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Biomedical subjects

A Barnett

Publications and source records attributed to A Barnett.

At least 91 records · Page 5Linked to original sources
PubMed1988

Characterization of the radioiodinated analogue of SCH 23390: in vitro and in vivo D-1 dopamine receptor binding studies.

A new radioiodinated molecule, 125I-SCH 38840 (previously referred to as 125I-SCH 23982), has been recently reported to be a D-1 dopamine receptor ligand. The current study confirms and expands the characterization of both the radiolabeled and unlabeled forms of this compound, as well as describing the development of an in vivo D-1 receptor binding assay utilizing the 125I-SCH 38840. The binding of 125I-SCH 38840 to rat striatal membranes, in vitro, was saturable and exhibited a KD of 1.47 nM. Competition studies using 125I-SCH 38840 exhibited a pharmacological profile consistent with the proposal that 125I-SCH 38840 was binding to the D-1 receptor. Further studies with the unlabeled SCH 38840 demonstrated that it inhibited dopamine-stimulated adenylate cyclase with a KI of 66.1 nM, indicating that SCH 38840 was acting as a D-1 antagonist. Behavioral studies demonstrated that SCH 38840 (MED = 1.0 mg/kg, s.c.) blocked conditioned avoidance responding in rats, a measurement considered predictive of anti-psychotic activity in man. In vivo binding of 125I-SCH 38840 to rat striatum following s.c. administration was specific. Peak striatal levels were observed 1 h after injection, with measurable binding observed out to 8 h post-treatment. The displacement of the in vivo binding by unlabeled standards again suggested a D-1 selective interaction. The half-life of the in vivo binding of 125I-SCH 38840 was approximately 1.25 h, and was nearly equivalent to the half-life of the anti-CAR activity of unlabeled SCH 38840. These results clearly demonstrate the D-1 nature of SCH 38840's behavioral activity and strengthen the anti-psychotic potential of a D-1 antagonist.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Selective affinity of the benzodiazepines quazepam and 2-oxo-quazepam for BZ1 binding site and demonstration of 3H-2-oxo-quazepam as a BZ1 selective radioligand.

Quazepam and 2-oxo-quazepam are novel benzodiazepines containing a trifluoroethyl substituent on the ring nitrogen at position #1. Detailed competition binding experiments (25 to 30 concs.) at 4 degrees C were undertaken with these compounds versus 3H-flunitrazepam using synaptic membranes from rat cortex or cerebellum. Unlike other benzodiazepines, both quazepam and 2-oxo-quazepam distinguished two populations of 3H-flunitrazepam binding sites in rat cortex which were present in roughly equal proportions and for which the compounds displayed a greater than 20-fold difference in affinity. In cerebellum, no such discrimination of sites was noted for 2-oxo-quazepam, but quazepam did distinguish a small, low affinity (15% of total) population of sites. 3H-2-oxo-quazepam was prepared and used in competition studies to substantiate the conclusion that these compounds discriminate two populations of benzodiazepine sites in rat cortex. This new radioligand was shown to specifically label BZ binding sites with high affinity in a saturable manner. The competition experiments were then conducted using 3H-2-oxo-quazepam at a radioligand concentration sufficiently low (0.5 nM) to ensure that only the higher affinity binding sites which 2-oxo-quazepam discriminates would be occupied. Competition experiments in both cortex and cerebellum under these conditions indicated single site binding for unlabelled quazepam and 2-oxo-quazepam in every instance. This suggests that 3H-2-oxo-quazepam should be a useful new tool for selectively labeling and studying the BZ1 population of benzodiazepine binding sites.

Animals↗
PubMed1988

Serotonergic component of SCH 23390: in vitro and in vivo binding analyses.

A series of benzazepines related to SCH 23390 were tested for binding to the 5HT-2 receptor. The compounds tested inhibited the binding of 3H-ketanserin with KI values generally greater than those observed for the D-1 receptor, but less than those for the D-2 receptor. When this serotonergic activity was correlated to the D-1 activity, the resulting coefficient was 0.84, indicating a strong correlation between the two activities. Conversely, the 5HT-2 activity did not show a good correlation with the D-2 activity. To further test the significance of the 5HT-2 binding of the SCH 23390, in vivo binding studies were performed using 125I-SCH 38840 in the frontal cortex, an area containing both D-1 and 5HT-2 receptors. The in vivo binding of 125I-SCH 38840 to frontal cortex exhibited peak levels one hour following subcutaneous administration, similar to the time course previously observed in striatum. The binding was both D-1 and tissue specific. Competition studies with selected standards demonstrated that inhibition of the binding to frontal cortex, in contrast to the inhibition observed in the striatum, exhibited a Hill coefficient less than unity, implying interaction at more than one receptor subtype. When SCH 23390 and ketanserin were administered simultaneously, the inhibition of the in vivo binding of 125I-SCH 38840 to striatum was not different than that observed with SCH 23390, alone. However, the inhibition of binding to frontal cortex was significantly greater than that demonstrated with either SCH 23390 or ketanserin, alone, suggesting that 125I-SCH 38840 was binding to both D-1 and 5HT-2 receptors, in vivo.

Animals↗
PubMed1988

Systemic effects resulting from topical ocular administration of SCH 33861, a novel ACE inhibitor ocular hypotensive agent.

SCH 33861 (7- N- 1(S)-(Carboxy)-3-phenylpropyl -(S)-alanyl 1,4-dithia-7-azaspiro 4.4 nonane-8(S)-carboxylic acid) is a novel, non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with marked topical ocular hypotensive activity. The present study evaluated the degree of systemic ACE inhibition resulting from topical administration of 0.01 and 0.1% concentrations (10 and 100-fold greater than needed to lower IOP) of SCH 33861 in conscious rabbits. For reference purposes, captopril, a prototype ACE inhibitor, was examined at concentrations 5 and 20-fold greater than needed to lower IOP. Neither 0.01 nor 0.1% topical SCH 33861 led to inhibition of pressor responses to 0.3 micrograms/kg iv challenges with angiotensin I (AI) over a 4 hr period. Captopril, in contrast, caused significant attenuation of AI pressor responses. The magnitude and duration of systemic ACE inhibition following captopril administration was concentration related. Intravenous administration of the same dose administered topically did not cause any systemic ACE inhibition with 0.01% SCH 33861. Following iv 0.1% SCH 33861, 0.5 or 2.0% captopril, AI responses were inhibited 60-70% indicating the ability to inhibit ACE if any systemic absorption took place. Topical administration of 0.01% SCH 33861 twice daily for five days also did not produce systemic ACE inhibition. These findings indicate that topical amounts of SCH 33861 greatly in excess of those needed to effect reductions in IOP have an exceptionally low potential for producing systemic effects.

Administration, Topical↗
PubMed1988

gamma-Aminobutyric acid and pentobarbital enhance 2-[3H]oxoquazepam binding to type I benzodiazepine recognition sites in rat and human brain.

2-Oxoquazepam (2oxoquaz) is a novel benzodiazepine which shows preferential affinity for type I benzodiazepine recognition sites. In the present study, we analyzed the effect of gamma-aminobutyric acid (GABA), pentobarbital, and chloride ions on [3H]2oxoquaz and [3H]flunitrazepam ( [3H]FNT) binding to membrane preparations from rat and human brain. GABA stimulated [3H]-2oxoquaz and [3H]FNT binding in a concentration-dependent manner. The maximal enhancement produced by GABA on [3H]2oxoquaz binding was higher than that produced on [3H]FNT binding in both rat and human tissues. In the rat brain, the effect of GABA on [3H]2oxoquaz was similar throughout different brain areas, whereas the effect on [3H]FNT binding was lower in the cerebral cortex and hippocampus than in the cerebellum. Moreover, both [3H]2oxoquaz and [3H]FNT binding were stimulated by chloride ions and pentobarbital. The results are consistent with the hypothesis that type I benzodiazepine recognition sites are linked functionally to the GABA recognition site and the chloride ionophore.

Adult↗
PubMed1988

Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity.

SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl- 5H-benzo[d]naptho-(2,1-b)azepine] is a benzonaphthazepine that has been evaluated as a selective D1 dopamine receptor antagonist. In vitro, SCH39166 (Ki = 3.6 nM) inhibited the binding of [3H]SCH23390 (a D1 specific compound) and blocked dopamine-stimulated adenylate cyclase (Ki = 9.1 nM); in contrast the Ki for SCH39166 to displace [3H]spiperone (D2) was greater than 1 microM and its Ki vs. [3H]-ketanserin (5-hydroxytryptamine2) binding was greater than 300 nM. In vivo, SCH39166 inhibited both rat and squirrel monkey conditioned avoidance responding (minimal effective dose = 10 and 1.78 mg/kg p.o., respectively) and had a duration of at least 6 hr in both species. In addition, SCH39166 antagonized apomorphine-induced stereotypy in rats (minimal effective dose = 10 mg/kg p.o.). These in vivo actions of SCH39166 are similar to the activity of typical dopamine antagonists. However, in contrast to D2-selective antagonists, SCH39166 failed to increase plasma prolactin levels, did not block apomorphine-induced emesis in the dog and had minimal effects on the striatal levels of homovanillic acid or dihydroxyphenylacetic acid. Furthermore, although immobility was seen after p.o. administration of SCH39166 using the inclined screen test, the drug did not cause catalepsy at doses up to 10 times its minimal effective dose in the rat conditioned avoidance response test. Additionally, SCH39166 inhibited apomorphine-induced climbing at lower doses than it inhibited apomorphine-induced sniffing in mice. The results from these latter two tests suggest that SCH39166 may have a reduced liability to produce extrapyramidal side effects. Therefore, based on this profile of activity, SCH39166 is a selective D1 dopamine receptor antagonist both in vitro and in vivo. Additionally, because this compound is longer acting in the primate than previously available D1 antagonists, it has potential utility as a clinically useful drug.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic.

SCH 34826 [(S)-N-[N-[1-[[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine]-beta-alanine] was synthesized as a p.o. active prodrug enkephalinase inhibitor. In vivo, it is de-esterified to SCH 32615 (N-[L-(-1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), the active constituent. In vitro, the Ki for SCH 32615 to block the degradation of Met5-enkephalin by isolated enkephalinase is 19.5 +/- 0.9 nM. In contrast, SCH 32615 did not inhibit aminopeptidase or diaminopeptidase III degradation of Met5-enkephalin up to 10 microM and did not affect angiotensin converting enzyme up to 10 microM. In vivo, p.o. administered SCH 34826 potentiated the analgesic effects of D-Ala2-Met5-enkephalinamide in mice (ED50 = 5.3 mg/kg p.o.) and rats [minimal effective dose (MED) = 1 mg/kg p.o.]; SCH 32615 had no effect up to 30 mg/kg p.o., but was active parenterally (ED50 in mice = 1.4 ng/kg sc). Direct, naloxone-reversible analgesic effects of SCH 34826 were demonstrated in the mouse low temperature hot-plate test (MED = 30 mg/kg p.o.), the mouse acetic acid-induced writhing test (MED = 30 mg/kg p.o.), the rat stress-induced analgesia test (MED = 10 mg/kg p.o.) and the modified rat yeast-paw test (MED = 100 mg/kg p.o.). Using the rat D-Ala2-Met5-enkephalinamide potentiation test the duration of action of SCH 34826 was at least 4 hs. No respiratory or gastrointestinal side effects of any consequence were noted at doses up to 100 times those active in the D-Ala2-Met-5-enkephalinamide potentiation test.

Administration, Oral↗
PubMed1988

Protective action of SCH 12223 against experimentally induced gastric and intestinal lesions.

The gastrointestinal protective action of SCH 12223 [3-(n-butyl)-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one hydrate, sodium salt] against various noxious stimuli was characterized in rats. SCH 12223 inhibited the ethanol-induced gastric lesions when given p.o. (0.3-3 mg/kg) or i.v. (1 and 3 mg/kg). Indomethacin pretreatment (10 mg/kg p.o.) did not interfere with this effect. SCH 12223 was also active p.o. in five gastric erosion models: aspirin (1-10 mg/kg), aspirin + acid (1-30 mg/kg), indomethacin (1-10 mg/kg), stress (1 and 3 mg/kg) and reserpine (0.3-10 mg/kg)-induced erosions. The compound lacked antisecretory activity in the pylorus-ligated rats (10 mg/kg p.o.) but increased total gastric mucus (N-acetylneuraminic acid measurements) (1-10 mg/kg p.o.). SCH 12223 (10 and 30 mg/kg p.o.) attenuated intestinal lesions provoked by indomethacin (20 mg/kg p.o. or s.c.) and the protected animals showed better weight gain and food intake than controls. In a 38-day study, SCH 12223 also improved survival from indomethacin lethality (6 of 16 vs. 16 of 16 in the control, P less than .05). The protection cannot be attributed to changes in biliary excretion and plasma levels of indomethacin. We conclude that SCH 12223 is a unique agent which protects both gastric and intestinal epithelia from noxious stimuli, a feature shared by prostaglandins.

Administration, Oral↗
PubMed1987

Topical ocular hypotensive effects of the novel angiotensin converting enzyme inhibitor SCH 33861 in conscious rabbits.

SCH 33861 is a novel, non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor. Topical administration of the compound to the eye of conscious rabbits was employed to examine actions on intraocular pressure (IOP). Falls in IOP resulted from SCH 33861 (0.001-0.01%) administration. Ocular hypotensive responses were sustained for as long as 24 hrs following a single application of 0.001% SCH 33861. The RSS isomer of SCH 33861, which is 200-fold weaker an ACE inhibitor than SCH 33861, caused only transient falls in IOP at 0.1% concentration. The magnitude of the fall in IOP induced by 0.001% SCH 33861 (4.8 +/- 0.5 mmHg) was comparable to that produced by 0.5% timolol (4.5 +/- 0.3 mmHg). Other ACE inhibitors such as captopril (0.1%) and enalaprilic acid (0.01%) also reduced IOP by 4.0 +/- 0.4 and 4.7 +/- 0.4 mmHg, respectively. These findings indicate that SCH 33861 is 500-fold more potent on a weight basis than is timolol in lowering IOP. No loss of ocular hypotensive activity was observed when SCH 33861 was administered twice daily for 5 days suggesting little, if any, potential for tolerance development. SCH 33861, as well as the other ACE inhibitors, caused neither ocular irritation nor alteration of pupil diameter. These findings suggest that inhibition of ocular ACE may represent an effective means of reducing IOP.

Administration, Topical↗
PubMed1987

Molecular biology of the genes for immobilization antigens in Paramecium.

Several genes for surface antigens of the Paramecium aurelia complex of species have been isolated. In addition to known deletions of the 51A gene, we have obtained deletions involving the 51B gene and have developed a procedure for obtaining deletions of additional genes. Both Mendelian and non-Mendelian deletions of both the A and B genes have been found. In the non-Mendelian deletions the genes are present in the micronuclei and absent in the macronuclei. Processing of micronuclear DNA into new macronuclear DNA at conjugation and autogamy is under the control of the old macronucleus, and newly forming macronuclei become exactly like the old. Thus in the non-Mendelian mutants, macronuclei have a specific antigen gene deleted and also are impaired in their ability to direct normal DNA processing at the next conjugation or autogamy. These cases, along with others, show that this system of macronuclear control is a fundamental feature of ciliate genetics. The sequence of the 51A and 51C genes is described and compared with the 156G and 51H genes obtained by others. The 51A and 156G genes are remarkably similar while 51C and 51H are rather different. No introns or pseudogenes have been observed. Some, possibly all, of the genes are on the ends of chromosomes. Characteristic upstream and downstream sequences adjacent to the coding portions of the genes are given. The sequences UAA and UAG are preferred over CAA and CAG for glutamine while UGA is the true stop codon.

Animals↗
PubMed1986

Relative activities of SCH 23390 and its analogs in three tests for D1/DA1 dopamine receptor antagonism.

Inhibitory activities of a series of analogs of SCH 23390 ((R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine) in which the 7-chloro group was substituted by bromo, fluoro, methyl and methoxy groups, respectively, were compared in three tests for D1 and DA1 dopamine (DA) receptor antagonism: inhibition of DA-induced renal vasodilation in the anesthetized dog (DA1 receptor model), inhibition of DA-stimulated adenylate cyclase in the striatum of adult female rats (D1 receptor model) and displacement of [3H]SCH 23390 in the striatal homogenates of male rats. In addition the D2 receptor affinity of each of the compounds chosen was assessed via displacement of [3H]spiperone binding from rat striatum. S-enantiomers of the Cl and CH3 analogs were 200- to 700-fold weaker than the respective R-enantiomers in all three tests. The activity of all the R-enantiomers was in the nanomolar range and varied no more than 8-fold in all three tests. The F analog in the ligand binding test was the only exception, which was 30-fold weaker than the C1 analog. All of the R-enantiomers studied showed much weaker affinity for the D2 receptor, as assessed by displacement of [3H]spiperone binding. Similar enantiomer selectivity and parallel affinities of the R-enantiomers in the prototype models for D1 and DA1 receptors strengthen the evidence in support of identity between the D1 and DA1 dopamine receptors. These results further indicate that displacement of SCH 23390 in the ligand binding test reflects affinity of a compound for D1 and DA1 dopamine receptors.

Adenylyl Cyclases↗
PubMed1986

Selective displacement of [3H]mepyramine from peripheral vs. central nervous system receptors by loratadine, a non-sedating antihistamine.

Displacement of [3H]mepyramine binding was compared in membranes from guinea-pig lung vs. cerebral cortex as a measure of affinity for peripheral vs. central nervous system (CNS) histamine receptors. Loratadine, a new non-sedating antihistamine, was found to be the only compound tested which was selective for lung (Ki = 35 nM) vs. cortex (Ki = 118 nM). This difference is statistically significant (P less than 0.05) whereas there was no significant (P greater than 0.05) difference in the Kis between the 2 tissues for terfenadine, astemizole, mequitazine or chlorpheniramine. It is concluded from these and other studies that the lack of significant sedative effects shown with loratadine is due to its poor penetration into the CNS and selectivity for peripheral histamine receptors.

Aminopyridines↗
PubMed1986

Relationships of brain and plasma levels of quazepam, flurazepam, and their metabolites with pharmacological activity in mice.

The relationships between the pharmacological activities of quazepam and flurazepam and the concentrations of each drug and its major active metabolites in brain and plasma following single oral doses of either drug to mice were investigated. At various time points after either quazepam or flurazepam administration, pharmacological activity was measured by the inhibition of electroconvulsive shock (ECS)-induced seizures. After quazepam, the plasma and brain samples obtained at the same time points were assayed for concentrations of quazepam, 2-oxoquazepam and N-desalkyl-2-oxoquazepam by specific GLC methods. After flurazepam, the plasma and brain samples were assayed for flurazepam, hydroxyethyl-flurazepam, and N-desalkyl-2-oxoquazepam, also by specific GLC methods. The results showed that both quazepam and flurazepam were rapidly metabolized and that parent drugs and metabolites were rapidly distributed to the brain. The brain levels of all the benzodiazepines analyzed in this study paralleled plasma levels. After quazepam, pharmacological activity most closely paralleled the combined brain concentrations of quazepam and 2-oxoquazepam rather than N-desalkyl-2-oxoquazepam levels. In contrast, following the flurazepam dose, activity most closely paralleled N-desalkyl-flurazepam concentrations. From these data, it can be concluded quazepam is distinctly different from flurazepam, and that, in the presence of quazepam and 2-oxoquazepam, N-desalkyl-2-oxoquazepam does not contribute extensively to the observed pharmacological activity.

Animals↗
PubMed1986

Interaction studies in mice of SCH 29851, a potential non-sedating antihistamine, with commonly used therapeutic agents.

SCH 29851 was studied for its ability to interact with selected drugs used in man. The non-sedating antihistamine terfenadine and the sedating antihistamine diphenhydramine were also studied for comparison. SCH 29851 at 80 mg/kg po in mice, a dose about 50 times its ED50 for blocking histamine-induced paw edema in the same species, potentiated the anticonvulsant effects of diazepam. At the high dose of 320 mg/kg po, about 80 times its ED50 for antihistamine effects, SCH 29851 potentiated the ability of high doses of ethanol and hexobarbital to induce loss of righting reflexes (LRR). However, no potentiation was seen when SCH 29851 was studied with lower doses of ethanol or phenobarbital that had anticonvulsant effects but did not cause LRR. At this high dose of 320 mg/kg po, SCH 29851 also did not interact with the antihypertensive drugs propranolol and alpha-methyldopa, the anti-ulcer drug cimetidine, the nasal decongestant pseudoephedrine, or the CNS stimulant d-amphetamine. A nearly identical profile of interactions was seen with terfenadine, including potentiation of diazepam at 50 times its antihistamine ED50, potentiation of ethanol- and barbiturate-induced LRR at 80 times its antihistamine ED50, and lack of interaction effects at 320 mg/kg po with each of the other tested drugs. The demonstration in this study of the significant interactions between diphenhydramine and many of the tested drugs is consistent with the clinical experience in man that this drug does have sedating properties and significant interactions with drugs like ethanol and diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A concentration gradient of bacteria within wound tissues and scab.

This investigation was designed to evaluate the effect of a synthetic moisture vapor permeable dressing on the size of the bacterial population of superficial wounds. Split-thickness donor sites were created in pig skin and were treated with a synthetic occlusive dressing (Tegaderm), with fine mesh gauze, or with nothing. All wounds became spontaneously infected with a variety of bacteria, predominantly with Staphylococcus epidermidis. The population of the Tegaderm wounds was always greater than that of the untreated controls, while that of the gauze treated wounds was equal to or less than that of the controls. Tegaderm dressed wounds healed more quickly than did the others. A gradient in the concentration of bacteria within the wounds was seen, with a very high concentration in the scab (10(8) cells/g), an intermediate concentration (10(6) cells/g) in the dermal layer, and the lowest concentration (10(4) cells/g) in the hypodermal level of the wound tissue. Such a gradient has not previously been reported. No evidence was seen that the level of infection declined over time for any of the dressings. Apparent bacterial clearing in earlier investigations may be due to the progressive loss of superficial wound tissues with the corresponding exclusion of the high concentration of bacteria within these layers from the tissue sampled.

Animals↗
PubMed1986

Facial form analysis of the lower and middle face.

Structural form analysis identifies the major structural members of the middle and lower face through their high- and low-light areas, provides measurements and relationships between the key points, and explains the angular relationships in constructing a geometric form corresponding to these members. The six key points define the superior and inferior and anterior and posterior angles. The angles and planes then lead to a geometric form of the lower and middle face. The final construction provides a framework for examining the facial form and making aesthetic judgments which lead directly to surgical decisions. A study of 50 Caucasian women ages 22 to 30 was performed. Specific patient examples with analyses are provided.

Adult↗
PubMed1986

Haemodynamic and hormonal responses to exercise: studies in patients with diabetes mellitus and adrenomedullary deficiency.

The haemodynamic and hormonal responses of patients with autonomic neuropathy and others with adrenomedullary deficiency were compared with mild hypertensives (range of blood pressure 90-100 mmHg diastolic and 140-160 mmHg systolic) and uncomplicated diabetics during standard exercise and postural manoeuvres using continuous arterial blood pressure monitoring. There was no difference in these parameters between the groups when at rest or on standing. During exercise there was no significant difference in blood pressure and heart rate between the groups and all showed significant increases in plasma noradrenaline (mean rise for all groups 2730-22 105 pm 1(-1), P less than 0.03) and (in all but the adrenalectomized subjects) adrenaline (mean rise for remaining three groups 946-3384 pm 1(-1), P less than 0.03; adrenalectomized group showed no rise). The group with autonomic neuropathy showed a significant rise in plasma cortisol from basal 450 +/- 40 to 845 +/- 72 nm 1(-1), P less than 0.005 after exercise, but the other groups showed no significant change. The maximum level attained for plasma cortisol in the adrenalectomized subjects after exercise was significantly less (260 +/- 41 nm 1(-1) than in the diabetic groups (696 +/- 68 nm 1(-1) (non-neuropaths), 845 +/- 72 nm 1(-1) (neuropaths), P less than 0.01). We have demonstrated normal blood pressure and pulse responses to posture and sustained exercise in diabetics with autonomic neutropathy. The findings of similarly normal responses in patients with adrenomedullary deficiency suggest that circulating adrenaline is not obligatory to a normal haemodynamic response to exercise.

Adrenal Insufficiency↗