst was significantly increased after single large K-complexes (median 3.9 vs. 9.0 arbitrary units, P < 0.03). The results support the hypothesis that K-complexes express cortical activation leading to temporary facilitation of sympathetic outflow in a graded fashion. Their functional effects appear to be independent of baroreflex modulation of MSNA in approximately 50% of the cases.     

Vestibulosympathetic reflex during mental stress.

Increases in sympathetic neural activity occur independently with either vestibular or mental stimulation, but it is unknown whether sympathetic activation is additive or inhibitive when both stressors are combined. The purpose of the present study was to investigate the combined effects of vestibular and mental stimulation on sympathetic neural activation and arterial pressure in humans. Muscle sympathetic nerve activity (MSNA), arterial pressure, and heart rate were recorded in 10 healthy volunteers in the prone position during 1) head-down rotation (HDR), 2) mental stress (MS; using arithmetic), and 3) combined HDR and MS. HDR significantly (P < 0.05) increased MSNA (9 +/- 2 to 13 +/- 2 bursts/min). MS significantly increased MSNA (8 +/- 2 to 13 +/- 2 bursts/min) and mean arterial pressure (87 +/- 2 to 101 +/- 2 mmHg). Combined HDR and MS significantly increased MSNA (9 +/- 1 to 16 +/- 2 bursts/min) and mean arterial pressure (89 +/- 2 to 100 +/- 3 mmHg). Increases in MSNA (7 +/- 1 bursts/min) during the combination trial were not different from the algebraic sum of each trial performed alone (8 +/- 2 bursts/min). We conclude that the interaction for MSNA and arterial pressure is additive during combined vestibular and mental stimulation. Therefore, vestibular- and stress-mediated increases of MSNA appear to occur independently in humans.     

Aldosterone impairs baroreflex sensitivity in healthy adults

Animal studies suggest that acute and chronic aldosterone administration impairs baroreceptor/baroreflex responses. We tested the hypothesis that aldosterone impairs baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA, sympathetic BRS) in humans. Twenty-six young (25 +/- 1 yr old, mean +/- SE) adults were examined in this study. BRS was determined by using the modified Oxford technique (bolus infusion of nitroprusside, followed 60 s later by bolus infusion of phenylephrine) in triplicate before (Pre) and 30-min after (Post) beginning aldosterone (experimental, 12 pmol.kg(-1).min(-1); n = 10 subjects) or saline infusion (control; n = 10). BRS was quantified from the R-R interval-systolic blood pressure (BP) (cardiovagal BRS) and MSNA-diastolic BP (sympathetic BRS) relations. Aldosterone infusion increased serum aldosterone levels approximately fourfold (P < 0.05) and decreased (P < 0.05) cardiovagal (19.0 +/- 2.3 vs. 15.6 +/- 1.7 ms/mmHg Pre and Post, respectively) and sympathetic BRS [-4.4 +/- 0.4 vs. -3.0 +/- 0.4 arbitrary units (AU).beat(-1).mmHg(-1)]. In contrast, neither cardiovagal (19.3 +/- 3.3 vs. 20.2 +/- 3.3 ms/mmHg) nor sympathetic BRS (-3.8 +/- 0.5 vs. -3.6 +/- 0.5 AU.beat(-1).mmHg(-1)) were altered (Pre vs. Post) in the control group. BP, heart rate, and MSNA at rest were similar in experimental and control subjects before and after the intervention. Additionally, neural and cardiovascular responses to a cold pressor test and isometric handgrip to fatigue were unaffected by aldosterone infusion (n = 6 subjects). These data provide direct experimental support for the concept that aldosterone impairs baroreflex function (cardiovagal and sympathetic BRS) in humans. Therefore, aldosterone may be an important determinant/modulator of baroreflex function in humans.     

Ghrelin modulates baroreflex-regulation of sympathetic vasomotor tone in healthy humans

Ghrelin, a neuropeptide originally known for its growth hormone-releasing and orexigenic properties, exerts important pleiotropic effects on the cardiovascular system. Growing evidence suggests that these effects are mediated by the sympathetic nervous system. The present study aimed at elucidating the acute effect of ghrelin on sympathetic outflow to the muscle vascular bed (muscle sympathetic nerve activity, MSNA) and on baroreflex-mediated arterial blood pressure (BP) regulation in healthy humans. In a randomized double-blind cross-over design, 12 lean young men were treated with a single dose of either ghrelin 2 μg/kg iv or placebo (isotonic saline). MSNA, heart rate (HR), and BP were recorded continuously from 30 min before until 90 min after substance administration. Sensitivity of arterial baroreflex was repeatedly tested by injection of vasoactive substances based on the modified Oxford protocol. Early, i.e., during the initial 30 min after ghrelin injection, BP significantly decreased together with a transient increase of MSNA and HR. In the course of the experiment (>30 min), BP approached placebo level, while MSNA and HR were significantly lower compared with placebo. The sensitivity of vascular arterial baroreflex significantly increased at 30-60 min after intravenous ghrelin compared with placebo, while HR response to vasoactive drugs was unaltered. Our findings suggest two distinct phases of ghrelin action: In the immediate phase, BP is decreased presumably due to its vasodilating effects, which trigger baroreflex-mediated counter-regulation with increases of HR and MSNA. In the delayed phase, central nervous sympathetic activity is suppressed, accompanied by an increase of baroreflex sensitivity.     

PET(CO(2)) inversely affects MSNA response to orthostatic stress

Arterial hypocapnia has been associated with orthostatic intolerance. Therefore, we tested the hypothesis that hypocapnia may be detrimental to increases in muscle sympathetic nerve activity (MSNA) and total peripheral resistance (TPR) during head-up tilt (HUT). Ventilation was increased approximately 1.5 times above baseline for each of three conditions, whereas end-tidal PCO(2) (PET(CO(2))) was clamped at normocapnic (Normo), hypercapnic (Hyper; +5 mmHg relative to Normo), and hypocapnic (Hypo; -5 mmHg relative to Normo) conditions. MSNA (microneurography), heart rate, blood pressure (BP, Finapres), and cardiac output (Q, Doppler) were measured continuously during supine rest and 45 degrees HUT. The increase in heart rate when changing from supine to HUT (P < 0.001) was not different across PET(CO(2)) conditions. MSNA burst frequency increased similarly with HUT in all conditions (P < 0.05). However, total MSNA and the increase in total amplitude relative to baseline (%DeltaMSNA) increased more when changing to HUT during Hypo compared with Hyper (P < 0.05). Both BP and Q were higher during Hyper than both Normo and Hypo (main effect; P < 0.05). Therefore, the MSNA response to HUT varied inversely with levels of PET(CO(2)). The combined data suggest that augmented cardiac output with hypercapnia sustained blood pressure during HUT leading to a diminished sympathetic response.     

Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans

Volume expansion often ameliorates symptoms of orthostatic intolerance; however, the influence of this increased volume on integrated baroreflex control of vascular sympathetic activity is unknown. We tested whether acute increases in central venous pressure (CVP) diminished subsequent responsiveness of muscle sympathetic nerve activity (MSNA) to rapid changes in arterial pressure. We studied healthy humans under three separate conditions: control, acute 10 degrees head-down tilt (HDT), and saline infusion (SAL). In each condition, heart rate, arterial pressure, CVP, and peroneal MSNA were measured during 5 min of rest and then during rapid changes in arterial pressure induced by sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). Sensitivities of integrated baroreflex control of MSNA and heart rate were assessed as the slopes of the linear portions of the MSNA-diastolic blood pressure and R-R interval-systolic pressure relations, respectively. CVP increased approximately 2 mmHg in both SAL and HDT conditions. Resting heart rate and mean arterial pressure were not different among trials. Sensitivity of baroreflex control of MSNA was decreased in both SAL and HDT condition, respectively: -3.1 +/- 0.6 and -3.3 +/- 1.0 versus -5.0 +/- 0.6 units.beat(-1).mmHg(-1) (P < 0.05 for SAL and HDT vs. control). Sensitivity of baroreflex control of the heart was not different among conditions. Our results indicate that small increases in CVP decrease the sensitivity of integrated baroreflex control of sympathetic nerve activity in healthy humans.     

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats

We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD-induced decreases in BP and HR responses. Efferent chronotropic responses involve both increased parasympathetic and reduced sympathetic activity, whereas the decrease in BP is mediated by reduced α-adrenergic tone.     

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.     

Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night.

Melatonin increases sleepiness, decreases core temperature, and increases peripheral temperature in humans. Melatonin may produce these effects by activating peripheral receptors or altering autonomic activity. The latter hypothesis was investigated in 16 supine subjects. Three conditions were created by using bright light and exogenous melatonin: normal endogenous, suppressed, and pharmacological melatonin levels. Data during wakefulness from 1.5 h before to 2.5 h after each subject's estimated melatonin onset (wake time + 14 h) were analyzed. Respiratory sinus arrhythmia (cardiac parasympathetic activity) and preejection period (cardiac sympathetic activity) did not vary among conditions. Pharmacological melatonin levels significantly decreased systolic blood pressure [5.75 +/- 1.65 (SE) mmHg] but did not significantly change heart rate. Suppressed melatonin significantly increased rectal temperature (0.27 +/- 0.06 degrees C), decreased foot temperature (1.98 +/- 0.70 degrees C), and increased sleep onset latency (5.53 +/- 1.87 min). Thus melatonin does not significantly alter cardiac autonomic activity and instead may bind to peripheral receptors in the vasculature and heart. Furthermore, increases in cardiac parasympathetic activity before normal nighttime sleep cannot be attributed to the concomitant increase in endogenous melatonin.     

Autonomic Activity Assessed by Heart Rate Spectral Analysis Varies with Fat Distribution in Obese Women

Obesity in humans has been associated with altered autonomic nervous system activity. The objective of this study was to examine the relationship between autonomic function and body fat distribution in 16 obese, postmenopausal women using power spectrum analysis of heart rate variability. Using this technique, a low frequency peak (0.04-0.12 Hz) reflecting mixed sympathetic and parasympathetic activity, and a high frequency peak (0.22-0.28 Hz) reflecting parasympathetic activity, were identified from 5-minute consecutive heart rate data (both supine and standing). Autonomic activity in upper body (UBO) vs. lower body obesity (LBO)(by waist-to-hip ratio) and subcutaneous vs. visceral obesity (by CT scan) was evaluated. Power spectrum data were log transformed to normalize the data. The results showed that standing, low-frequency power (reflecting sympathetic activity) and supine, high-frequency power (reflecting parasympathetic activity) were significantly greater in UBO than in LBO, and in visceral compared to subcutaneous obesity. Women with combined UBO and visceral obesity had significantly higher cardiac sympathetic and parasympathetic activity than any other subgroup. We conclude that cardiac autonomic function as assessed by heart rate spectral analysis varies in women depending on their regional body fat distribution.     

Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 +/- 1 mosmol/kg in C to 290 +/- 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 +/- 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 +/- 0.97 (HT1) vs. -5.85 +/- 0.63 (C) arbitrary units (au).beat(-1).mmHg(-1); P < 0.01] but was not different in HT2 (-6.55 +/- 0.94 au.beat(-1).mmHg(-1)). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP.     

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n=9, 1 mg/day) or placebo (n=9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59+/-2 vs. 71+/-2 beats/min, P<0.01). In both groups, exercise produced significant decreases in systolic BP (145+/-3 vs. 154+/-3 mmHg, P=0.01), diastolic BP (71+/-3 vs. 75+/-2 mmHg, P=0.04), mean BP (89+/-2 vs. 93+/-2 mmHg, P=0.02), MSNA (29+/-2 vs. 35+/-1 bursts/min, P<0.01), and FVR (33+/-4 vs. 55+/-10 units, P=0.01), whereas it increased FBF (2.7+/-0.4 vs. 1.6+/-0.2 ml x min(-1) x 100 ml(-1), P=0.02) and did not change HR (64+/-2 vs. 65+/-2 beats/min, P=0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.     

Effect of aging on baroreflex function in humans

Arterial blood pressure (BP) is regulated via the interaction of various local, humoral, and neural factors. In humans, the major neural pathway for acute BP regulation involves the baroreflexes. In response to baroreceptor activation/deactivation, as occurs during transient changes in BP, key determinants of BP, such as cardiac period/heart rate (via the sympathetic and parasympathetic nervous system) and vascular resistance (via the sympathetic nervous system), are modified to maintain BP homeostasis. In this review, the effects of aging on both the parasympathetic and sympathetic arms of the baroreflex are discussed. Aging is associated with decreased cardiovagal baroreflex sensitivity (i.e., blunted reflex changes in R-R interval in response to a change in BP). Mechanisms underlying this decrease may involve factors such as increased levels of oxidative stress, vascular stiffening, and decreased cardiac cholinergic responsiveness with age. Consequences of cardiovagal baroreflex impairment may include increased levels of BP variability, an impaired ability to respond to acute challenges to the maintenance of BP, and increased risk of sudden cardiac death. In contrast, baroreflex control of sympathetic outflow is not impaired with age. Collectively, changes in baroreflex function with age are associated with an impaired ability of the organism to buffer changes in BP. This is evidenced by the reduced potentiation of the pressor response to bolus infusion of a pressor drug after compared to before systemic ganglionic blockade in older compared with young adults.     

Sympathetic overactivity in active ulcerative colitis: effects of clonidine

Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LF(RR); normalized units) and high-frequency (HF) parasympathetic (HF(RR); normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LF(SAP)), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LF(RR), LF/HF, and LF(SAP) were higher and HF(RR) was lower in patients than in controls. Tilt decreased HF(RR) and increased MSNA and LF(RR) less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LF(RR), and increased HF(RR), whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.