Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man

Bg, Wallin; Sundlöf, G; Bm, Eriksson; Dominiak, Peter; Grobecker, H.; Le, Lindblad

doi:10.1111/j.1748-1716.1981.tb06706.x

Cited by 305 publications

(109 citation statements)

References 18 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indications in this direction come from a report where a smaller increase in plasma NA, after an oral glucose load, was shown in obese diabetic patients. 21 Basal sympathetic activity, as re¯ected by basal plasma NA concentrations, 22 has been reported to be depressed in diabetic obese patients. 21 Although plasma NA concentrations were lower in NIDDM compared to CON, this difference did not reach statistical signi®cance.…”

Section: Discussionmentioning

confidence: 99%

Substrate utilization and thermogenic responses to β-adrenergic stimulation in obese subjects with NIDDM

Blaak

Wolffenbuttel

1999

Int J Obes

View full text Add to dashboard Cite

OBJECTIVE: This study intended to investigate disturbances in b-adrenergically-mediated substrate utilization and thermogenesis in obese subjects with mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the b-agonist isoproterenol (ISO) was administered in increasing doses of 6, 12, and 24 ngakg FFM .min, each dose for 30 min. SUBJECTS: Nine healthy lean males (CON, 50.6 AE 2.4 y, % body fat: 16.0 AE 1.8) and 10 obese subjects with NIDDM (51.8 AE 2.4 y, % body fat 34.1 AE 1.9). RESULTS: Basal non esteri®ed fatty acid concentrations (NEFA) and basal fat oxidation (absolute or expressed per unit fat free mass, FFM) were signi®cantly higher in NIDDM as compared to CON, whereas basal carbohydrate (CHO) oxidation was signi®cantly lower. The ISO-induced increase in NEFA-concentrations was blunted in NIDDM (D at 24 ngakg FFM .min: CON: 717 AE 59 mmolal vs NIDDM: 358 AE 97 mmolal, P`0.01). The non-protein respiratory exchange ratio (RER) did not change in NIDDM and signi®cantly decreased in CON during ISO-infusion (P`0.05), re¯ecting the tendency towards a blunted increase in fat oxidation in NIDDM (D fat ox at 24 ng; CON: 0.025 AE 0.005 gamin vs NIDDM 0.016 AE 0.007 gamin). The ISO-induced thermogenic response was comparable in NIDDM and CON (at 24 ng %increase above baseline: CON: 16.8 AE 2.2% vs NIDDM: 14.7 AE 0.9%). At all time points, there were no signi®cant differences in circulating ISO and noradrenaline concentrations. Basal adrenaline (A) concentrations and A concentrations during ISO-infusion were signi®cantly lower in NIDDM (basal A; CON: 64 AE 15 pgaml vs NIDDM: 25 AE 2 pgaml, P`0.001). CONCLUSION: There appear to be deviations in b-adrenoceptor mediated fat utilization and adrenal medulla function in obesity-associated NIDDM. The impairments in sympathetically mediated fat utilization have previously been observed in`simple' obese subjects, indicating that these disturbances are con®ned to the obese state per se.

show abstract

Section: Discussionmentioning

confidence: 99%

Substrate utilization and thermogenic responses to β-adrenergic stimulation in obese subjects with NIDDM

Blaak

Wolffenbuttel

1999

Int J Obes

View full text Add to dashboard Cite

show abstract

“…Direct measurement of muscle sympathetic nerve activity. Muscle sympathetic nerve activity (MSNA) was recorded from the peroneal nerve at the level of the fibular head and popliteal fossa (16,17). The approximate location of this nerve was determined by transdermal electrical stimulation to produce painless muscle contraction of the foot.…”

Section: Methodsmentioning

confidence: 99%

Effects of a Selective Serotonin Reuptake Inhibitor, Fluoxetine, on Counterregulatory Responses to Hypoglycemia in Healthy Individuals

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Hypoglycemia commonly occurs in intensivelytreated diabetic patients. Repeated hypoglycemia blunts counterregulatory responses, thereby increasing the risk for further hypoglycemic events. Currently, physiologic approaches to augment counterregulatory responses to hypoglycemia have not been established. Therefore, the specific aim of this study was to test the hypothesis that 6 weeks' administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine would amplify autonomic nervous system (ANS) and neuroendocrine counterregulatory mechanisms during hypoglycemia. RESEARCH DESIGN AND METHODS-A total of 20 healthy (10 male and 10 female) subjects participated in an initial single-step hyperinsulinemic (9 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 )-hypoglycemic (means Ϯ SE 2.9 Ϯ 0.1 mmol/l) clamp study and were then randomized to receive 6 weeks' administration of fluoxetine (n ϭ 14) or identical placebo (n ϭ 6) in a double-blind fashion. After 6 weeks, subjects returned for a second hypoglycemic clamp. Glucose kinetics were determined by three-tritiated glucose, and muscle sympathetic nerve activity (MSNA) was measured by microneurography.RESULTS-Despite identical hypoglycemia (2.9 Ϯ 0.1 mmol/l) and insulinemia during all clamp studies, key ANS (epinephrine, norepinephrine, and MSNA but not symptoms), neuroendocrine (cortisol), and metabolic (endogenous glucose production, glycogenolysis, and lipolysis) responses were increased (P Ͻ 0.01) following fluoxetine.CONCLUSIONS-This study demonstrated that 6 weeks' administration of the SSRI fluoxetine can amplify a wide spectrum of ANS and metabolic counterregulatory responses during hypoglycemia in healthy individuals. These data further suggest that serotonergic transmission may be an important mechanism in modulating sympathetic nervous system drive during hypoglycemia in healthy individuals. Diabetes 57:2453-2460, 2008 S everal reports have indicated that fluoxetine could have metabolic effects and influence carbohydrate metabolism (1-3). In fact, there have been three case studies reporting the occurrence of hypoglycemia related to the use of selective serotonin reuptake inhibitors (SSRIs) in depressed patients with and without diabetes (4 -6). However, although SSRIs are potent inhibitors of neuronal serotonin uptake, they also have the ability to block norepinephrine transport (7). This could increase sympathetic outflow activity (2,8). Baudrie and Chaouloff (9) have previously reported an increased hyperglycemic response to 2-deoxy-D-glycose in conscious rats following serotononergic receptor antagonists, implying increased counterregulation in these animals.A subsequent study by Perry and Fuller (2) demonstrated that systemic injection of the SSRI fluoxetine in rats resulted in threefold increases of hypothalamic norepinephrine release, thereby providing a mechanistic basis for SSRIs to modulate sympathetic nervous system activity. A later study by Bymaster et al. (3) examined the specificity of five different SSRIs (fluoxetine, citalopram, fluvoxamine, paroxe...

show abstract

“…Selective increases in cardiac, renal, or splanchnic sympathetic nerve activity could initiate marked hemodynamic changes in hypertensive persons without altering basal venous PNE concentrations, because of hepatic clearance of catecholamines, 22 regional differences in the vascular response to released norepinephrine, or quantitative differences in the adrenergic innervation to these vascular beds. Indeed, PNE correlates well with efferent sympathetic nerve activity to muscle, 23 an organ unlikely to be involved in the pathogenesis of hypertension. Thus, changes in PNE might not always reflect changes in sympathetic tone or reveal a neurogenic contribution to essential hypertension.…”

mentioning

confidence: 99%

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans.

Floras¹,

Jones²,

Hassan³

et al. 1986

Hypertension

View full text Add to dashboard Cite

SUMMARY To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on infra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 ± 18 to 127 ± 18 mm Hg (mean ± S.D.; p<0.001) and heart rate from 69 ± 7 to 93 ± 13 beats/min (p<0.001) but not plasma norepinephrine (547 ± 297 to 518 ± 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 ± 18 to 148 ± 21 mm Hg (p<0.001) and heart rate from 76 ± 9 to 95 ± 13 beats/min (p<0.001) but not plasma norepinephrine (683 ± 253 to 741 ± 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 ± 20 to 146 ± 26 mm Hg (p< 0.001), heart rate from 77 ± 9 to 128 ± 19 beats/min (p< 0.001), and plasma norepinephrine from 645 ± 228 to 1151 ± 462 pg/ml (p<0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p<0.02 and r=0.28, p<0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects. In fact, the relative rise in mean arterial pressure and the absolute increase in plasma norepinephrine during cycling were greater in those with lower resting blood pressures. As only bicycle exerdse increased plasma norepinephrine, and as there was no direct relationship between plasma norepinephrine and arterial blood pressure in subjects studied supine, seated, and during these three activities, we conclude that plasma norepinephrine concentrations do not consistently reflect variations in sympathetic neuronal activity and therefore are relatively insensitive measures of sympathetic tone in humans. Received March 25, 1985; accepted January 21, 1986. Norepinephrine concentration in the venous drainage of an organ is also proportional to the rate of stimulation of its nerves. 3 In humans, physical and emotional stimuli that increase blood pressure and heart rate (HR) also increase PNE. "7 Conversely, concentrations of this catecholamine may be reduced in subjects with autonomic nervous dysfunction 8 or lowered by drugs that interfere with the action of the sympathetic nervous system. 9 Watson et al., 6 who recorded PNE and blood pressure in hypertensive subjects while they slept, lay quietly, woke, stood, walked, and cycled, described a log-linear relationship between PNE and systolic blood pressure during these activities, which suggests that PNE concentrations indeed reflect changes in sympathetic activity.Although increases in PNE with exertion may be greater in some subjects with essential hypertension, 10

show abstract

Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man

Cited by 305 publications

References 18 publications

Substrate utilization and thermogenic responses to β-adrenergic stimulation in obese subjects with NIDDM

Substrate utilization and thermogenic responses to β-adrenergic stimulation in obese subjects with NIDDM

Effects of a Selective Serotonin Reuptake Inhibitor, Fluoxetine, on Counterregulatory Responses to Hypoglycemia in Healthy Individuals

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans.

Contact Info

Product

Resources

About