The effects of alcohol on local, neural and humoral cardiovascular regulation.
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Acetaldehyde↗
Biomedical subjects
L G Howes
Publications and source records attributed to L G Howes.
An improved approach for the determination of plasma [3H]noradrenaline kinetics using high-performance liquid chromatography.
An improved approach for the determination of plasma [3H]noradrenaline ([3H]NA) kinetics in man is described, incorporating the extraction of plasma [3H]catechols on alumina and separation of [3H]NA from [3H]dihydroxymetabolites by high-performance liquid chromatography (HPLC). After a 30 min intravenous infusion, [3H]NA accounted for 57.2 +/- 13.2% of the radioactivity recovered by the procedure, while the dihydroxy-metabolites 3,4-[3H]dihydroxyphenylethylene. glycol ([3H]DHPG) and 3,4-[3H]dihydroxymandelic acid ([3H]DOMA) accounted for 32.3 +/- 11.5% and 4.9 +/- 6.0% respectively. After 90 min of constant infusion the proportion due to [3H]NA fell to 44.4 +/- 10.4%, while that due to [3H]DHPG rose to 45.9 +/- 9.5% because of an increase in the amount of [3H]DHPG at the later time. Plasma [3H]NA radioactivity rose rapidly during the constant infusion and usually reached a plateau by 30 min. However, in individual subjects large variations in plasma [3H]NA radioactivity occurred during the course of the infusion, implying rapid and variable changes in plasma [3H]NA clearance. The inclusion of a step to separate [3H]NA from [3H]dihydroxymetabolites is necessary if the aim is to determine plasma [3H]NA kinetics, as a large proportion of the radioactivity recovered from plasma on alumina is due to the presence of these metabolites.
Adult↗
Changes in blood pressure and autonomic reflexes following regular, moderate alcohol consumption.
Blood pressure, heart rate and responses to a range of autonomic reflex tests were studied in 10 normotensive male volunteers following 7 days of regular alcohol consumption (0.8 g/kg per day) or 7 days of abstaining from alcohol in a crossed, random order, open study. Systolic and diastolic pressures were significantly higher following alcohol intake than the alcohol-free control period (mean rise of 3.0 mmHg systolic and 3.1 mmHg diastolic, P less than 0.05 and P less than 0.01, respectively). Regular alcohol consumption attenuated the rise in blood pressure during isometric exercise and hand immersion in ice water, but did not affect blood pressure or heart rate responses to bicycle exercise. Resting, supine plasma noradrenaline levels, increases in noradrenaline levels during sympathetic activation and vagal reflexes (standing to lying test, diving reflex and Valsalva manoeuvre) did not differ significantly between the alcohol and control phases of the study. These findings support previous evidence that regular alcohol consumption decreases adrenoceptor mediated cardiovascular reactivity. However, the relationship between this effect and the rise in blood pressure that follows regular, moderate alcohol consumption remains unclear.
Adolescent↗
Plasma [3H]-noradrenaline kinetics and blood pressure following regular, moderate ethanol consumption.
Normotensive male volunteers (n = 8) either abstained from ethanol for 4 days or consumed 66 g of ethanol per day in an open, crossed, random order study. Mean arterial pressures rose by an average of 5.4 mmHg following the ethanol phase of the study (P less than 0.001). Plasma noradrenaline (NA) concentration was higher during ethanol ingestion (P less than 0.01), principally because of a significant reduction in NA clearance of -1.51 l min-1 m-2 (P less than 0.05). In contrast, NA spillover or release rates did not significantly differ between the two study periods. Total plasma calcium levels were significantly lower (P less than 0.05) following the ethanol compared to the control period. These data do not appear to support the proposition that regular alcohol consumption raises blood pressure by producing a generalised increase in sympathetic activity.
Adult↗
Comparison of plasma 3,4-dihydroxyphenylethylene glycol (DHPG) and norepinephrine levels as indices of sympathetic activity in man.
Plasma levels of norepinephrine (NE) and the NE metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) were measured simultaneously following sympathetic activation induced by standing, cold pressor testing and bicycle exercise at progressively increasing workloads in normal volunteers. Free DHPG and NE levels both increased with sympathetic activation, but free NE levels were a more sensitive index of change. In addition, plasma free NE levels more closely reflected the fall in heart rate following exercise than free DHPG. In contrast to free levels, conjugated DHPG and NE levels did not change significantly after exercise. Supine resting free DHPG/NE ratios were always greater than 2.0, but fell progressively with increasing sympathetic activation because of a proportionately greater rise in NE than DHPG. The simultaneous measurement of plasma free DHPG and NE does not offer advantages over free NE levels as an index of sympathetic activity in man, but may be of use in the diagnosis of pheochromocytoma and in studies of NE metabolism.
Adrenal Gland Neoplasms↗
The influence of age and sex on cardiac, renal and caudal artery catecholamine content in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats.
Noradrenaline (NA), adrenaline (A) and dopamine (DA) levels were measured in the heart, kidney and caudal artery of male and female SHR and WKY rats aged 6, 14 and 28 weeks, and the influence of strain, sex and age on catecholamine content determined. Levels of A were elevated in all three regions of SHR compared to WKY rats, independent of age and sex. This may represent increased A accumulation in sympathetic nerves resulting from the increased sympatho-adrenomedullary hyper-reactivity of the SHR strain. DA levels were also elevated in the heart and kidney of SHR rats, independent of sex and age. Na levels were lower in the heart of SHR rats, but this appeared to be partly a consequence of cardiac hypertrophy and partly due to strain difference between older male but not female rats. Thus a simple association between decreased cardiac NA levels and hypertension appeared unlikely. It is emphasised that further genetic studies of F2 backcross rats would be required to establish an etiological association between these differences in catecholamine levels and differences in blood pressure between the SHR and WKY strains.
Age Factors↗
Changes in brainstem and spinal adrenoceptor binding with ageing in spontaneously hypertensive and Wistar-Kyoto rats.
Adrenoceptor binding in membranes prepared from the brainstem and thoracic spinal cord of male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats aged 6 and 36-40 weeks has been compared. Binding of [3H]prazosin (alpha 1-receptors), [3H]rauwolscine (alpha 2-receptors) and [3H]dihydroalprenolol (DHA: beta-receptors) fell with age in both regions in both strains. Strain, independent of age, was also a significant determinant of binding for all three ligands in brainstem and for [3H]DHA in spinal cord. The changes in receptor binding may reflect differences in noradrenergic activity with age and between SHR and WKY rats.
Aging↗
Simultaneous assay of 3,4-dihydroxyphenylethylene glycol and norepinephrine in human plasma by high-performance liquid chromatography with electrochemical detection.
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Animals↗
Changes in plasma free 3,4-dihydroxyphenylethylene glycol and noradrenaline levels after acute alcohol administration.
The effects of alcohol (0.9 g/kg) compared with placebo (400 ml of orange juice) on plasma noradrenaline and 3,4-dihydroxyphenylethylene glycol levels, and on erect and supine blood pressures and heart rates, were studied in eight normal male volunteers. Alcohol caused a rise in noradrenaline levels that commenced approximately 30 min after drinking and lasted about 4 h. In contrast, 3,4-dihydroxyphenylethylene glycol levels fell immediately after alcohol administration and remained low for at least 6 h. Acute alcohol administration alters noradrenaline catabolism, and may have a dual effect of increasing noradrenaline release and decreasing noradrenaline clearance. Alcohol caused a transient rise in erect and supine blood pressures that preceded the rise in plasma noradrenaline. Thereafter erect blood pressures fell compared with control. This fall was associated with a progressive rise in both supine and erect rates, and reached a maximum several hours after the maximum levels of blood alcohol. The major effect of acute alcohol administration is to lower blood pressure and induce a reflex tachycardia. Changes in noradrenaline and 3,4-dihydroxyphenylethylene glycol levels did not readily explain changes in blood pressure or heart rate, suggesting that alcohol induced changes in noradrenaline metabolism occur largely independent of changes in blood pressure and heart rate.
Adult↗
The measurement of central noradrenergic activity in spontaneously hypertensive rats: a comparison of free 3,4-dihydroxyphenylethyleneglycol levels with FLA-63 induced noradrenaline depletion.
Noradrenergic activity was measured in the brainstem, hypothalamus and thoracic spinal cord of male and female spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 6 and 28-36 weeks of age. Two techniques were used, measurement of a major noradrenaline (NA) metabolite, free 3,4-dihydroxyphenylethyleneglycol (DHPG), and measurement of the rate of decline in brain NA levels following dopamine-beta-hydroxylase (DBH) inhibition by FLA-63. There was a good correlation between the changes with age in NA turnover measured by the two techniques. NA levels and NA turnover measured by both techniques fell with age in brainstem and thoracic spinal cord in both SHR and WKY rats. In both strains these falls in turnover were associated with increases in blood pressure. However, the increase in blood pressure in the SHR was greater than in the WKY, even though NA turnover fell to a similar extent in both strains. These data show a difference in the pattern of change in NA levels and turnover in the brainstem and thoracic spinal cord compared to other brain regions and may therefore be related to the development of higher levels of blood pressure in older rats in both strains. They do not offer a simple explanation for the much higher blood pressures seen at all ages in the SHR.
Animals↗
Decreased vascular responsiveness to noradrenaline following regular ethanol consumption.
Ten normal volunteers consumed 80 g of ethanol per day or abstained from ethanol for 4 consecutive days prior to measurements of blood pressure, heart rate, vascular responsiveness to noradrenaline (NA) and angiotensin II (AII) infusions and sympathetic responsiveness to isometric handgrip exercise in an open, random order, crossed study. Supine systolic and diastolic pressures and heart rates, and erect systolic pressures rose significantly following ethanol. Vascular responsiveness to NA infusions was reduced in all subjects following ethanol, while responses to AII infusions did not show a consistent pattern of change. Plasma renin activity, plasma NA and adrenaline concentrations, and concentrations of the NA metabolite 3,4 dihydroxyphenylethylene glycol (DHPG) did not significantly differ following ethanol and control treatments. The rise in plasma NA following 2 min isometric handgrip at 50% of maximal effort was greater following ethanol (0.24 +/- 0.21 nM) than control (0.12 +/- 0.10 nM) but the difference did not reach statistical significance. The pressor effect of regular ethanol consumption and the reduced vascular reactivity to NA may both be the result of an increase in sympathetic activity that was not large enough to measurably alter resting plasma NA concentrations.
Adult↗
Changes in blood pressure and vascular reactivity in normotensives following regular alcohol consumption.
Blood pressure and vascular reactivity to infusions of noradrenaline and angiotensin II (ANG II) were measured in 10 normotensive volunteers who had consumed 80 g alcohol per day for 4 days after a similar period of abstaining from alcohol. Supine systolic and diastolic blood pressure and heart rate, and erect systolic blood pressures rose significantly following alcohol. Vascular reactivity to noradrenaline decreased following alcohol, while reactivity to ANG II did not change in a consistent manner. Although plasma noradrenaline levels did not alter following alcohol, the decrease in vascular reactivity to noradrenaline may indicate down-regulation of alpha-receptors and provide indirect evidence that increased sympathetic activity contributes to the rise in blood pressure that follows regular, moderate alcohol consumption.
Adult↗
Assay of brain 3,4-dihydroxyphenylethyleneglycol (DHPG) levels by high-performance liquid chromatography with electrochemical detection. Factors affecting stability during sample preparation.
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Animals↗
Central catecholaminergic neurones and spontaneously hypertensive rats.
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Animals↗
Age related changes of catecholamines and their metabolites in central nervous system regions of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats.
Adrenaline (A), dopamine (DA), noradrenaline (NA) the NA metabolite 3,4-dihydroxyphenylethylene-glycol (DHPG) and the DA metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) were assayed in brain regions of male and female WKY and SHR at 6, 14, 28 and 36-40 weeks. Age related differences in catecholamine levels between the two strains were only seen with NA measurements. DOPAC levels were elevated in the striatum of SHR compared to WKY rats at all ages studied which might reflect the known hyperactivity of SHR strain. In the SHR NA but not DHPG levels in several regions, DA and DOPAC levels in midbrain and DA levels in lower brainstem were elevated at 6 weeks of age. These changes may represent a generalized alteration in central catecholamine metabolism in SHR during the early development of hypertension or merely reflect strain differences. It is emphasised that further genetic studies of F2 backcross rats are required to establish an aetiological association between these differences in catechol levels and differences in blood pressure between SHR and WKY rats.
3,4-Dihydroxyphenylacetic Acid↗
The simultaneous determination of 3,4-dihydroxyphenyl-ethylene glycol, 3,4-dihydroxyphenylacetic acid and catecholamines in brain tissue by high performance liquid chromatography with electrochemical detection.
An assay is described for the simultaneous determination of the deaminated metabolites 3,4-dihydroxyphenylethylene glycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC), together with noradrenaline, dopamine and adrenaline in brain using high performance liquid chromatography with electrochemical detection. The procedure is simple, specific, and has a limit of detection for each catechol of 5 pg. It offers the advantage of measuring the major monoamine oxidase metabolites of both noradrenaline (i.e. DHPG) and dopamine (i.e. DOPAC), which in some circumstances may reflect neuronal activity, simultaneously with their catecholamine neurotransmitter precursors.
3,4-Dihydroxyphenylacetic Acid↗
Antihypertensive effect of diltiazem in young or adult rats of genetically hypertensive strains.
The antihypertensive effects of diltiazem were investigated in three different strains of genetically hypertensive rats, i.e. spontaneously hypertensive rats (SHR), stroke prone SHR (SHR-sp) and genetically hypertensive rats (GHR) compared to their respective controls, normotensive Wistar-Kyoto (NT-WKY) and New Zealand strain (NT-NZ). Either adult (3-6 months) or young (4 weeks), conscious rats were used. In adult SHR, SHR-sp and GHR, the percent decrease in blood pressure produced by diltiazem (10, 30 and 100 mg/kg orally (p.o.) or 0.1, 0.3, 1.0 and 3.0 mg/kg intravenously (i.v.)) was greater than in NT-WKY or NT-NZ, while no difference was detected in case of hydralazine (5 mg/kg p.o.). In contrast, the reactivity to diltiazem was not different between the young rats bred from the normotensive and hypertensive rats of both the Japanese and the New Zealand strains. It is concluded that diltiazem is a more effective antihypertensive agent in the hypertensive rats than in the normotensive rats. However, the increased reactivity to this compound in the adult hypertensive rats cannot be readily explained by the known pathogenetic factors leading to their hypertension.
Age Factors↗