Sympathetic nervous activity and the thermic effect of food in humans.
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Body Temperature Regulation↗
Biomedical subjects
M D Esler
Publications and source records attributed to M D Esler.
Human muscle sympathetic activity and cardiac catecholamine spillover: no support for augmented sympathetic noradrenaline release by adrenaline co-transmission.
1. Evidence from animal studies indicates that circulating adrenaline may be taken up into sympathetic nerves, facilitating the release of noradrenaline. To test whether adrenaline acts as a co-transmitter in humans we studied eight healthy men (aged 19-23 years) during isometric handgrip before and after an adrenaline infusion (1-3 micrograms/min for > 30 min). Sympathetic activity was assessed using radiotracer kinetic techniques to measure total and cardiac spillovers of noradrenaline and adrenaline, and microneurography to measure muscle sympathetic activity. 2. During the adrenaline infusion systolic blood pressure and heart rate increased significantly and diastolic blood pressure decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma noradrenaline concentrations, increased significantly. Muscle sympathetic nerve traffic increased both during and after the end of the infusion. 3. Thirty minutes after the end of the adrenaline infusion there was adrenaline release from the heart (1.5 +/- 0.4 ng/min, mean +/- S.E.M.) indicating that significant adrenaline loading of cardiac sympathetic nerves had occurred. At this time muscle sympathetic nerve traffic and total body and cardiac noradrenaline spillovers were similar (P > 0.05) to pre-adrenaline infusion values (nerve traffic 24 +/- 4 versus 21 +/- 3 bursts/min; total noradrenaline spillover 698 +/- 98 versus 618 +/- 119 ng/min; cardiac noradrenaline spillover 16.2 +/- 2.8 versus 13.9 +/- 3.9 ng/min). 4. Isometric handgrip contraction evoked similar responses pre- and post-adrenaline infusion in total and cardiac noradrenaline spillovers and in muscle sympathetic activity. 5. The results do not support the theory that adrenaline is a co-transmitter facilitating noradrenaline release from human sympathetic nerves.
Adult↗
Control of the forearm microcirculation: interactions with measures of obesity and noradrenaline kinetics.
1. Obesity influences the responsiveness of the microcirculation; constriction is augmented probably reflecting heightened sympathetic nervous activity. 2. The responsiveness of the microcirculation in the forearm to constriction and dilation was therefore examined in 14 men and women with varying degrees of abdominal adiposity, to determine the potential effects of sympathetic nervous activity and adiposity on flow. Changes in basal blood flow were measured by venous occlusion plethysmography during intra-arterial infusions of noradrenaline, acetylcholine and sodium nitroprusside and after temporary ischaemia. Total body noradrenaline spillover was also measured, as an index of sympathetic neuronal activity. 3. Parameters of obesity were found to influence the responsiveness of the microcirculation. Changes in vascular resistance with noradrenaline (100 ng/min) were positively correlated with body weight, body mass index and waist circumference (r=0.63, P=0.02), whereas waist circumference was negatively correlated with post-ischaemia vasodilatation (r=-0.76, P=0.002). Acetylcholine-induced vasodilatation was inversely related to body mass index (r=-0.53, P=0.053). 4. Basal blood flow did not correlate with adiposity. Furthermore, vasodilatation with 800 ng/min sodium nitroprusside was inversely correlated with total body noradrenaline spillover (r=-0. 77, P<0.001); and changes in flows with noradrenaline (constriction) and post-ischaemia (dilation) were inversely related (r=-0.56, P=0. 035). 5. These findings, taken together, are consistent with increased local sympathetic neuronal responsiveness and diminished nitric-oxide-mediated dilation in the forearm vasculature with increasing body adiposity.
Acetylcholine↗
Internal jugular venous spillover of noradrenaline and metabolites and their association with sympathetic nervous activity.
It is recognized that the brain plays a pivotal role in the maintenance of blood pressure and the control of myocardial function. By combining direct sampling of internal jugular venous blood with a noradrenaline isotope dilution method, for examining neuronal transmitter release, and microneurographic nerve recording, we were able to quantify the release of central nervous system noradrenaline and its metabolites and investigate their association with efferent sympathetic nervous outflow in healthy subjects and patients with pure autonomic failure. To further investigate the relationship between brain noradrenaline, sympathetic nervous activity and blood pressure regulation we examined brain catecholamine turnover, based on the internal jugular venous overflow of noradrenaline and its principal central nervous system metabolites, in response to a variety of pharmacological challenges. A substantial increase was seen in brain noradrenaline turnover following trimethaphan, presumably resulting from a compensatory response in sympathoexcitatory forebrain noradrenergic neurones in the face of interruption of sympathetic neural traffic and reduction in arterial blood pressure. In contrast, reduction in central nervous system noradrenaline turnover accompanied the blood pressure fall produced by intravenous clonidine administration, thus representing the blood pressure lowering action of the drug. Following vasodilatation elicited by intravenous adrenaline infusion, brain noradrenaline turnover increased in parallel with elevation in muscle sympathetic nervous activity. While it is difficult to assess the source of the noradrenaline and metabolites determined in our studies, available evidence implicates noradrenergic cell groups of the posterolateral hypothalamus, amygdala, the A5 region and the locus coeruleus as being involved in the regulation of sympathetic outflow and autonomic cardiovascular control.
Adolescent↗
Depression of efferent parasympathetic control of heart rate in rats with myocardial infarction: effect of losartan.
Heart failure is associated with attenuation of parasympathetic nervous function and enhanced renin-angiotensin activity. We tested whether there was a dysfunction in the efferent cholinergic neurotransmission in the heart of rats with chronic myocardial infarction (MI) and the potential role of angiotensin II (Ang II) receptors in such changes. Rats with MI and sham-operation were anesthetized, and heart rate (HR) reduction in response to vagal nerve stimulation was measured before and after losartan administration (10 mg/kg, i.v.) in the presence or absence of physostigmine to inhibit acetylcholinesterase. Infarcted rats had an average infarct size (IS) of 38% of the left ventricle (LV), depressed LV dP/dtmax, elevated LVEDP, and cardiac hypertrophy. Nerve stimulation (1-16 Hz) reduced HR in a frequency-dependent manner. The bradycardiac responses were significantly attenuated in infarcted versus control rats (p < 0.01), indicating an impaired efferent vagal tone. In contrast, the bradycardic response to exogenous acetylcholine was similar in both groups, implying an unchanged muscarinic receptor responsiveness in hearts with MI. HR response to nerve stimulation was potentiated by losartan in infarcted rats by 21 +/- 4 versus 4 +/- 2 beats/min (p < 0.01) but was unaffected in control rats. This effect of losartan was inversely related to the extent of attenuation of vagally mediated HR reduction. IS was correlated with both the extent of attenuation in vagally mediated bradycardia and the effect of losartan. In conclusion, the efferent vagal control of HR is attenuated in rats with MI and heart failure. This attenuation may be partly due to a presynaptic inhibition of acetylcholine release through the tonic activation, by Ang II, of neuronal AT1 receptors.
Acetylcholine↗
Protection of neuronal uptake-1 inhibitors in ischemic and anoxic hearts by norepinephrine-dependent and -independent mechanisms.
Cardiac ischemia and anoxia induce massive norepinephrine (NE) release, which is mediated by a reverse operation of uptake-1 and can be suppressed by uptake-1 inhibitors. We studied effects of uptake-1 inhibitors on incidence of ventricular fibrillation (VF%) and myocardial contracture in perfused rat hearts under ischemic or anoxic conditions. NE release occurred in hearts during ischemia or anoxia and was largely inhibited by desipramine, imipramine, and cocaine. The generation of inositol 1,4,5-trisphosphate (InsP3) during reperfusion also was abolished by desipramine. During anoxia/reoxygenation, VF (93 and 71%, respectively) and myocardial contracture occurred and were significantly inhibited by desipramine and by NE depletion. Regional ischemia and reperfusion induced high VF% (86 and 100%, respectively), which was reduced or abolished by desipramine and imipramine at 0.03 and 0.3 microM. During the ischemic phase, cocaine was similarly antiarrhythmic, as was a combination of timolol and prazosin, but NE depletion was not. In NE-depleted hearts, cocaine or the combination of timolol and prazosin showed limited effect on VF%, whereas both desipramine and imipramine abolished VF. In anesthetized rats in vivo, ischemic VF% was reduced by desipramine (30 vs. 92%; p < 0.01). In conclusion, uptake-1 inhibitors protect hearts against ischemia/reperfusion- and anoxia/reoxygenation-induced arrhythmias, partly because of the inhibition of locally mediated NE release. Other actions of desipramine and imipramine may contribute to the overall efficacy.
Adrenergic Uptake Inhibitors↗
Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans.
Continuous release of nitric oxide contributes to the maintenance of resting tone in the human forearm and coronary circulations; however, evidence for a similar role of vasodilator prostanoids such as prostacyclin is lacking. We examined whether continuous release of prostacyclin contributes to basal forearm blood flow. Flow was measured using venous occlusion plethysmography in 38 healthy volunteers [mean age 21.3 +/- 2.5 yr (+/- SD); 13 female, 25 male] at rest, after administration of three incremental intra-arterial infusions of either the cyclooxygenase inhibitor aspirin or placebo, and before and after administration of the endothelium-dependent and -independent dilators acetylcholine (30 micrograms/min) and nitroprusside (1 microgram/min). To assess the effect of aspirin on the production of prostacyclin, plasma 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha; the stable metabolite of prostacyclin) was measured by simultaneous arterial and venous sampling. Aspirin produced a time- and dose-dependent reduction in forearm blood flow, resulting in a 32% decrease at the highest dose. The effect was maximal after 10 min. Flow at rest and after aspirin doses of 1, 3, and 10 mg/min was 2.6 +/- 0.2, 2.3 +/- 0.2, 2.1 +/- 0.2, and 1.8 +/- 0.2 ml.100 ml forearm tissue-1.min-1, respectively (means +/- SE, P < 0.001). Commensurate with these data, the net forearm production of 6-keto-PGF1 alpha was 52.9 +/- 16.4, 11.7 +/- 8.6, 18.7 +/- 8.5, and 12.0 +/- 12.5 pg.100 ml forearm tissue-1.min-1 for the respective doses (P = 0.04). No time-dependent reduction in flow was seen in subjects with vehicle infusion. Aspirin did not affect the responses to acetylcholine or nitroprusside. These data suggest that continuous release of prostacyclin plays a role in the maintenance of resting forearm blood flow. There appears to be a direct link between the reduction in flow with aspirin and inhibition of prostacyclin production.
6-Ketoprostaglandin F1 alpha↗
Cerebral noradrenaline spillover and its relation to muscle sympathetic nervous activity in healthy human subjects.
Studies using internal jugular vein blood sampling in human subjects have demonstrated the release of noradrenaline from the brain and have provided a link between central nervous system noradrenergic neuronal activity and renal, cardiac and total body sympathetic activity. The aim of this study was to further categorise the dependence of regional sympathetic nervous function on central nervous system noradrenergic neuronal processes by combining measures of internal jugular venous noradrenaline spillover, as an indicator of brain noradrenaline release, and cerebral blood flow scans with measures of the overall integrated neuronal firing rate for the body as a whole, the spillover of noradrenaline into the coronary sinus and with measurements of resting muscle sympathetic nerve activity. Positive veno-arterial plasma noradrenaline gradients were found across the brain, with the plasma concentration being 17 +/- 3% (p < 0.01) greater in the internal jugular vein. Linear regression analysis revealed a significant relationship between the degree of muscle sympathetic nerve activity and the spillover of noradrenaline from subcortical brain regions (y = 0.1 x + 16.0; r = 0.81, p < 0.02). The rate of spillover of noradrenaline for the body as a whole also bore a significant association with the rate of subcortical noradrenaline spillover (y = 0.01x + 2.33; r = 0.71, p < 0.05). Cortical noradrenaline spillover was not related to any of the sympathetic nervous system parameters measured in this study. The demonstration of a direct relationship between the rate of peroneal nerve firing and the spillover of noradrenaline from subcortical brain regions provides further support for the concept of central nervous system noradrenergic cell groups behaving in a sympathoexcitatory role.
Adult↗
Effects of intracellular Ca2+ chelating on noradrenaline release in normoxic and anoxic hearts.
1. Ischaemia and anoxia induce excessive noradrenaline (NA) release in the heart by a mechanism independent of both nerve activity and extracellular Ca2+. The present study was designed to examine the potential role of intracellular Ca2+ mobilization in anoxic NA release in the heart by chelating intracellular free Ca2+. 2. In normoxic hearts, preloading with an intracellular free Ca2+ chelator (BAPTA) reduced neuronal NA release by 65%, confirming the effectiveness of the loading protocol. Release of NA independent of nerve activity occurred in hearts subjected to a 40 min period of anoxic, substrate-free and nominal Ca(2+)-free perfusion. Loading hearts with BAPTA prior to anoxia failed to reduce NA overflow (1561 +/- 147 vs 1496 +/- 206 pmol/g over 40 min). Infusion with BAPTA (20 mumol/L) during the first 25 min of the anoxic period reduced the quantity of anoxic NA release by approximately 25% from 2013 +/- 124 to 1476 +/- 207 pmol/g (P < 0.05). 3. Our results confirm that anoxic NA release is predominantly a Ca(2+)-independent process with Ca2+ mobilization from endogenous storage playing only a minor contributing role.
Animals↗
Pulmonary clearance and release of norepinephrine and epinephrine in newborn lambs.
To examine the pulmonary kinetics of the catecholamines norepinephrine and epinephrine immediately after birth, eight fetal lambs were instrumented with vascular catheters under general anesthesia at 133-134 days gestation (term = 147 days) and were delivered by cesarean section 1 wk later. Pulmonary norepinephrine and epinephrine kinetics were then studied 1 and 4 h after birth using radiotracer dilution methodology. The pulmonary fractional extraction of norepinephrine was similar in 1-h (0.111 +/- 0.021) and 4-h (0.117 +/- 0.023) lambs and constituted 24 +/- 5 and 32 +/- 9% of total body norepinephrine clearance, respectively. Pulmonary removal of epinephrine was less pronounced with a fractional extraction of 0.035 +/- 0.017 in 1-h and 0.036 +/- 0.013 in 4-h lambs, which corresponded to 8 +/- 4 and 9 +/- 3% of total body epinephrine clearance, respectively. Pulmonary spillover of norepinephrine into the circulation was similar in 1-h (79 +/- 26 ng.min-1.kg-1) and 4-h (82 +/- 18 ng.min-1.kg-1) lambs, and this comprised 27 +/- 8 and 42 +/- 8% of total body norepinephrine spillover, respectively. Pulmonary epinephrine spillover was not detectable at 1 h, but it occurred in all 4-h lambs, averaging 4.7 +/- 0.8 ng.min-1.kg-1 or 20 +/- 6% of epinephrine total body spillover. These findings indicate that the lungs of newborn lambs 1) are a major site for removal of norepinephrine and epinephrine from the circulation; 2) release a substantial quantity of norepinephrine into the circulation, consistent with the presence of tonic pulmonary sympathetic nerve activity; and 3) constitute a significant extra-adrenal source of plasma epinephrine.
Animals↗
Region-specific neuropeptide Y overflows at rest and during sympathetic activation in humans.
Neuropeptide Y coexists with norepinephrine in sympathetic nerves and is coreleased into the circulation on sympathetic activation. Little is known about the regional release of neuropeptide Y in humans under normal conditions or in pathophysiological situations of sympathetic activation or denervation. We measured plasma neuropeptide Y-like immunoreactivity and norepinephrine concentrations in samples taken from the brachial artery; coronary sinus; and internal jugular, antecubital, or hepatic veins in volunteers aged 20 to 64 years. Regional neuropeptide Y overflow at rest was calculated from venoarterial plasma concentration differences and plasma flow, and norepinephrine spillover was determined by [3H]norepinephrine infusion techniques. Cardiac release of neuropeptide Y and norepinephrine was examined in response to various stressors as well as in clinical models of sympathetic activation, cardiac failure, and denervation after cardiac transplantation. In healthy volunteers, cardiac, forearm, and jugular venous sample neuropeptide Y concentrations were similar to arterial levels. Hepatic vein plasma neuropeptide Y was greater than arterial both at rest (119 +/- 5% of arterial, n = 7) and after a meal (132 +/- 12%, n = 7), with neuropeptide Y overflows of 6 +/- 2 and 11 +/- 2 pmol/min, respectively. In contrast, hepatomesenteric norepinephrine spillover was not significantly increased by feeding. Although coronary sinus plasma norepinephrine concentrations increased significantly with the cardiac sympathetic activation accompanying mental arithmetic, coffee drinking, isotonic exercise, and bicycle exercise, only the latter powerful sympathetic stimulus increased neuropeptide Y overflow. Cardiac failure was associated with increased resting release of both norepinephrine and neuropeptide Y from the heart, whereas postcardiac transplant norepinephrine spillover from the heart was reduced. The net overflow of neuropeptide Y to plasma observed at rest across the hepatic circulation, but not the cardiac, forearm, or cerebral circulations, indicates that the gut, the liver, or both make a major contribution to systemic plasma neuropeptide Y levels in humans. Sympathetic activation by exercise produced a modest increase in cardiac neuropeptide Y overflow but to only approximately 25% of the resting input from the gut and without a change in arterial neuropeptide Y concentration. Plasma neuropeptide Y measurements are less sensitive than those of plasma norepinephrine concentrations as an index for quantifying sympathetic neural responses regulating the systemic circulation.
Adult↗
Role of Ca2+ in metabolic inhibition-induced norepinephrine release in rat brain synaptosomes.
Ischemia and simulated ischemic conditions induce enhanced release of norepinephrine (NE) in the brain and the heart. Although studies with neuronal preparations demonstrated a rise in [Ca2+]i under energy-depleted conditions, such release of NE in the heart appears to be predominantly Ca2+ independent. Since Ca2+ overload occurs in ischemia or energy depletion and since a rise in [Ca2+]i triggers exocytosis without membrane depolarization, we tested the possibility, using brain synaptosomes, that increased NE release could be, at least in part, a consequence of raised [Ca2+]i. Brain synaptosomes were incubated with Krebs-Henseleit medium, and ischemia was mimicked by treatment with metabolic inhibitors. NE content in incubation medium (supernatant) and synaptosomes was analyzed chromatographically. Treatment with metabolic inhibitors reduced ATP content by 75% and increased [Ca2+]i by more than fourfold within minutes. Metabolic inhibition elicited NE release, which started within 10 minutes and reached a maximum after 30 minutes, with a corresponding 55% reduction in synaptosomal NE content after 40 minutes. NE release, together with a marked increase in [Ca2+]i, was also induced in energy-depleted synaptosomes by Ca2+ repletion after incubation with the Ca(2+)-free medium. Effects on NE release of various interventions to prevent Ca2+ overload were tested. Omission of Ca2+ from the incubation medium or loading synaptosomes with the Ca2+ chelator BAPTA-AM (20 and 100 mumol/L) prevented NE release, indicating a Ca(2+)-dependent mechanism. Inhibition of Ca2+ channels with omega-conotoxin, cadmium, or nifedipine had no effect on NE release during energy depletion. In contrast, nickel and 3,4-dichlorobenzamil, Na(+)-Ca2+ exchange inhibitors, dose-dependently inhibited NE release. In conclusion, this study provides evidence that under energy-depleted conditions, Ca2+ overload in synaptosomes of noradrenergic neurons from the brain is an important mechanism for the enhanced release of NE and that a reversal of Na(+)-Ca2+ exchange may be the key pathway leading to intraneuronal Ca2+ overload.
Animals↗
Left ventricular norepinephrine and epinephrine kinetics at birth in lambs.
Little is known about the changes in the left ventricular (LV) kinetics of the catecholamines norepinephrine and epinephrine occurring at birth and their relationship to perinatal alterations in LV function and whole-body catecholamine kinetics. To address this issue, whole-body and LV catecholamine kinetics (radiotracer dilution methodology) and fetal LV output and myocardial blood flow (radioactive microspheres) were measured in chronically instrumented near-term fetuses and in the same animals 1 and 4 hours after birth. Between fetal and 1-hour lambs, LV external work increased 115% (P<.005); carotid arterial plasma norepinephrine concentration, 148% (P<.01); carotid arterial plasma epinephrine concentration, 546% (P<.005); LV norepinephrine spillover, a measure of LV sympathetic activity, 4.1-fold (P<.005); LV epinephrine spillover, 3-fold (P<.05); total-body spillover of norepinephrine, 52% (P<.025); and total-body spillover of epinephrine, 460% (P<.005). Arterial catecholamine concentrations and total-body catecholamine spillovers were unchanged between 1- and 4-hour lambs, but LV external work fell (P<.05) to a level still 77% greater than in fetal lambs (P<.005); LV norepinephrine spillover returned to near-fetal levels, and LV epinephrine spillover became undetectable. These results suggest that (1) a transient increase in LV sympathetic activity occurs at birth and may contribute to the immediate postnatal augmentation of LV performance, (2) organ differences in the pattern of sympathetic activation occur at birth, and (3) birth-related increases in LV sympathetic activity are accompanied by release of epinephrine from the heart.
Animals↗
Cardiac sympathetic nerve function in congestive heart failure.
BACKGROUND: Increased availability of norepinephrine (NE) for activation of cardiac adrenoceptors (increased cardiac adrenergic drive) and depletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a comprehensive neurochemical approach to examine the mechanisms responsible for these abnormalities. METHODS AND RESULTS: Subjects with and without congestive heart failure received intravenous infusions of [(3)H]NE. Cardiac spillover, reuptake, vesicular-axoplasmic exchange, and tissue stores of NE were assessed from arterial and coronary venous plasma concentrations of endogenous and [(3)H]-labeled NE and dihydroxyphenylglycol. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the efficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Cardiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillover of dopa and NE turnover were increased similarly in congestive heart failure. CONCLUSIONS: Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive in congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.
Adolescent↗
Renal noradrenaline spillover correlates with muscle sympathetic activity in humans.
1. To study the relationship between indices of resting sympathetic traffic in nerves to skeletal muscles and the kidneys, simultaneous measurements were made of muscle sympathetic activity in the peroneal nerve and renal noradrenaline spillover in ten healthy normotensive males aged 18-69 years (mean 42 years). 2. Group mean levels (+/-S.D.) of muscle sympathetic activity and renal spillover were 22 +/- 17 bursts min-1 and 105 +/- 49 ng min-1, respectively. There were significant positive correlations between individual values of muscle sympathetic activity and renal noradrenaline spillover (r = 0.76, P < 0.01) and similarly between muscle sympathetic activity and renal venous plasma concentration of noradrenaline(r = 0.79, P < 0.007). 3. The results indicate that, although the sympathetic system has the capacity for selective activation of different subdivisions, in healthy human subjects resting traffic is similar or proportional in sympathetic nerves to skeletal muscles and the kidney.
Adult↗
Oxygen consumption in the heart, hepatomesenteric bed, and brain in young and elderly human subjects, and accompanying sympathetic nervous activity.
Although the reduction in whole-body energy expenditure with aging has been well documented, there is little information about the changes that individual organs undergo. We therefore measured oxygen consumption in the heart, hepatomesenteric bed, and brain in elderly subjects and young controls, using central venous catheter techniques and the application of Fick's principle. We also measured whole-body, cardiac, and hepatomesenteric sympathetic nervous activity using isotope dilution methodology. Cardiac, hepatomesenteric, and cerebral oxygen consumption was similar in both groups. Whole-body and hepatomesenteric sympathetic nervous activity was also similar in the study groups, whereas cardiac norepinephrine (NE) spillover was significantly higher in the elderly. In contrast to the young, cardiac sympathetic nervous activity as assessed from NE spillover was not related to either cardiac oxygen consumption or cardiac work in the elderly. The data suggest that although oxygen consumption in the heart, hepatomesenteric bed, and brain are not different between young and elderly individuals, the relationship between sympathetic nervous activity and oxygen consumption in individual organs may alter with aging.
Adult↗
Increased spillover and reduced clearance both contribute to rise in plasma catecholamines after birth in lambs.
We studied the relationship between changes in norepinephrine (NE) and epinephrine (Epi) levels, total body spillover, and total body clearance at birth. Near-term fetal lambs were chronically instrumented under general anesthesia with arterial, venous, and left atrial catheters. One week later, NE and Epi kinetics (isotope dilution methodology) and systemic blood flows (radioactive microspheres) were measured in fetuses and then in the same animals 1 and 4 h after cesarean section delivery. Comparing fetal and 1-h lambs 1) systemic output fell by 33% (P < 0.005); 2) systemic plasma NE increased by 144% (P < 0.005), and plasma Epi increased sevenfold (P < 0.005); 3) total body NE spillover rose by 63% (P < 0.01) and Epi spillover by fivefold (P < 0.005); and 4) total body NE clearance decreased by 34% (P < 0.005) and Epi clearance by 37% (P < 0.005). Systemic blood flow and kinetic data were similar in 1- and 4-h lambs and were therefore pooled to define the interrelationship among perinatal changes in NE and Epi plasma levels, spillover, and clearance. Between fetal and newborn lambs, plasma NE rose by 1,375 +/- 207 pg/ml, of which 604 +/- 119 pg/ml (approximately 44%) resulted from increased NE total body spillover and 771 +/- 160 pg/ml from reduced NE total body clearance. In the same interval, plasma Epi rose by 292 +/- 30 pg/ml, of which 123 +/- 18 pg/ml (approximately 42%) was due to Epi total body spillover and 169 +/- 19 pg/ml to reduced Epi total body clearance. These findings indicate that 1) sympathoadrenal activity increases with birth, and 2) increased total body spillover and reduced total body clearance contribute a similar portion of the plasma NE and Epi surge at birth.
Animals↗
Cerebral metabolism and its relationship with sympathetic nervous activity in essential hypertension: evaluation of the Dickinson hypothesis.
OBJECTIVE: To examine Dickinson's hypothesis in mild essential hypertension, in which neurogenic mechanisms are believed to be particularly relevant, by combining measures of cerebral oxygen consumption with the concurrent assessment of sympathetic nervous activity. DESIGN AND METHODS: Twenty-five untreated essential hypertensive subjects and 28 healthy age-matched volunteers underwent direct blood sampling using percutaneously inserted catheters advanced into the internal jugular vein, with cerebral blood flow scans to differentiate between cortical and subcortical venous drainage of the brain. Venoarterial blood gas measurements and internal jugular vein blood flows were used to calculate cerebral respiratory quotients and cerebral oxygen utilization. The total body rate of noradrenaline spillover into plasma was measured to assess relationships between cerebral oxidative metabolism and sympathetic nervous activity. RESULTS: Compared with controls, the hypertensive subjects exhibited reductions in internal jugular vein blood flow (482 +/- 29 versus 410 +/- 15 ml/min), cerebral oxygen consumption (27 +/- 2 versus 23 +/- 1 ml/min) and cerebral oxygen supply (93 +/- 6 versus 78 +/- 3 ml/min). The cerebral respiratory quotients were identical (1.00 +/- 0.04 in normotensives and 0.98 +/- 0.03 in hypertensives). Technetium blood flow scans revealed that the reductions in internal jugular blood flow and cerebral oxygen consumption in the hypertensive patients were confined to cortical brain regions. Cortical blood flow was quantitatively linked to the matching respiratory quotient and oxygen consumption, neither of which bore any relation to the level of sympathetic nervous activity. The spillover of noradrenaline into the plasma for the body as a whole did not differ between the two groups. CONCLUSIONS: In accord with Dickinson's hypothesis, we have established a reduction in internal jugular vein blood flow and cerebral oxygen utilization in hypertension. These reductions were confined to cortical brain regions. However, cerebral respiratory quotients in our hypertensive study group were no different from those in our controls, suggesting that glucose remained as the major cerebral metabolic substrate in hypertension. We were not able to establish a link between cerebral metabolism and blood pressure or sympathetic nervous activity in mildly hypertensive patients.
Adult↗