Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 181 records · Page 10Linked to original sources

PubMed1987

Chronic treatment of the spontaneously hypertensive rat with captopril attenuates responses to noradrenaline in vivo but not in vitro.

We have studied the attenuation by captopril of sympathetic neurotransmission in spontaneously hypertensive rats. Captopril (4 mg/kg for 15-17 days or 20 mg/kg for 4 days) was delivered i.v. by osmotic minipump. The higher dose lowered blood pressure, the lower dose did not. Both doses inhibited converting enzyme activity. In the pithed rat, both doses attenuated responses to exogenous noradrenaline and sympathetic nerve stimulation. In isolated tail arteries removed from captopril-treated rats, responses to sympathetic nerve stimulation and exogenous noradrenaline were the same as in controls. Perfusion of the tail artery of control rats with captopril, angiotensin I or angiotensin II had no effect on basal perfusion pressure or on vasoconstriction induced by exogenous noradrenaline or sympathetic nerve stimulation. Our results are consistent with the hypothesis that: 1. the attenuation of sympathetic neurotransmission by captopril depends upon the presence of an intact renin-angiotensin system, and 2. captopril has no direct postsynaptic effect in the isolated tail artery preparation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

Effect of prolonged clonidine treatment and its withdrawal on noradrenaline turnover in the cerebral cortex and medulla oblongata of the spontaneously hypertensive rat.

We have investigated the effect of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.5 mg . kg-1 X 24 h-1 for 10 days) and of withdrawal of this treatment on ingestive behaviour and on the cerebral turnover of noradrenaline in the adult spontaneously hypertensive rat (SHR). Clonidine amplified the fall in food and water intakes induced by minipump implantation. Ingestive behaviour returned to normal by the 4th to the 5th day in controls and by the 7th to the 8th day in clonidine-treated SHR. Clonidine withdrawal produced an increase in water intake above pre-implantation values. Body weight fell during clonidine treatment, then recovered slightly during withdrawal. After 5 days' treatment total DOPEG levels (an index of noradrenaline turnover) were reduced in cerebral cortex and medulla oblongata. The noradrenaline metabolite levels increased following withdrawal of drug treatment, the increase being more marked and faster in onset in cerebral cortex than in medulla oblongata. Thus prolonged treatment with clonidine decreases noradrenaline turnover and withdrawal of such treatment increases turnover.

Animals↗

PubMed1987

Noradrenaline inhibits vasoconstriction induced by electrical stimulation.

Exposure of the isolated rat tail artery to exogenous noradrenaline inhibited vasoconstriction induced by electrical field stimulation. Phenylephrine produced brief inhibition; guanfacine potentiated electrical stimulation. Sympathetic neurotransmission may be blunted by brief increases in circulating noradrenaline levels.

Animals↗

PubMed1987

Scalp infections in black children: think kerion.

Treatment of tinea capitis consists of a 5-week course of griseofulvin. A 1-week course of a systemic corticosteroid may be considered in addition to griseofulvin therapy to accelerate the subsidence of inflammation in kerion lesions. Kerion is an inflammatory form of tinea capitis which may progress rapidly into a fulminant infection if untreated. This case report underscores the need for prompt recognition and appropriate treatment of this disorder.

Abscess↗

PubMed1987

Phosphorylation of purified rat striatal tyrosine hydroxylase by Ca2+/calmodulin-dependent protein kinase II: effect of an activator protein.

The phosphorylation of tyrosine hydroxylase, purified from rat striatum, was investigated using purified Ca2+/calmodulin (CaM)-dependent protein kinase II. This kinase catalyzed the Ca2+-dependent incorporation of up to 0.8 mol 32PO4/mol tyrosine hydroxylase subunit (62 kilodaltons). Reverse-phase high-performance liquid chromatography mapping of tryptic 32P-peptides established that the Ca2+/CaM-dependent protein kinase II phosphorylated a different serine residue than was phosphorylated by the cyclic AMP-dependent protein kinase. Limited proteolysis sequentially reduced the subunit Mr from 62 to 59 kilodaltons and finally to 57 kilodaltons, resulting in loss of the site phosphorylated by the Ca2+/CaM-dependent protein kinase II, but not the site phosphorylated by the cyclic AMP-dependent protein kinase. Phosphorylation by the Ca2+/CaM-dependent protein kinase II had little direct effect on the kinetic properties of tyrosine hydroxylase, but did convert it to a form that could be activated twofold by addition of an activator protein. This heat-labile activator protein increased the Vmax without affecting the Km for the pterin cofactor. This effect was specific in that the activator protein was without effect on nonphosphorylated tyrosine hydroxylase or on tyrosine hydroxylase phosphorylated by the cyclic AMP-dependent protein kinase. These results are consistent with the hypothesis that the "Vmax-type" activation of tyrosine hydroxylase observed upon depolarization of neural and adrenal tissues may be mediated by the Ca2+/CaM-dependent protein kinase II.

Animals↗

PubMed1987

Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline.

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks' unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.

Animals↗

PubMed1987

The role of the renin-angiotensin system in normotensive and hypertensive rats with varying renin status.

We have investigated the relationship between the acute blood pressure lowering effect of captopril and renin status. Differences in renin status were induced by unilateral artery clipping combined with unilateral or bilateral nephrectomy in rats. The blood pressure lowering effect of captopril correlated very closely with plasma or aortic renin across a very wide range of renin levels.

Anesthesia↗

PubMed1986

High-affinity binding sites for human Glu-plasminogen unveiled by limited plasmic degradation of human fibrin.

The binding of human 125I-Glu-plasminogen to human plasmin-degraded fibrin was studied. Treatment of preformed and polymerized fibrin with 0.01 IU plasmin/ml resulted in an increased binding of 125I-Glu-plasminogen depending upon the length of time of preincubation of fibrin with plasmin. Binding reached a plateau of 30% of total added radioactivity after 60 min. At this time, less than 10% of fibrin had been digested. Polyacrylamide/urea/acetic acid gel electrophoresis revealed that the radioiodinated plasminogen bound to plasmin-degraded fibrin was of the Glu form. Computerized non-linear regression analysis of the binding experiments revealed that limited plasmic degradation of fibrin progressively generates high-affinity binding sites (Kd approximately equal to 0.3 microM) for Glu-plasminogen. At the time of maximal Glu-plasminogen binding approximately 5 high-affinity binding sites per 100 molecules of fibrin had been generated. The low-affinity type of binding sites were also identified. These observations describe a new mechanism which exquisitely modulates the plasmic breakdown of fibrin by a continuous renewal of high-affinity binding sites for Glu-plasminogen on the surface of the fibrin gel during the fibrinolytic process.

Binding Sites↗

PubMed1986

Chronic clonidine treatment and its withdrawal: effects on blood pressure and catecholamine synthesizing enzymes in brain-stem nuclei.

We have studied the effects of withdrawal from chronic clonidine treatment in the adult male spontaneously hypertensive rat (SHR). SHR received clonidine, 0.1 mg X kg-1 X day-1 i.v. for 10 days. Clonidine was delivered via osmotic minipumps. After 7 days of treatment there was a 16.5 +/- 2.5 mm Hg fall in mean arterial pressure. This was accompanied by a decrease in the dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase activities of the A1/C1 region. Withdrawal from clonidine was characterized by tachycardia and an increase in mean arterial pressure and heart rate lability. Phenylethanolamine-N-methyl transferase of the the dopamine-beta-hydroxylase activity remained diminished. The dopamine-beta-hydroxylase activity of the A2/C2 region was also diminished during withdrawal. We suggest that the blood pressure lowering effect of clonidine is accompanied by a decreased capacity to synthesize adrenaline in the A1/C1 region where adrenaline could mediate a pressor effect. Increased blood pressure lability during withdrawal is accompanied by a restoration of synthesis of adrenaline in the A1/C1 region. There is also a decrease in the capacity of synthesis of noradrenaline in the A2/C2 region where adrenaline may mediate a vasodepressor effect.

Adrenal Medulla↗

PubMed1986

Sensitivity to noradrenaline and electrical stimulation decreases with age in the rat tail artery.

We have studied vasoconstrictor responses to noradrenaline and electrical field stimulation in the isolated perfused/superfused tail arteries of rats of 6-7, 16-17 and 30-31 months of age. Maximal vasoconstrictor responses to noradrenaline were the same at all three ages. Sensitivity to noradrenaline and to electrical stimulation were reduced in the 16-17 and 30-31 month old rats. The noradrenaline content of the arteries of the two latter age groups was reduced. We conclude that aging in this resistance vessel is accompanied by a decrease in the arterial noradrenaline content and in the sensitivity of the artery to noradrenaline.

Aging↗

PubMed1986

Discriminative properties of the psychostimulant dl-cathinone in a two lever operant task. Lack of evidence for dopaminergic mediation.

In order to analyse further the discriminative stimulus properties of stimulant drugs, rats were trained to discriminate 2.0 mg/kg of dl-cathinone in a two-lever operant task. Dose-related generalization was seen to cathinone itself and to a wide range of stimulant drugs including d-amphetamine, cocaine, methylphenidate, pipradrol and cathine, i.e. (+)norpseudoephedrine. The high degree of specificity of the cathinone cue at the specific training dose studied was shown by the fact that the following nonstimulant drugs failed to generalize at all to cathinone, even in large doses--haloperidol, chlordiazepoxide, fenfluramine and fentanyl. The cathinone cue at 2.0 mg/kg was probably of central origin because phydroxyamphetamine (a polar congener of amphetamine) failed to generalize to cathinone at a dose nearly 50 times the ED50 for amphetamine generalization. Phenylethylamine (PEA; alpha-demethylamphetamine) and deuterated phenylethylamine (alpha, alpha, d2-PEA), a long acting derivative of phenylethylamine which is resistant to metabolism by monoamine oxidase, produced at most partial (60%) generalization to cathinone, even in large doses. alpha-Demethylcathinone failed to generalize at all to cathinone at doses up to 10 times the ED50 for cathinone. Thus, the alpha-methyl groups of both amphetamine and cathinone are important in determining their cue properties. The involvement of dopaminergic systems in the cathinone cue was investigated by examining generalization to apomorphine and antagonism by haloperidol. Apomorphine produced at most 29% generalization to cathinone. Haloperidol, at doses up to 0.3 mg/kg, produced at most 50% antagonism of both the cathinone cue and of the ability of amphetamine to substitute for cathinone. It is suggested that the evidence for dopaminergic mediation of the cue properties of cathinone and of other CNS stimulants is somewhat tenuous, whilst endogenous phenylethylamine may play some part in the mediation of the stimulant cue. Haloperidol, alone and in conjunction with amphetamine or cathinone, produced a remarkable tendency for subjects to emit a greater proportion of their total responses on the inoperative rather than the operative lever than was seen after saline or injections of vehicle. This action of a neuroleptic drug suggests, in accordance with Colpaert, Niemegeers and Janssen (1977), that in drug discrimination antagonism studies involving neuroleptics, and perhaps other drugs, quantal (lever selection) rather than quantitative (percentage of responses on the drug lever) indices may be the procedures of choice.

Alkaloids↗

PubMed1986

Development of the discrimination of spatial phase in infancy.

The ability to discriminate grating patterns, containing the same spatial frequency components but in different phase relationships, has been studied in infants by comparing looking times following habituation to one pattern. The performance of 1-month-olds was compared with that of 2/3-month-old infants. Both age groups could discriminate a set of components in square-wave-phase (fundamental 0.18 c/deg) from components of the same amplitude combined in random phase. However, these compounds differ in peak-to-trough contrast, which infants of both ages could discriminate even for a constant waveform. When contrast was randomized from presentation to presentation, the older group still demonstrated discrimination, implying that they were sensitive to the pattern differences, but the younger group did not. The younger group also failed to demonstrate discrimination between the two waveforms when they were of fixed, matched, peak-to-trough contrast, indicating that the previous absence of discrimination was not simply due to distraction by the contrast variations. We conclude that 1-month-olds are insensitive to the configuration of these compound grating patterns even when they are capable of detecting their components. This loss of spatial information has some analogies with adult peripheral and amblyopic vision. Like other aspects of vision, it shows striking development between 1 and 3 months of age.

Aging↗

PubMed1986

Effect of acute administration of prazosin on blood pressure, heart rate and plasma renin level in the conscious normotensive rat.

This study investigated whether the specific alpha-antagonist, prazosin, stimulated basal plasma renin levels and heart rate. Furthermore the beta-adrenergic nervous system was also investigated to ascertain whether it was involved in this effect. Prazosin (0.1 or 1 mg/kg) was injected subcutaneously (s.c.) to conscious normotensive rats, either alone or in combination with the beta-adrenoceptor antagonist, DL-propranolol (1 or 3 mg/kg). Rats bore chronically implanted dorsal aorta cannula for measurement of blood pressure and heart rate and blood sampling for renin determinations. Acute administration of prazosin (1 mg/kg, s.c.) produced a fall in mean arterial pressure accompanied by renin release and tachycardia. A tenfold lower dose of prazosin did not alter blood pressure or heart rate but did stimulate renin release. Acute administration of DL-propranolol, (1 or 3 mg/kg, s.c.) produced falls in blood pressure and heart rate but did not affect plasma renin level. Combinations of prazosin with propranolol gave falls in blood pressure similar to those predicted on the basis of a simple addition of the effects of the two drugs given separately. Prazosin-induced tachycardia and renin release were attenuated by propranolol. It appears that prazosin produces renin release and tachycardia via stimulation of the beta-adrenergic adrenoceptor.

Animals↗

PubMed1986

Effects of inhaled oxitropium and fenoterol, alone and in combination, in chronic airflow obstruction.

Twenty-four elderly male patients with moderate-to-severe chronic airway obstruction took part in a double-blind, placebo-controlled, randomized dose-response and response-duration comparison of a new inhaled anticholinergic bronchodilator oxitropium bromide and the inhaled beta-agonist bronchodilator fenoterol hydrobromide. On 6 separate days lung function changes and side effects were monitored for 8 h after either placebo, oxitropium 100, 200 and 300 micrograms, fenoterol 400 micrograms, or oxitropium 200 micrograms plus fenoterol 400 micrograms. Fenoterol alone and in combination with oxitropium produced a rapid peak effect (mean delta FEV1 = 41.6 and 39.5%, respectively at 30 min). Oxitropium alone had a slow onset of action (peak delta FEV1 seen at 120 min: 100 micrograms = 22.7%, 200 micrograms = 29.9%, 300 micrograms = 28.2%). However, mean FEV1 remained within 5% of peak for 60 min after fenoterol, but for 180 min after each dose of oxitropium and after fenoterol plus oxitropium. No differences between oxitropium 200 and 300 micrograms were seen; however, these doses produced more prolonged bronchodilatation than did oxitropium 100 micrograms. The fenoterol-plus-oxitropium combination produced even more prolonged bronchodilatation. The only side effect, seen with each inhaler was a mildly unpleasant taste. No anticholinergic effects were seen. We conclude that oxitropium is an effective bronchodilator with slow onset but prolonged duration of action. In combination with fenoterol it produced both rapid and prolonged bronchodilatation in patients with chronic airflow obstruction.

Administration, Inhalation↗

PubMed1986

Oxitropium bromide. Dose-response and time-response study of a new anticholinergic bronchodilator drug.

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100 micrograms, 200 micrograms, and 300 micrograms) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400 micrograms), and a combination of oxitropium (200 micrograms) and fenoterol (400 micrograms). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced expiratory volume in one second [FEV1] remained within 5 percent of peak FEV1 for three hours, compared to one hour). Oxitropium in the 100 micrograms dose was inferior to 200 micrograms and 300 micrograms in subjective efficacy scores, peak percent change in FEV1, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200 micrograms and 300 micrograms. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200 micrograms. Addition of oxitropium to fenoterol appears to offer even greater efficacy.

Aged↗

PubMed1986

[Reduced sensitivity to noradrenaline and electric stimulation of the caudal artery of the aged rat].

UNLABELLED: Whilst arterial noradrenaline (NOR) content decreases with age (Waterson, et al. 1974; Neubauer and Christensen, 1978; Embree, et al., 1981), changes in vasoconstriction induced by NOR are equivocal (Tuttle, 1966; Cohen and Berkowitz, 1976; Scott and Reid, 1982; Duckles, et al., 1985). We have investigated changes in responsiveness to NOR in the NOR-rich rat tail artery. Two cm segments of the proximal tail artery from male Ivanos rats of 6/7, 16/17 or 30/31 months were perfused/superfused with Krebs bicarbonate (4 ml/min). Changes in perfusion pressure (mmHg) were determined after (1) electrical stimulation (1 to 30 Hz, 0.3 msec, 15 sec at supramaximal voltage, ES) followed by (2) perfusion with exogenous NOR (1 nM to 10 microM for 2 min at each concentration). Responses to ES were abolished by pretreatment with reserpine (2.5 mg/kg, i.p. at - 18 h) or perfusion with phentolamine (4 microM). They were produced therefore, by liberation of endogenous NOR. Arterial NOR content was determined by HPLC-EC following perchloric acid digestion (0.1 N). RESULTS: (Table: see text). Asterisks refer to t-test with 6/7 months age group (p less than 0.05, p less than 0.01 and p less than 0.001]. There were no differences in basal perfusion pressure before stimulation or in plateaux responses to maximal concentrations of NOR. In conclusion our results show a decrease in arterial NOR and in sensitivity to both endogenous and exogenous NOR with age.

Aging↗

PubMed1985

Attenuation of the baroreceptor reflex by general anesthetic agents in the normotensive rat.

We have investigated the effects of urethane, a urethane + allobarbital mixture, alpha-chloralose and sodium pentobarbital on baroreceptor reflex function in the normotensive rat. Results were compared to those obtained in the conscious rat. Baroreceptor reflex function was evaluated from the fall in heart rate which accompanied the rise in diastolic arterial pressure following intravenous administration of phenylephrine. All four anesthetic agents attenuated reflex function as shown by a decrease in the bradycardiac response. There was a four to five-fold attenuation with urethane and urethane + allobarbital and a two- to three-fold attenuation with alpha-chloralose and sodium pentobarbital.

Anesthetics↗

PubMed1985

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: evidence for spare myocardial beta receptors.

We have compared and contrasted the actions of (-)isoproterenol and (+/-) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5'-(beta, gamma imino) triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0 X 10(-7) M and 5.5 X 10(-8) M for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0 X 10(-7) and 3.5 X 10(-8) M for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5 X 10(-7) M and 1.7 X 10(-8) M for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗