Bronchodilator effect of atrial natriuretic peptide in asthma.
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Adult↗
Biomedical subjects
J M Connell
Publications and source records attributed to J M Connell.
Effects of UK 69 578: a novel atriopeptidase inhibitor.
UK 69 578 is a competitive inhibitor of endopeptidase 24.11 (the enzyme that degrades atrial natriuretic factor) in vitro. In vivo, UK 69 578 has renal and cardiovascular effects similar to low-dose atrial natriuretic factor infusion, and may be a useful agent in hypertension and heart failure.
Animals↗
Harnessing the therapeutic potential of atrial natriuretic peptide.
The biological actions of Atrial Natriuretic Peptide (ANP) make it potentially useful in the treatment of hypertension and heart failure. We review here the physiology of ANP, the effects of infusion in heart failure and hypertension and preliminary data suggesting that inhibition of endopeptidase 24.11, the enzyme degrading ANP, is an effective mechanism of raising circulating levels of endogenous ANP. Due to the rate of progress in this field we have restricted ourselves to recent work much of which is still available only in abstract form. For more complete accounts the reader is referred to recent reviews [9, 11, 14].
Atrial Natriuretic Factor↗
Atrial natriuretic peptide in the fetus.
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Atrial Natriuretic Factor↗
The role of dopamine in the control of corticosteroid secretion and metabolism.
The relation between aldosterone and its trophins is altered by electrolyte status and in some hypertensive conditions in man by a mechanism or mechanisms not understood. Dopamine has been suggested as the agent for the altered sensitivity of plasma aldosterone to angiotensin II based on the results of studies with dopamine itself, both in vivo and in vitro, and with pharmacological agonists and antagonists. The evidence derived from these studies is presented and discussed. Questionable specificity of the agents used makes interpretation difficult. Similarly, dopamine infusion rates used in man and animals have resulted in plasma concentrations far in excess of those found normally and these pharmacological concentrations have been shown to alter both the clearance rate of exogenous angiotensin II, and the pattern of steroid response to ACTH. Direct study of adrenal tissue has provided more promising results. The adrenal cortex possesses specific dopamine receptors and dopamine has been shown to modify aldosterone biosynthesis in vitro. Moreover, dopamine is present in adrenocortical tissue in concentrations in the range calculated to operate the receptors. However, there is, as yet, no evidence that dopamine concentrations change in a physiological meaningful way, for example, during changes in sodium status.
Adrenal Cortex↗
Effect of infused dopamine on free fatty acids in normal females.
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Adult↗
The role of cortisol in the peripheral granulocyte response to insulin-induced hypoglycaemia in man.
Peripheral blood leukocyte counts and plasma hormonal changes in response to acute insulin-induced hypoglycaemia were examined in 16 patients undergoing assessment of pituitary function. Eight subjects had a normal cortisol secretory response (Group 1), and 8 patients had definite hypopituitarism in whom the cortisol responses were deficient or absent (Group 2). An equivalent degree of hypoglycaemia was achieved in both groups. In Group 1a biphasic rise in leukocyte count occurred following hypoglycaemia, with an early rise in lymphocytes at 15 minutes after the acute hypoglycaemic reaction, and a later rise in granulocytes. A similar rise in lymphocytes was observed in Group 2, but the rise in the granulocyte count was attenuated, increasing from a basal value of 3.6 +/- 0.6 x 10(9) cells/L to a peak of 7.4 +/- 1.1 x 10(9) cells/L, compared with a peak of 11.7 +/- 1.2 x 10(9) cells/L in Group 1 (P less than 0.05). The usual increment in plasma cortisol in response to hypoglycaemia occurred in Group 1, but plasma cortisol did not rise in Group 2. A correlation was observed between the magnitude of the granulocyte rise and the increment in plasma cortisol in individual subjects (r = 0.64, P less than 0.02). This suggests that the rise in peripheral granulocytes following insulin-induced hypoglycaemia in man is mediated by cortisol released from the adrenal gland, following activation of the hypothalamic-pituitary-adrenal axis.
Blood Glucose↗
Hydrallazine-induced Sjögren's syndrome.
4 years after initiation of therapy with hydrallazine hydrochloride (for treatment of hypertension), a 60-year-old male patient developed clinical features of Sjögren's syndrome, with immunological features of drug-induced systemic lupus erythematosus. In addition, the patient described rheumatoid arthritis-like symptoms and had reduced lacrimal and parotid salivary flow, but lacked the typical features of Sjögren's syndrome on labial gland biopsy. 1 year after discontinuation of hydrallazine therapy, the clinical parameters returned to normal.
Humans↗
Effects of indomethacin on steroid-induced changes in pressor responsiveness in man.
1. It has been shown previously that hydrocortisone (F) increases pressor responsiveness in normal subjects. The present study examined the role of vasodilator prostanoids in determining these changes. 2. Pressor responsiveness to angiotensin II (AII) (1-8 ng/kg per min) and phenylephrine (PE) (0.3-0.9 microgram/kg per min) was examined in six normal men receiving: no treatment (day 1); 100 mg indomethacin p.o. (INDO) in three divided doses over 20 h (day 2); 200 mg F for 5 days, 50 mg 6 hourly p.o. (day 6); F plus 100 mg INDO (day 7). 3. Blood pressure, body weight and plasma glucose rose with F and plasma potassium fell. F alone produced significant increases in response to AII at 2 ng/kg per min, for systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP), and at 1 ng/kg per min for DBP. The threshold for SBP, DBP and MAP rises with AII was decreased by F. Responses to PE following F were greater at 0.6 microgram/kg per min for SBP, DBP and MAP and the threshold for all parameters fell. 4. INDO alone had no significant blood pressure or metabolic effects and no effect on the magnitude of the blood pressure rise with AII, but decreased the threshold dose for effects on MAP. INDO had no effect on the magnitude of the pressure rise with PE, but decreased the threshold dose for effects on SBP. 5. INDO did not modify responsiveness or threshold to AII following F. Responsiveness to PE was unchanged and threshold fell for SBP only during INDO.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical response of thyrotropin-secreting macroadenoma to bromocriptine and radiotherapy.
A patient presenting with hyperthyroidism was treated initially with antithyroid drugs and subsequently radioiodine. Thereafter he was noted to have inappropriately elevated thyrotropin. A bitemporal visual field defect was noted and CT scan confirmed the presence of a pituitary tumour. TSH was elevated and unresponsive to TRH stimulation. alpha subunit was not elevated. Long-term bromocriptine therapy (doses up to 50 mg/day) resulted in partial, but incomplete suppression of thyrotropin secretion. Following radiotherapy there was resolution of the visual field defect; the TSH, however, remains elevated at greater than 20 mU/l. Radiotherapy and bromocriptine may provide a clinically useful alternative to pituitary surgery in patients with TSH-secreting macroadenoma with suprasellar extension.
Adenoma↗
Stimulation of cortisol production in isolated bovine zona fasciculata cells by phorbol ester: role of ion fluxes.
The role of protein kinase C activation in the control of cortisol synthesis was studied using the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA). Bovine zona fasciculata cells were incubated with various concentrations of TPA in the presence and absence of EGTA, verapamil or nitrendipine to see whether cortisol stimulation was dependent on extra-cellular calcium ions. When free extracellular concentration of Ca2+ was reduced to approximately 10 mumol/l the cortisol response at all concentrations of TPA was reduced by approximately 25% indicating that protein kinase C activation is only partially dependent on extracellular calcium ions. This is confirmed by the effects of the voltage-dependent calcium channel blocker verapamil, which partially inhibited the cortisol response to a maximally effective concentration of TPA (1 mumol/l). However, a second channel blocker, nitrendipine, proved to be ten times more potent than verapamil and totally inhibited the TPA response. The partial effects of EGTA and verapamil and the contrast between verapamil and nitrendipine do not exclude the possibility that intracellular calcium ions are important in protein kinase C activation and may indicate that nitrendipine has better access to an additional site of inhibitory action than verapamil. It is significant that the ionophore A23187, which facilitates Ca2+ entry independently of voltage-sensitive channels, failed to overcome the inhibitory effects of nitrendipine in TPA-stimulated cells. In some other tissues, the effects of protein kinase C activation are mediated by the opening of Na+/H+ exchange ports. The involvement of this port in the cortisol response has been tested by incubating TPA- and ACTH-treated cells with amiloride, an inhibitor of Na+/H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex↗
Haemodynamic, hormonal and renal effects of adrenocorticotrophic hormone in sodium-restricted man.
The effect of a dietary sodium restriction (15 mmol/day) on the development of adrenocorticotrophic hormone (ACTH) hypertension was examined in six normal male subjects. When ACTH (1 mg/day) was given for 5 days to subjects on a sodium-restricted diet, systolic blood pressure rose (116 +/- 4 to 125 +/- 4 mmHg, P less than 0.001), while diastolic blood pressure was unchanged. There was a modest antinatriuresis (cumulative Na+ balance, 59 +/- 2 mmol) which was reflected in a small rise in exchangeable body sodium (65 +/- 15 mmol); plasma concentrations of active renin and angiotensin II both fell during ACTH treatment. Plasma volume rose (2.8 +/- 0.2 to 3.6 +/- 0.16 l, P less than 0.01) while extracellular fluid volume was unchanged. Plasma concentration of atrial natriuretic peptide (ANP) rose to more than twice basal. Glomerular filtration rate (inulin clearance) increased (111 +/- 9 to 131 +/- 7 ml/min, P less than 0.001), renal plasma flow, measured as the rate of para-aminohippurate (PAH) clearance, was unaltered and calculated filtration fraction rose. Dietary sodium restriction did not, therefore, prevent an ACTH-induced increase in blood pressure. The increase in plasma volume with ACTH is not dependent on renal sodium retention and is associated with increased concentrations of ANP. When these data are compared with findings previously reported in subjects given the same dose of ACTH when on normal or high sodium intakes, it is clear that, although the action of ACTH in raising blood pressure is not dependent on exogenous sodium or extracellular fluid volume expansion, sodium retention can modify the level of blood pressure attained.
Adrenocorticotropic Hormone↗
Imaging with pentavalent [99mTc]DMSA in patients with medullary cancer of the thyroid.
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Adult↗
Chronic low-dose infusions of dexamethasone in rats: effects on blood pressure, body weight and plasma atrial natriuretic peptide.
Glucocorticoid-induced hypertension in rats has been studied using long-term, low-dose dexamethasone treatment. Dose-related increases in systolic blood pressure were achieved, without loss in body weight, with subcutaneous continuous infusions of 1, 2 and 5 micrograms dexamethasone per day, respectively, for 4 weeks. Rats treated with 10 micrograms dexamethasone per day lost weight at a rate of 10 g per week. Lower doses caused a significant reduction in weight gain compared with controls. Renin, aldosterone, plasma sodium and potassium concentrations were unaffected by dexamethasone treatment. Plasma atrial natriuretic peptide (ANP) concentrations were decreased by 40-50% by dexamethasone. These decreases were negatively correlated with increases in systolic blood pressure and haematocrit. Glucocorticoid-induced decreases in ANP contrast with ANP increases in response to mineralocorticoid treatment in rats with deoxycorticosterone-induced hypertension. Plasma concentrations of the endogenous glucocorticoid, corticosterone, were suppressed to the same very low levels by 5 and 10 micrograms dexamethasone per day; 1 and 2 micrograms doses were less effective. Unlike mineralocorticoid-induced hypertension, the pressor effects of dexamethasone were ameliorated but not abolished by dietary sodium restriction and were unaffected by sodium loading. Two micrograms of dexamethasone reduced plasma ANP in rats on either high- or low-sodium diets by 29 and 34%, respectively. We conclude that low-dose infusions (less than 5 micrograms/day) of dexamethasone are suitable for studying glucocorticoid-induced hypertension without the complications of weight loss that have been reported by others or of the mineralocorticoid-like side effects which endogenous glucocorticoids may exhibit.
Animals↗
Growth hormone, body composition and somatomedin C after treatment of acromegaly.
Acromegaly is associated with abnormal indices of body composition (as determined by exchangeable sodium, exchangeable potassium and total body water estimations) which may be corrected by treatment. We related these indices of body composition to the attained growth hormone levels (mean of five daytime values) in 42 treated acromegalics. Somatomedin C was measured in 30 subjects. The mean duration of treatment was 7.7 years (range 1-26). Exchangeable sodium, potassium and total body water were significantly lowered by treatment. After treatment of acromegaly subjects whose growth hormone level was below 5 mU/l achieved normal body composition more often than those with higher levels. Growth hormone concentration of below 5 mU/l after treatment should be regarded as more appropriate index of control of acromegaly than the higher levels previously recommended.
Acromegaly↗
Radioprotective action of carbimazole in radioiodine therapy for thyrotoxicosis--influence of the drug on iodine kinetics.
Pretreatment with carbimazole of patients given radioiodine (131I) therapy for thyrotoxicosis reduces the incidence of early hypothyroidism. The possibility that this radioprotective effect might be a consequence of drug induced alteration in thyroidal iodide turnover, leading to a reduction in thyroid irradiation, was investigated in a prospective study of 24 thyrotoxic patients. Subjects were randomly assigned to receive 131I alone or to be treated with carbimazole for a minimum of three months before 131I. Thyroxine supplements were given in the latter group to prevent iatrogenic hypothyroidism. The effective half-life of therapeutic 131I in the thyroid was measured using a gamma camera/computer system after oral administration of the dose, allowing the biological half life of the anion and estimated radiation dose to the thyroid to be derived. Effective half life of 131I, biological half life of 131I and estimated radiation dose to the thyroid were similar in the two groups of subjects. It is concluded that the radioprotective action of carbimazole is not a consequence of altered thyroidal iodide kinetics.
Carbimazole↗
Circadian variation of thyrotrophin, determined by ultrasensitive immunoradiometric assay, and the effect of low dose nocturnal dopamine infusion.
The effect of low dose dopamine infusion on the circadian rhythm of thyrotrophin (TSH), prolactin and cortisol in a group of six healthy male volunteers is reported. Subjects were infused in random order with either saline (154 mmol/l NaCl solution; control) or dopamine (0.1 and 1 microgram min-1 kg-1) between 21.00 and 01.00 hours, in random order. The serum TSH profile was characterized by a maximal peak occurring at 23.00 hours and higher nocturnal than diurnal values. Superimposed on this are short term oscillations in serum TSH levels, typical of an ultradian rhythm. The maximal peak in TSH, occurring at 23.00 hours, was abolished by dopamine infused at a rate of 1 microgram min-1 kg-1, and was unaffected by the lower rate of dopamine infusion (0.1 microgram min-1 kg-1). The serum prolactin profile was characterized by a peak occurring soon after the onset of sleep (23.30-00.30 hours), which fell during the morning, and began to rise in late evening. Low dose dopamine (0.1 microgram min-1 kg-1) had a slight but insignificant effect with decreased prolactin levels at the end of the infusion whereas the higher dopamine dose was associated with significantly lower prolactin levels during and throughout the infusion. There was a rebound to levels significantly higher than control on cessation of the infusion. Cortisol levels were unaffected by dopamine.
Adult↗