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Biomedical subjects

G C Inglis

Publications and source records attributed to G C Inglis.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

Animals↗
PubMed1992

Dexamethasone-induced differentiation of atrial myocytes in culture.

Atrial and ventricular myocytes from fetal and newborn rats were cultured in medium supplemented with fetal or newborn calf serum with and without glucocorticoid. Myocyte morphology was examined by light and electron microscopy, and the amount of stored and secreted atrial natriuretic peptide (ANP) was measured. Without dexamethasone, neonatal atrial myocytes cultured for 7 days contained myofibrils organized into sarcomeres and numerous endocrine granules containing immunostainable ANP. Secretion of immunoreactive ANP reached a peak between days 7 and 9 of culture. Myocytes from fetal rats secreted ANP but contained few endocrine granules, and myofilaments were poorly organized. By contrast, the addition of dexamethasone (1 nM-1 microM) to the culture medium of newborn myocytes promoted development of numerous endocrine storage granules, mitochondria, and myofibrils with prominent Z-bands. Dexamethasone also increased the cellular content of ANP and ANP-specific mRNA in both atrial and ventricular myocytes. In the presence of dexamethasone myocytes maintained their structural integrity for periods of at least 45 days.

Animals↗
PubMed1992

Effects of long-term infusions of dopa and carbidopa on renin and steroid secretion in the rat.

Plasma, kidney, and adrenal catecholamine concentrations were varied by infusing rats with L-dopa and/or carbidopa for 2 weeks. L-Dopa infusion (300 micrograms/day) increased dopamine concentrations in plasma, adrenal zona glomerulosa, and kidney by 140%, 74%, and 224%, respectively: the dopamine content of the adrenal inner cortex plus medulla was not increased. Infusion of carbidopa alone had no detectable effect upon endogenous dopamine concentrations. Concomitant infusion (300 micrograms/day) of carbidopa with L-dopa blocked the rise in plasma and adrenocortical dopamine caused by L-dopa alone. Plasma aldosterone and plasma and kidney active renin concentrations were unaffected by L-dopa administration but plasma corticosterone and deoxycorticosterone (DOC) were significantly elevated (P < 0.05); increases in DOC appeared greater than those of corticosterone. These data cast doubt on the theory that dopamine is a physiological tonic inhibitor of aldosterone synthesis in rats. However, in the rat, stimulatory effects of L-dopa on plasma concentrations of precursors of aldosterone might be of physiological significance since DOC is a potent mineralocorticoid.

Adrenal Cortex↗
PubMed1990

Renin production by nephroblastoma cells in culture.

Nephroblastoma cells have been cultured for 19 days. During this time cell growth and active and inactive renin secretion were monitored. Inactive renin was found to be secreted in excess of active renin. The main secretory protein, precipitated with antirenin IgG was found to have a molecular mass of 52,000 daltons.

Cell Division↗
PubMed1988

Overnight clonidine suppression test in the diagnosis and exclusion of pheochromocytoma.

In a prospective study designed to differentiate pheochromocytoma from other forms of hypertension, urinary catecholamines were measured after sleep and clonidine administration in 12 patients with pheochromocytoma, 19 hypertensive patients in whom pheochromocytoma was suspected but later excluded, and 31 hypertensive patients in whom pheochromocytoma was never suspected. The test correctly identified all 12 patients in whom pheochromocytoma was present. Four of these had equivocal plasma levels of both norepinephrine and epinephrine, suggesting that overnight clonidine suppression may be of particular value when tumor secretion is intermittent or low. When pheochromocytoma was not present, urinary norepinephrine and epinephrine levels were suppressed below 60 and 20 nmol/mmol creatinine, respectively, after sleep and clonidine, the two in combination giving better suppression than sleep alone. Since urinary catecholamines can be determined relatively easily by high-pressure liquid chromatography with electrochemical detection, this test may be more widely applicable than suppression tests based on plasma measurements.

Adrenal Gland Neoplasms↗
PubMed1988

Circulating adrenaline and noradrenaline concentrations during exercise in patients with exercise induced asthma and normal subjects.

A failure of the usual increase in plasma adrenaline and noradrenaline concentrations during submaximal exercise has been suggested as a contributory cause of exercise induced asthma. Six normal subjects and six asthmatic patients underwent a standard graded maximal exercise test. Measurements of oxygen consumption, minute ventilation, exercise time, blood lactate concentration, and heart rate indicated that the two groups achieved similarly high work loads during exercise. Mean FEV1 fell by 20% in asthmatic patients after exercise. Basal plasma adrenaline concentrations (nmol/l) increased in normal subjects from 0.05 to 2.7 and in asthmatic patients from 0.12 to 1.6 at peak exercise. Noradrenaline concentrations (nmol/l) increased in normal subjects from 2.0 to 14.3 and in asthmatic patients from 1.9 to 13.7 at peak exercise. The increases in adrenaline and noradrenaline in the asthmatic patients did not differ significantly from the increases in normal subjects. Thus a reduced sympathoadrenal response to exercise seems unlikely to be an important mechanism in the pathogenesis of exercise induced asthma.

Adolescent↗
PubMed1987

The effects of insulin-induced hypoglycaemia on cardiovascular function in normal man: studies using radionuclide ventriculography.

The cardiovascular effects of an intravenous injection of soluble insulin and of acute hypoglycaemia were examined in six normal male subjects using multiple-gated radionuclide ventriculography. The basal left ventricular ejection fraction rose significantly from 47 +/- 3% (mean +/- SEM) to 54 +/- 3% p less than 0.01, within 5 min of the intravenous injection of insulin, and before any significant changes occurred in the blood glucose concentration. The ejection fraction subsequently rose to a peak of 72 +/- 5% coinciding with the onset of the acute hypoglycaemic reaction. This corresponded to the nadir of blood glucose and was associated with rises in heart rate, stroke volume and cardiac output. The heart rate returned to the resting value within 30 min of the acute hypoglycaemic reaction, but the ejection fraction, stroke volume and cardiac output were still elevated 90 min later. The peak ejection fraction value immediately preceded the maximal increment of plasma catecholamines released in response to hypoglycaemia. Thus, administration of intravenous insulin had a small, immediate, discernible effect on the cardiovascular system. A subsequent rise in left ventricular ejection fraction of much greater magnitude was stimulated by the development of acute hypoglycaemia, and was associated temporally with sympatho-adrenal activation. The use of radionuclide ventriculography showed that the haemodynamic changes provoked by hypoglycaemia produced a sustained effect on cardiac contractility.

Acute Disease↗
PubMed1987

Does dopamine regulate aldosterone secretion in the rat?

This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH). Adrenal concentrations (means +/- SE) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 +/- 335, 527 +/- 75 and 51 +/- 12 nmol/g in the medulla, and 66 +/- 17, 18 +/- 9 and 6 +/- 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were greater than 3030.4, 339.8 +/- 41.5 and 55.2 +/- 11.0 pmol/l in rats fed low, normal and high sodium diets respectively. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1987

Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes.

1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink. 2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol. 3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels. 4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink. 5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol. 6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin-angiotensin systems after alcohol.

Adolescent↗
PubMed1987

Neuropeptide Y in multiple endocrine neoplasia: release during surgery for phaeochromocytoma.

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.

Adrenal Gland Neoplasms↗
PubMed1986

Effect of low dose adrenaline and noradrenaline infusions on airway calibre in asthmatic patients.

Airway, cardiovascular and metabolic responses were measured in six asthmatic patients with stable asthma during separate adrenaline, noradrenaline and control infusions. Four incremental infusion rates (4, 10, 25 and 62.5 ng min-1 kg-1) produced circulating catecholamine concentrations within the physiological range. Specific airways conductance and maximal expiratory flow rates measured from complete and partial flow-volume curves increased significantly (P less than 0.05) during adrenaline infusion, in a dose-response manner. No changes in specific airways conductance or maximal expiratory flow rates were seen during the noradrenaline or control infusion. The highest adrenaline infusion rate caused a rise in systolic blood pressure (P less than 0.05) and plasma glucose (P less than 0.05) and a fall in plasma potassium (P less than 0.05). Noradrenaline infusion caused a slight increase in diastolic blood pressure (P less than 0.05) but no metabolic changes. No cardiovascular or metabolic changes occurred during the control infusion. Infused adrenaline, producing circulating concentrations within the physiological range, caused dose-related bronchodilatation in asthmatic patients. Circulating noradrenaline does not appear to have a role in the control of basal airway tone in asthmatic patients.

Adolescent↗
PubMed1985

The role of plasma osmolality, angiotensin II and dopamine in vasopressin release in man.

A sensitive and specific radioimmunoassay for arginine vasopressin was used to compare the relative importance of changes in plasma osmolality, angiotensin II and dopamine in the regulation of vasopressin secretion in man. One hour after water loading plasma vasopressin fell from 0.40 to 0.06 pmol/l, while 8 h and 24 h fluid restriction resulted in a rise of vasopressin from 0.29 to 0.54 and 1.37 pmol/l respectively. In contrast neither dietary sodium deprivation, when plasma angiotensin II increased 5-fold, nor dopamine infusion, at a rate which increased circulating dopamine levels up to 244-fold, had any effect on basal plasma vasopressin values. These results confirm that, under physiological conditions, osmoregulation is the major mechanism controlling vasopressin release and suggests that circulating angiotensin II and dopamine have no significant part to play.

Adult↗
PubMed1985

Airway responses to low concentrations of adrenaline and noradrenaline in normal subjects.

Airway, cardiovascular and metabolic responses were measured in six normal subjects during separate infusions of adrenaline and noradrenaline. Four incremental infusion rates of the catecholamines (4, 10, 25 and 62.5 ng X kg-1 X min-1) produced circulating levels of adrenaline and noradrenaline within the physiological range. Maximal expiratory flow rates at 25% of vital capacity measured from partial flow-volume curves increased sequentially with increasing adrenaline concentration. Increases in maximal expiratory flow rates at 25% and 50% of vital capacity measured from complete flow-volume curves were not statistically significant, nor were the changes in specific conductance. Small but insignificant changes were observed in heart rate and blood pressure during adrenaline infusion. Plasma glucose increased and serum potassium fell during adrenaline infusion. No significant airway, cardiovascular or metabolic responses were seen during noradrenaline infusion. These results suggest that adrenaline, at concentrations found in physiological circumstances, influences flow rates in small airways. Circulating noradrenaline does not appear to be important in the control of airway calibre in normal subjects.

Adult↗
PubMed1984

The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in normal female subjects.

The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in a group of seven healthy female subjects is reported. Subjects were infused with NaCl solution (154 mmol/l) (control) or dopamine (0.01 and 0.1 micrograms min-1 kg-1 for 120 min at each rate) on separate days in the early follicular phase of consecutive menstrual cycles. Serum prolactin decreased during infusion of dopamine at 0.01 micrograms min-1 kg-1 but a similar fall was found in the control group. When the rate of dopamine infusion was increased to 0.1 micrograms min-1 kg-1 a further substantial decrease in prolactin concentration occurred, whereas prolactin in the control group showed no change. At the end of the period of dopamine infusion at 0.1 micrograms min-1 kg-1 serum prolactin remained significantly (P less than 0.025) lower than in the control group (85 +/- 12 vs 180 +/- 21 m-units/1). No change in thyrotrophin (TSH), growth hormone (GH) or luteinizing hormone (LH) was seen during either rate of dopamine infusion compared with control. While dopamine infusion at 0.1 micrograms min-1 kg-1 caused significant inhibition of prolactin secretion in normal female subjects, other pituitary hormone secretion was not affected: it is suggested that under the conditions of this study dopamine in hypophysial portal blood is not of primary importance in the control of basal TSH, GH and LH release.

Adult↗
PubMed1984

Effect of the 5-hydroxytryptamine type 2 receptor antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympatho-adrenal function in patients with essential hypertension.

Ketanserin, a 5-HT type 2 receptor antagonist, was administered intravenously to nine patients with essential hypertension in a double-blind placebo controlled study to investigate the drug's effects on blood pressure, heart rate, the renin-angiotensin system and sympatho-adrenal function. Average blood-pressure for the group prior to injection of the drug was 150 +/- 7/94 +/- 4 (s.e. mean) mm Hg and decreased significantly (P less than 0.01) to 137 +/- 8/88 +/- 5 mm Hg during the 2 h after injection; heart rate increased immediately after injection of ketanserin, reaching a maximum of 81 +/- 4 beats/min. After drug administration systolic and diastolic blood pressure decreased on tilting, but the heart rate response was not different from that with placebo. Ketanserin did not affect the blood pressure response to graded infusion of the alpha 1-adrenoceptor agonist phenylephrine. Plasma active renin, angiotensin II and aldosterone concentrations increased slightly but not significantly after the drug; plasma noradrenaline increased transiently. 5-HT may be important in the maintenance of blood pressure but alternative mechanisms for the action of ketanserin in reducing blood pressure require investigation.

Adrenal Glands↗
PubMed1984

Pressor effects of brief and prolonged infusions of epinephrine in the conscious rat.

Plasma epinephrine may be increased in some patients with essential hypertension, and prolonged infusion of this catecholamine has been claimed to raise blood pressure. The objectives of our experiments were to determine whether continuous intravenous infusion of epinephrine raised blood pressure in a rat preparation known to respond in this way to angiotensin II in low dose and, if so, the plasma concentration of epinephrine required to raise pressure in comparison to the physiological range of plasma catecholamine concentration in the rat. Intravenous infusion of epinephrine at a rate of 400 ng X kg-1. min-1 or less for 30 min into Wistar rats did not increase mean arterial pressure (MAP); pressure did rise when the rate was increased to 800 ng X kg-1. min-1. However, when rats were given epinephrine at 400 ng X kg-1. min-1 for 4 days with continuous blood pressure recording, average MAP showed a progressive rise on successive days of infusion, reaching a maximum increase of 12 mmHg on the 4th and final day of infusion (P less than 0.02). Blood pressure did not change significantly during epinephrine infusion at 10 and 70 ng X kg-1. min-1. Plasma epinephrine was raised more than 13 times basal at the highest rate of infusion. In comparison, blood pressure and catecholamine concentrations increased only slightly although significantly during a period of restraint. We confirm the existence of a slowly developing pressor effect of epinephrine, but it is small and requires a large sustained increase of plasma epinephrine for its development.

Animals↗
PubMed1983

The effect of a 5-HT antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympathoadrenal function in normal man.

The role of endogenous 5-hydroxytryptamine (5-HT) in the control of blood pressure, the renin-angiotensin system and sympatho-adrenal function was investigated in normal man. Ketanserin (a specific 5-HT2 antagonist) administered intravenously caused a small decrease in blood pressure in salt-depleted recumbent subjects. A more marked postural fall in pressure occurred in both sodium-depleted and repleted normal subjects. Plasma active renin concentration and angiotensin II increased after administration of ketanserin, but plasma aldosterone, cortisol and noradrenaline were unchanged. 5-HT may be important in the control of blood pressure in man and specific 5-HT2 receptor antagonists could be a useful new class of antihypertensive agents.

Adrenal Glands↗