Free dopamine in dog plasma: lack of relationship with sympathoadrenal activity

To investigate the relationship between dopamine (DA) released into the bloodstream and sympathoadrenal activity, levels of free DA, norepinephrine (NE), and epinephrine (E) in plasma were recorded in four dogs subjected to three tests: treadmill exercise at two work levels [55 and 75% maximal O2 uptake; 15 min], normobaric hypoxia (12% O2; 1 h), combined exercise and hypoxia. Normoxic exercise induced slight nonsignificant decreases in the arterial partial pressure of O2 (PaO2), increases in NE [median values and ranges during submaximal work vs. rest: 1086 (457-1,637) vs. 360 (221-646) pg/ml; P less than 0.01] and E [277 (151-461) vs. 166 (95-257) pg/ml; P less than 0.05], but it failed to alter the DA level. Hypoxia elicited large decreases in PaO2 [hypoxia vs. normoxia: 42.8 (40.3-50.0) vs. 97.6 (83.2-117.6) Torr; P less than 0.01], increases in DA [230 (105-352) vs. 150 (85-229) pg/ml; P less than 0.01] and NE [383 (219-1,165) vs. 358 (210-784) pg/ml; P less than 0.05], but it failed to alter the E level. Combined exercise and hypoxia further increased NE levels but did not alter the DA response to hypoxia alone. The data indicate that free DA in plasma may vary independently of the sympathoadrenal activity.     

Fluid volume and osmoregulation in humans after a week of head-down bed rest

Body fluid homeostasis was investigated during chronic bed rest (BR) and compared with that of acute supine conditions. The hypothesis was tested that 6 degrees head-down BR leads to hypovolemia, which activates antinatriuretic mechanisms so that the renal responses to standardized saline loading are attenuated. Isotonic (20 ml/kg body wt) and hypertonic (2.5%, 7.2 ml/kg body wt) infusions were performed in eight subjects over 20 min following 7 and 10 days, respectively, of BR during constant sodium intake (200 meq/day). BR decreased body weight (83.0 +/- 4.8 to 81.8 +/- 4.4 kg) and increased plasma osmolality (285.9 +/- 0.6 to 288.5 +/- 0.9 mosmol/kgH(2)O, P < 0.05). Plasma ANG II doubled (4.2 +/- 1.2 to 8.8 +/- 1.8 pg/ml), whereas other endocrine variables decreased: plasma atrial natriuretic peptide (42 +/- 3 to 24 +/- 3 pg/ml), urinary urodilatin excretion rate (4.5 +/- 0.3 to 3.2 +/- 0.1 pg/min), and plasma vasopressin (1.7 +/- 0.3 to 0.8 +/- 0.2 pg/ml, P < 0.05). During BR, the natriuretic response to the isotonic saline infusion was augmented (39 +/- 8 vs. 18 +/- 6 meq sodium/350 min), whereas the response to hypertonic saline was unaltered (32 +/- 8 vs. 29 +/- 5 meq/350 min, P < 0.05). In conclusion, BR elicits antinatriuretic endocrine signals, but it does not attenuate the renal natriuretic response to saline stimuli in men; on the contrary, the response to isotonic saline is augmented.     

Specific binding of atrial natriuretic factor to renal glomeruli during day or night antiorthostatic suspension in the rat

We observed a significant increase in plasma atrial natriuretic factor (ANF) in antiorthostatic hypokinetic suspension (AOH) rats after 2 h of suspension when the experiment was made during day. Plasma ANF was investigated in relation to renal glomerular ANF receptors during AOH at night. The aim of this study was 1) to compare the day and night ANF responses to AOH 2) to determine whether the renal glomerular ANF receptors are involved. The rats were divided into 2 groups: i) 24 population cage (PC), and ii) 24 were attached by the tail (Morey's model) and remained in the horizontal position (attached horizontal-AH). Six AH were suspended (30 degrees) for 2 hours (AOH) and sacrificed with the controls: PC and AH (12.00h). The same experiment was made during the night (24.00h). A significant increase in plasma ANF was found in both AOH and AH after 2 h of suspension during day and night (19 +/- 2.3 pg/ml vs 9 +/- 0.95 and 18 +/- 3 pg/ml vs 10.2 +/- 1.8 respectively). PC rats had a significantly higher ANF level (38 +/- 5 pg/ml) than AH or AOH. The glomerular ANF receptor population was slightly lower in AOH than in AH (429 +/- 12 fmol/mg protein vs 507 +/- 5) during day. During night, a significantly lower number of ANF receptors was observed in AOH animals as compared to AH (168 +/- 2 fmol/mg protein vs 455 +/- 3). A decrease in glomerular receptors was also noted in PC during night. Day-time head-down tilt, bed rest or head-out water induced a natriuretic and diuretic response, whereas the normal recumbency at night does not lead to such effects. We conclude that the natriuretic and diuretic response not observed during night was associated with elevated plasma ANF levels and decreased ANF receptor density.     

Sympathoadrenomedullary hyper-responsiveness to yohimbine in juvenile spontaneously hypertensive rats

We examined responses of arterial plasma levels of the sympathetic neurotransmitter, norepinephrine (NE), of the adrenomedullary hormone, epinephrine (E), and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG), after intravenous administration of the alpha-2 adrenoceptor antagonist, yohimbine, in conscious, freely-moving juvenile (4-week old) or mature (12-week old) rats with spontaneous hypertension (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Mature SHRs and WKY rats had similar levels of plasma catechols at rest, whereas juvenile SHRs had significantly higher levels of NE (400 +/- 109 (SD) vs 233 +/- 62 pg/ml), E (371 +/- 168 vs 148 +/- 67 pg/ml), and DHPG (800 +/- 147 vs 589 +/- 54 pg/ml). After yohimbine, average responses of NE in the juvenile SHRs were more than 5 times, of E more than 7 times, and of DHPG more than 11 times those of the juvenile WKY rats. The responses of plasma catechols to yohimbine were not excessive in mature 12-week old SHRs. The results demonstrate increased sympathoadrenomedullary activity at rest and markedly enhanced sympathoadrenomedullary responsiveness to yohimbine in juvenile but not mature SHRs and are consistent with the hypothesis that early in the development of hypertension in this laboratory animal model there is an abnormal dependence on central neural alpha-2 adrenoceptors as part of an incompletely successful compensatory mechanism for limiting sympathetic outflow.     

Prolonged exercise following diuretic-induced hypohydration effects on fluid and electrolyte hormones.

To investigate the hypothesis that a reduction in plasma volume (PV) induced by diuretic administration would result in an increase in the fluid and electrolyte hormonal response to exercise, ten untrained males (VO(2) peak = 3.96 +/- 0.14 l/min) performed 60 min of cycle ergometry at 61 % VO(2) peak twice. The test was carried out once under control conditions (CON) (placebo) and once after 4 days of diuretic administration (DIU) (Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). Calculated resting PV decreased by 14.6 +/- 3.3 % (p < 0.05) with DIU. No difference in plasma osmolality was observed between conditions. For the hormones measured, differences (p < 0.05) between conditions at rest were noted for plasma renin activity (PRA) (0.62 +/- 0.09 vs. 5.61 +/- 0.94 ng/ml/h), angiotensin I (ANG 1) (0.26 +/- 0.03 vs. 0.56 +/- 0.08 ng/ml), aldosterone (ALD) (143 +/- 14 vs. 1603 +/- 302 pg/ml), arginine vasopressin (AVP) (4.13 +/- 1.1 vs. 9.58 +/- 1.6 pg/ml) and atrial natriuretic peptide (alpha-ANP) (11.5 +/- 2.8 vs. 6.33 +/- 1.0 pg/ml). The exercise resulted in increases (p < 0.05) in PRA, ANG I, ALD, AVP, alpha-ANP. DIU led to higher levels of PRA, ANG I, and ALD (p < 0.05) and lower levels of alpha-ANP (p < 0.05) compared to CON. Arginine vasopressin was not affected by the loss of PV. For the catecholamines--norepinephrine (NE) and epinephrine (EPI)--only NE was higher during exercise with DIU compared to CON (p < 0.05). For PRA and ALD, the higher levels observed during exercise with DIU could be explained both by higher resting levels and a greater increase during exercise itself. For ANG I and NE, the effect of DIU only manifested itself during exercise. In contrast, the lower alpha-ANP observed during exercise with DIU was due to the lower resting levels. These results support the hypotheses that hypohydration leads to alterations in the secretion of all of the fluid and electrolyte hormones with the exception of AVP. The specific mechanisms of these alterations remain unclear, but appear to be related directly to the decrease in PV.     

Sympathetic nervous activity decreases during head-down bed rest but not during microgravity.

We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy subjects were studied before and during HDBR of 2-wk duration, as well as during an ambulatory study period of a similar length. Platelet norepinephrine concentrations (half-life = 2 days) were studied in five cosmonauts, 2 wk before launch, within 12 h after landing after 11-12 days of flight, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P < 0.001), whereas there were no significant changes when subjects were ambulatory. Platelet epinephrine did not change during HDBR. During microgravity, platelet norepinephrine and epinephrine increased in four of the five cosmonauts. Platelet norepinephrine concentrations expressed in percentage of preflight and pre-HDBR values, respectively, were significantly different during microgravity compared with HDBR [153 +/- 28% (mean +/- SE) vs. 60 +/- 6%, P < 0.004]. Corresponding values for platelet epinephrine were also significant (293 +/- 85 vs. 90 +/- 12%, P < 0.01). The mechanism of the platelet norepinephrine and epinephrine response during spaceflight flight is most likely related to the concomitant decrease in plasma volume. HDBR cannot be applied to simulate changes in sympathoadrenal activity during microgravity.     

Evidence for increased hepatic sympathetic nerve activity resulting in hyperglycemia in response to hemorrhage-induced reflex stimulation in anesthetized dogs

To investigate the role of the sympathoadrenal system in glucose mobilization by the liver during hemorrhage, catecholamine (CA) output from both adrenal glands was determined in anesthetized dogs. Venous blood draining from both adrenal glands was combined in a Y-tube that was connected to an electromagnetic flow probe to measure total adrenal venous blood flow. Plasma concentrations of norepinephrine (NE), epinephrine (E), dopamine (DA), and glucose (GL) were determined in various vascular regions. Adrenal CA output (nanograms per minute) under basal conditions was 50.2 +/- 13.6, 181.4 +/- 41.9, and 13.7 +/- 4.8 for NE, E, and DA, respectively. These values were found to increase significantly (P less than 0.05) in response to 5 min of hemorrhage, reaching a maximum output (nanograms per minute) of 663.6 +/- 160.6 (NE), 2503.4 +/- 607.8 (E), and 141.7 +/- 43.7 (DA). Aortic CAs (nanograms per millilitre) increased significantly with a predominant increase in E (0.33 +/- 0.08 to 3.75 +/- 1.03, P less than 0.05). In contrast, increases in portal and hepatic venous CAs (nanograms per millilitre) were characterized by a predominant increase in NE (0.30 +/- 0.06 to 0.64 +/- 0.11 and 0.17 +/- 0.02 to 0.31 +/- 0.07, respectively, P less than 0.05). Hepatic venous and aortic GL concentrations also increased significantly during hemorrhage. Among the various correlations between plasma CA and GL concentrations, the strongest correlation was found between hepatic venous NE and hepatic venous GL (r = 0.804, P less than 0.001). Correlation coefficients obtained with aortic NE and E were weaker but significant (r = 0.603 and r = 0.608, respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Catecholamine response is attenuated during moderate-intensity exercise in response to the "lactate clamp"

Catecholamine release is known to be regulated by feedforward and feedback mechanisms. Norepinephrine (NE) and epinephrine (Epi) concentrations rise in response to stresses, such as exercise, that challenge blood glucose homeostasis. The purpose of this study was to assess the hypothesis that the lactate anion is involved in feedback control of catecholamine concentration. Six healthy active men (26 +/- 2 yr, 82 +/- 2 kg, 50.7 +/- 2.1 ml.kg(-1).min(-1)) were studied on five occasions after an overnight fast. Plasma concentrations of NE and Epi were determined during 90 min of rest and 90 min of exercise at 55% of peak O2 consumption (VO2 peak) two times with exogenous lactate infusion (lactate clamp, LC) and two times without LC (CON). The blood lactate profile ( approximately 4 mM) of a preliminary trial at 65% VO2 peak (65%) was matched during the subsequent LC trials. In resting men, plasma NE concentration was not different between trials, but during exercise all conditions were different with 65% > CON > LC (65%: 2,115 +/- 166 pg/ml, CON: 1,573 +/- 153 pg/ml, LC: 930 +/- 174 pg/ml, P < 0.05). Plasma Epi concentrations at rest were different between conditions, with LC less than 65% and CON (65%: 68 +/- 9 pg/ml, CON: 59 +/- 7 pg/ml, LC: 38 +/- 10 pg/ml, P < 0.05). During exercise, Epi concentration showed the same trend (65%: 262 +/- 37 pg/ml, CON: 190 +/- 34 pg/ml, LC: 113.2 +/- 23 pg/ml, P < 0.05). In conclusion, lactate attenuates the catecholamine response during moderate-intensity exercise, likely by feedback inhibition.     

Dissociation of hypothalamic noradrenergic activity and sympathoadrenal responses to recurrent hypoglycemia

This study evaluated whether attenuation of sympathoadrenal responses to recurrent hypoglycemia is mediated by diminished noradrenergic activity in the hypothalamus. Male Sprague-Dawley rats received either once daily insulin (1.0 units/kg) injections or an equal administration of saline for 3 days. Both groups received an administration of insulin on the fourth day, during which blood glucose and plasma catecholamines were determined, and extracellular norepinephrine (NE) in the ventromedial hypothalamus (VMH) or paraventricular hypothalamic nucleus (PVN) was monitored with microdialysis. The peak response of plasma epinephrine to insulin-induced hypoglycemia (nadir approximately 3.2 mmol/l) was significantly reduced during the fourth hypoglycemic episode (774 +/- 134 pg/ml) compared with the first episode (2,561 +/- 410 pg/ml, P < 0.001). Baseline levels of extracellular NE were elevated approximately 25% (P = 0.07) in the VMH and approximately 46% (P = 0.03) in the PVN after multiple hypoglycemic episodes. There was no difference in noradrenergic activity during the first or fourth hypoglycemic episode in either brain area. The reduced sympathoadrenal output after recurrent hypoglycemia is likely postsynaptic from hypothalamic NE release or is mediated via a collateral pathway.     

Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest.

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.     

Effects of vasomotor- and mediator-induced hypotension on bronchomotor tone in swine

We studied the sympathetic neural response on airways to hypotensive stimuli in 19 swine in vivo. The effects of pharmacologically induced hypotension with nitroprusside (NTP) and hypotension elicited by intravenous compound 48/80 (48/80), a mast cell degranulating agent, were compared after equivalent reductions in mean arterial blood pressure (MAP). Reduction of the MAP to 60% of base line with NTP in six swine caused an increase in plasma epinephrine (E) from 60 +/- 28 to 705 +/- 276 pg/ml (P = 0.032) and plasma norepinephrine (NE) from 270 +/- 46 to 796 +/- 131 pg/ml (P = 0.032). Comparable reduction in MAP elicited with 48/80 in six other swine caused a substantially greater increase in both plasma E (9,581 +/- 4,147 pg/ml; P = 0.012 vs. NTP group) and plasma NE (2,239 +/- 637 pg/ml; P = 0.041 vs. NTP group). Catecholamine secretion attenuated mediator-induced changes in lung resistance (RL). In animals receiving 48/80, RL increased from 2.97 +/- 0.31 to 7.44 +/- 0.56 cmH2O.l-1.s. In animals having ganglionic blockade with 7.5 mg/kg iv hexamethonium and beta-adrenergic blockade with propranolol (4.0 mg/kg iv followed by 40 micrograms/kg-1.min-1), comparable doses of 48/80 caused an increase in RL to 18.6 +/- 4.55 cmH2O.l-1.s (P less than 0.04 vs. swine receiving neither hexamethonium nor propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration

Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an apparent abnormality of baroreflex regulation of cardiac period. In a previous study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute induced hypovolemia led to similar impairments in spontaneous baroreflex control of cardiac period, suggesting that a reduction in plasma volume may be responsible for this abnormality after bed rest. Therefore we hypothesized that this reduced "baroreflex function" could be restored by intravenous volume infusion equivalent to the reduction in plasma volume after bed rest. Six healthy subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial blood pressure and ECG were recorded during 6 min of spontaneous respiration and fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic blood pressure and R-R interval was performed. Plasma volume was measured with Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz catheter). After bed rest, studies were repeated before and after plasma volume restoration, with which both plasma volume and left ventricular end-diastolic pressure were restored to pre-bed rest levels by intravenous dextran40 infusion (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an index of vagally mediated arterial-cardiac baroreflex function, decreased significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest. However, reduced transfer function gain was normalized to the pre-bed rest level (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result confirms that reductions in plasma volume, rather than a unique autonomic nervous system adaptation to bed rest, are largely responsible for the observed changes in spontaneous arterial-cardiac baroreflex function after bed rest.     

Hemodynamic, gas exchange, and hormonal consequences of LBPP during PEEP ventilation

Hemodynamic, gas exchange, and hormonal response induced by application of a 25- to 40-mmHg lower body positive pressure (LBPP), during positive end-expiratory pressure (PEEP; 14 +/- 2.5 cmH2O) were studied in nine patients with acute respiratory failure. Compared with PEEP alone, LBPP increased cardiac index (CI) from 3.57 to 4.76 l X min-1 X m-2 (P less than 0.001) in relation to changes in right atrial pressure (RAP) (11 to 16 mmHg; P less than 0.01). Cardiopulmonary blood volume (CPBV) measured in five patients increased during LBPP from 546 +/- 126 to 664 +/- 150 ml (P less than 0.01), with a positive linear relationship between changes in RAP and CPBV (r = 0.88; P less than 0.001). Venous admixture (Qva/QT) decreased with PEEP from 24 to 16% (P less than 0.001) but did not change with LBPP despite the large increase in CI, leading to a marked O2 availability increase (P less than 0.001). Although PEEP induced a significant rise in plasma norepinephrine level (NE) (from 838 +/- 97 to 1008 +/- 139 pg/ml; P less than 0.05), NE was significantly decreased by LBPP to control level (from 1,008 +/- 139 to 794 +/- 124 pg/ml; P less than 0.003). Plasma epinephrine levels were not influenced by PEEP or LBPP. Changes of plasma renin activity (PRA) paralleled those of NE. No change in plasma arginine vasopressin (AVP) was recorded. We concluded that LBPP increases venous return and CPBV and counteracts hemodynamic effects of PEEP ventilation, without significant change in Qva/QT. Mechanical ventilation with PEEP stimulates sympathetic activity and PRA apparently by a reflex neuronal mechanism, at least partially inhibited by the loading of cardiopulmonary low-pressure reflex and high-pressure baroreflex. Finally, AVP does not appear to be involved in the acute cardiovascular adaptation to PEEP.     

Influence of brief high intensity exercise on plasma adrenaline and noradrenaline levels]

This study was conducted to determine catecholamine response to maximal intensity exercise of a few seconds' duration. To do this, epinephrine (E) and norepinephrine (NE) levels were measured during Force-Velocity Test. Blood samples were taken at the end of each sprint. Compared to rest (E0 = 77.4 +/- 3.8 pg/ml), the E concentration significantly increased after the first sprint (E2 = 109.8 +/- 14.7 pg/ml) and after the last one (E8 = 126.9 +/- 19.4 pg/ml) which correspond to the exhaustion state of our subjects. NE concentration doubled after the first sprint (NE2 = 589.1 +/- 94.7 pg/ml) and remained at this level until the end of the test. E2 seems to have been a stress reaction to an unfamiliar test. E8 may represent the "exercise plus exhaustion" stimulus on the stimulation of the adrenal gland (AG). This would suggest that stimulus intensity plays a role even when duration is very brief, although the time factor seems to limit the response of AG. The evolution of NE suggest that the brief duration of the sprints may limit the adatation response of NE to energy demands.     

Plasma vasopressin, neurophysin, renin and aldosterone during a 4-day head-down bed rest with and without exercise

The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is currently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (-6 degrees) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% VO2max) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.     

Contribution of adrenal norepinephrine output to increase aortic norepinephrine during carotid sinus reflex activation in anesthetized dogs

Changes in circulating plasma catecholamine (CA: E, epinephrine; NE, norepinephrine; and DA, dopamine) concentrations in aortic (AO) blood were investigated in relation to variable rates of CA secretion from both adrenal (ADR) glands in response to bilateral carotid artery occlusion (BLCO) in vagotomized dogs anesthetized with sodium pentobarbital. During BLCO (3 min), AO systolic pressure (AP) increased along with significant increases in ADR-CA output, renal venous (RV) CA output, as well as in AO-E and NE concentrations. A ratio of NE:E in ADR venous and AO blood did not exceed 0.42 +/- 0.09 and 1.09 +/- 0.24 upon BLCO, respectively. In contrast, the NE:E ratio in RV blood increased significantly from 5.39 +/- 0.91 to 9.78 +/- 1.31. Following adrenalectomy (ADRX), the increase in AO-NE in response to BLCO was significantly attenuated by approximately 56%, but the increase in RV-NE output was not affected by ADRX. The results show that in vagotomized dogs, NE is co-released with E from the adrenal glands upon BLCO. The data also indicate that the increase in AO-NE concentration was dependent to a similar extent on the simultaneous increases in ADR-NE output and neuronal NE release. We conclude that under conditions where the sympathoadrenal system is activated, circulating plasma NE concentration may be significantly affected by an increase in ADR-NE output. Sympathetic neuronal contributions would, thereby, be overestimated in assessing overall sympathetic nerve activity by measuring circulating NE. NE concentrations in local venous effluent from individual organs may be more reliable estimates of the sympathetic nerve activity.     

Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension

We studied vagally mediated carotid baroreceptor-cardiac reflexes in 11 healthy men before, during, and after 30 days of 6 degrees head-down bed rest to test the hypothesis that baroreflex malfunction contributes to orthostatic hypotension in this model of simulated microgravity. Sigmoidal baroreflex response relationships were provoked with ramped neck pressure-suction sequences comprising pressure elevations to 40 mmHg followed by serial R-wave-triggered 15-mmHg reductions to -65 mmHg. Each R-R interval was plotted as a function of systolic pressure minus the neck chamber pressure applied during the interval. Compared with control measurements, base-line R-R intervals and the minimum, maximum, range, and maximum slope of the R-R interval-carotid pressure relationships were reduced (P less than 0.05) from bed rest day 12 through recovery day 5. Baroreflex slopes were reduced more in four subjects who fainted during standing after bed rest than in six subjects who did not faint (-1.8 +/- 0.7 vs. -0.3 +/- 0.3 ms/mmHg, P less than 0.05). There was a significant linear correlation (r = 0.70, P less than 0.05) between changes of baroreflex slopes from before bed rest to bed rest day 25 and changes of systolic blood pressure during standing after bed rest. Although plasma volume declined by approximately 15% (P less than 0.05), there was no significant correlation between reductions of plasma volume and changes of baroreflex responses. There were no significant changes of before and after plasma norepinephrine or epinephrine levels before and after bed rest during supine rest or sitting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males

Although plasma norepinephrine (NE) increases with age in response to a variety of submaximal adrenergic stimuli, the effect of age on plasma catecholamine levels during maximal aerobic effort and during submaximal work at a fixed percent of peak O2 consumption (VO2) is unknown. We therefore measured NE, epinephrine (E), and VO2 at rest and during graded maximal treadmill exercise in 24 healthy male volunteers (ages 22-77 yr) from the Baltimore Longitudinal Study of Aging who were rigorously screened to exclude the presence of cardiovascular disease. At rest neither heart rate (HR) nor VO2 were age related. Resting NE (pg/ml) was not age related, but resting E (pg/ml) was higher in male subjects 68-77 yr old (group III) than in those aged 22-37 (group I) or 44-55 yr (group II), P less than 0.01. Maximal HR (beats/min) showed a strong inverse relationship to age (203.5 - 0.65 age, r = -0.80, P less than 0.001). Peak VO2 in milliliters per kilogram total body weight per minute decreased with age (47.7 - 0.23 age, r = -0.71, P less than 0.001). At maximal effort both NE (P less than 0.01) and E (P less than 0.05) were higher in group III than in either of the younger groups. At submaximal work levels NE and E also increased with age, and when normalized for relative effort at loads between 45 and 80% of peak VO2 both NE and E were higher in the group III male subjects, although statistical significance was reached for NE (P less than 0.01) but not for E (P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of core temperature as a stimulus for cold acclimation during repeated immersion in 20 degrees C water.

The relative importance of skin vs. core temperature for stimulating cold acclimation (CA) was examined by 5 wk of daily 1-h water immersions (20 degrees C) in resting (RG) and exercising (EG) subjects. Rectal temperature fell (0.8 degrees C; P < 0.05) during immersion only in RG. Skin temperature fell (P < 0.05) similarly in both groups. Physiological responses during cold-air exposure (90 min, 5 degrees C) were assessed before and after CA. Body temperatures and metabolic heat production were similar in both groups with no change due to CA. Cardiac output was lower (P < 0.05) in both groups post-CA (10.4 +/- 1.2 l/min) than pre-CA (12.2 +/- 1. 0 l/min), but mean arterial pressure was unchanged (pre-CA 107 +/- 2 mmHg, post-CA 101 +/- 2 mmHg). The increase in norepinephrine was greater (P < 0.05) post-CA (954 +/- 358 pg/ml) compared with pre-CA (1,577 +/- 716 pg/ml) for RG, but CA had no effect on the increase in norepinephrine for EG (pre-CA 1,288 +/- 438 pg/ml, post-CA 1,074 +/- 279 pg/ml). Skin temperature reduction alone may be a sufficient stimulus during CA for increased vasoconstrictor response, but core temperature reduction appears necessary to enhance sympathetic activation during cold exposure.     

Suppressing lipolysis increases interleukin-6 at rest and during prolonged moderate-intensity exercise in humans.

IL-6 induces lipolysis when administered to humans. Consequently, it has been hypothesized that IL-6 is released from skeletal muscle during exercise to act in a "hormonelike" manner and increase lipolysis from adipose tissue to supply the muscle with substrate. In the present study, we hypothesized that suppressing lipolysis, and subsequent free fatty acid (FFA) availability, would result in a compensatory elevation in IL-6 at rest and during exercise. First, we had five healthy men ingest nicotinic acid (NA) at 30-min intervals for 120 min at rest [10 mg/kg body mass (initial dose), 5 mg/kg body mass (subsequent doses)]. Plasma was collected and analyzed for FFA and IL-6. After 120 min, plasma FFA concentration was attenuated (0 min: 0.26 +/- 0.05 mmol/l; 120 min: 0.09 +/- 0.02 mmol/l; P < 0.01), whereas plasma IL-6 was concomitantly increased approximately eightfold (0 min: 0.75 +/- 0.18 pg/ml; 120 min: 6.05 +/- 0.89 pg/ml; P < 0.001). To assess the effect of lipolytic suppression on the exercise-induced IL-6 response, seven active, but not specifically trained, men performed two experimental exercise trials with (NA) or without [control (Con)] NA ingestion 60 min before (10 mg/kg body mass) and throughout (5 mg/kg body mass every 30 min) exercise. Blood samples were obtained before ingestion, 60 min after ingestion, and throughout 180 min of cycling exercise at 62 +/- 5% of maximal oxygen consumption. IL-6 gene expression, in muscle and adipose tissue sampled at 0, 90, and 180 min, was determined by using semiquantitative real-time PCR. IL-6 mRNA increased in Con (rest vs. 180 min; P < 0.01) approximately 13-fold in muscle and approximately 42-fold in fat with exercise. NA increased (rest vs. 180 min; P < 0.01) IL-6 mRNA 34-fold in muscle, but the treatment effect was not statistically significant (Con vs. NA, P = 0.1), and 235-fold in fat (Con vs. NA, P < 0.01). Consistent with the study at rest, NA completely suppressed plasma FFA (180 min: Con, 1.42 +/- 0.07 mmol/l; NA, 0.10 +/- 0.01 mmol/l; P < 0.001) and increased plasma IL-6 (180 min: Con, 9.81 +/- 0.98 pg/ml; NA, 19.23 +/- 2.50 pg/ml; P < 0.05) during exercise. In conclusion, these data demonstrate that circulating IL-6 is markedly elevated at rest and during prolonged moderate-intensity exercise when lipolysis is suppressed.