bluuebunny/crossref_metadata_2025 huggingface dataset:
α1-Adrenoceptor Blockade: Dissociation of Its Effects on Renin Release and Arterial Blood Pressure in Man
Authors: Morganti A. , Sala Carla , Palermo Anna , Turolo Lucia , Zanchetti A.
Published: August 2015

1. The possibility that the juxtaglomerular α1-adrenoceptors mediate an inhibitory action on renin release in man was examined in seven patients with essential hypertension, by measuring (i) the acute effects of prazosin (0.25 mg intravenously), a selective α1-adrenoceptor-blocking agent, on arterial pressure and plasma renin activity, the degree of α-blockade induced by the drug being assessed by comparing the pressor response with that to a test dose of phenylephrine before and after prazosin administration, and (ii) the increases in plasma renin activity in response to isoprenaline before and during the prazosin-induced α-blockade.

2. Twenty minutes after the infusion of prazosin, when the pressor response to phenylephrine was reduced by 80% with respect to control, (i) mean arterial pressure was practically unchanged, (ii) plasma renin activity was almost doubled and (iii) the increases in plasma renin activity in response to isoprenaline were significantly greater, both in absolute and percentage values, than those observed before prazosin.

3. The increments in baseline plasma renin activity induced by prazosin in the absence of decrease in arterial pressure and the enhancement in renin responsiveness to the β-adrenoceptor stimulus suggest that, in man, the juxtaglomerular α1-adrenoceptors exert a direct, suppressive action on renin release.
Chemical Renal Medullectomy; Effect upon Reversal of Two-Kidney, One-Clip Hypertension in the Rat
Authors: Bing R. F. , Russell G. I. , Swales J. D. , Thurston H. , Fletcher A.
Published: August 2015

1. Chemical renal medullectomy was produced in rats by injection of 2-bromoethylamine hydrobromide. Plasma creatinine and blood pressure were unchanged although urine volume was increased fourfold.

2. Left renal artery constriction resulted in similar degrees of hypertension in both intact and medullectomized rats. This was associated with a significantly smaller rise in plasma renin concentration in the latter.

3. Blood pressure in conscious intact hypertensive rats became normal within 24 h of unclipping whereas blood pressure of medullectomized rats remained significantly elevated.

4. The presence of an intact renal medulla is essential to the complete reversal of two-kidney, one-clip hypertension in the rat. This may reflect the loss of a medullary vasodepressor system.
β-Endorphin, An Endogenous Depressor Agent in the Rat?
Authors: Petty M. A. , Sitsen J. M. A. , De Jong W.
Published: August 2015

1. The role of opiates in cardiovascular regulation has been investigated.

2. In urethane-anaesthetized renal hypertensive rats (two-kidney, one-clip Goldblatt model), intracerebroventricular β-endorphin (10 μg) caused a greater fall in mean arterial pressure than in sham-operated controls.

3. Unilateral injection of β-endorphin into the nucleus tractus solitarii of the urethane-anaesthetized rat resulted in a U-shaped dose—response relationship, with a fall in mean arterial pressure and heart rate occurring at low doses. Doses above 10 ng caused a rise in pressure, accompanied by a variable effect on heart rate.

4. The fall in blood pressure and heart rate was prevented by prior subcutaneous administration of naloxone. Naloxone caused an increase in blood pressure when administered alone.

5. These results suggest a depressor role of an endogenous brain opiate, possibly β-endorphin; a site of action is probably the nucleus tractus solitarii.
Central Peptidergic Stimulation in Blood Pressure Control: Role of Enkephalins in Rats
Authors: Yukimura T. , Unger T. , Rascher W. , Lang R. E. , Ganten D.
Published: August 2015

1. The central blood pressure effects of the enkephalin analogue, d-Ala2-Met-enkephalin were investigated in normotensive rats and in spontaneously hypertensive rats.

2. In conscious Wistar rats, injection of 1.7, 17 and 170 nmol of d-Ala2-Met-enkephalin into the lateral brain ventricle produced dose-dependent blood pressure increases of 5.3 ± 1.8, 10.5 ± 2.8 and 15.3 ± 3.0 mmHg respectively. In contrast, in α-chloralose-anaesthetized rats, the same doses of the enkephalin analogue produced dose-dependent blood pressure falls of −8.9 ± 1.9, −11.1 ± 5.2 and −19.8 ± 8.4 mmHg.

3. The pressor responses to 170 nmol of d-Ala2-Met-enkephalin were blocked by intracerebroventricular pretreatment with the opiate receptor antagonists diprenorphine and naloxone at doses of 10–500 nmol. The depressor effects under anaesthesia were blocked by diprenorphine (10–100 nmol) but not by naloxone.

4. Spontaneously hypertensive rats showed enhanced pressor responses to centrally applied enkephalin when compared with normotensive rats.

5. Central injection of diprenorphine alone produced an initial short blood pressure increase followed by a long-lasting blood pressure fall, which was significantly greater in spontaneously hypertensive rats than in normotensive rats.

6. The results indicate that the central blood pressure effects of enkephalins depend on the state of consciousness and are mediated through naloxone- and diprenorphine-sensitive opioid receptors.

7. The increased sensitivity to centrally applied enkephalins and the depressor responses to the intracerebroventricular injection of diprenorphine suggest a central enkephalinergic contribution to the maintenance of hypertension in spontaneously hypertensive rats.
Does Long-Term Low-Dose Corticosteroid Therapy Cause Hypertension?
Authors: Jackson S. H. D. , Beevers D. G. , Myers K.
Published: August 2015

1. One hundred and ninety-five patients undergoing low-dose prednisone or prednisolone therapy were investigated. Blood pressure, weight, serum urea, sodium and potassium were recorded before therapy and again after at least 1 year of therapy.

2. The rise in both mean systolic and mean diastolic blood pressure was paralleled by an increase in the prevalence of arbitrarily defined hypertension.

3. There was no relationship between change of blood pressure and either dose of corticosteroid or duration of therapy. Blood pressure before therapy was the main determinant of the change in blood pressure.

4. Mean serum sodium levels rose slightly but serum potassium levels did not change during the follow-up period. There was no significant weight gain.

5. These results indicate that treatment of asthma and rheumatoid arthritis with prednisolone or prednisone in low dose does not cause hypertension or biochemical features suggestive of mineralocorticoid excess.
Neurohumoral Response to Hospitalization in Hypertensive Patients
Authors: De Leeuw P. W. , Van Soest G. A. W. , Punt R. , Hoogma R. P. L. M. , Smout A. J. P. M. , Birkenhäger W. H.
Published: August 2015

1. To investigate whether reduced activity of pressor systems could explain the spontaneous drop in pressure upon hospitalization, 51 subjects with uncomplicated essential hypertension were admitted to hospital. Sodium intake was fixed at 55 mmol/day.

2. Blood samples for noradrenaline, adrenaline, active renin, angiotensin II and aldosterone were drawn on each morning of the first 3 days of hospitalization; blood pressure was measured at 2 h intervals and values were averaged for each day.

3. Subjects were divided in two groups depending on whether they became normotensive (group 1; n = 12) or remained hypertensive (group 2; n = 39). This distinction was thought to reflect mild and more severe hypertensive groups respectively.

4. Although both groups showed a comparable fall in blood pressure during hospitalization, noradrenaline levels fell more consistently in group 1, whereas adrenaline levels fell only in group 2. The components of the renin—angiotensin—aldosterone system rose, but more conspicuously in group 1.

5. It is concluded that withdrawal of sympathetic activity can only partly explain the hypotensive response to hospitalization. The renin—angiotensin system behaves only passively and appears to be counterproductive to alterations in blood pressure.
Metoprolol and Pindolol in Hypertension: Different Effects on Peripheral Haemodynamics
Authors: Svensson A. , Gudbrandsson T. , Sivertsson R. , Hansson L.
Published: August 2015

1. Thirty-six patients with essential hypertension, were randomly allocated to double-blind treatment with either metoprolol (100–200 mg/day) or pindolol (5–10 mg/day). The effects upon blood pressure and peripheral blood flow were determined. Both drugs reduced blood pressure significantly.

2. Heart rate was significantly reduced by metoprolol but not by pindolol.

3. Vascular resistance at maximal dilatation was not changed by either compound.

4. At rest, pindolol reduced vascular resistance in the calf by 14% (P < 0.05) but metoprolol tended to increase the resistance slightly. The difference in effect was also significant (P < 0.005).

5. During leg muscle work there were no changes in vascular resistance in the forearm with either compound.

6. We conclude that pindolol appears to reduce blood pressure at least partly through vascular mechanisms, in contrast to metoprolol. The response to sympathetic stimulation induced by physical exercise does not differ between metoprolol- and pindolol-treated patients.
β-Receptor-Blocking Agents May Reverse or Prevent Diuretic-Induced Increases in Serum Low-Density Lipoprotein Cholesterol
Authors: Meier A. , Schiffl H. , Weidmann P. , Mordasini R. , Riesen W. , Bachmann C.
Published: August 2015

1. The effect of treatment with a thiazide-like diuretic alone or combined with a β-adrenoceptor blocker on serum lipoproteins was investigated in 35 patients with essential hypertension.

2. In group I (18 patients), serum low-density lipoprotein cholesterol was increased (P < 0.001) during monotherapy with chlorthalidone (100 mg/day) but not during combined chlorthalidone-β-blocker therapy.

3. This tendency was similar in subgroups studied with an inverse sequence of drug administration. In subgroup IA (11 men), a 22% increase (P < 0.01) in low-density lipoprotein cholesterol after 6 weeks of chlorthalidone was reversed after use of a β-blocker as well as chlorthalidone; in subgroup IB (five men, two post-menopausal women), low-density lipoprotein cholesterol was increased by 41% (P < 0.05) above placebo values 6 weeks after withdrawal of the β-blocker from combination therapy.

4. In group II (18 men), low-density lipoprotein cholesterol was increased by 13% (P < 0.025) after 4 weeks of monotherapy with clopamide (5 mg/day) but restored to control levels 4 weeks after addition of pindolol (10 mg/day).

5. No significant changes occurred during any treatment phase in high-density lipoprotein cholesterol.

6. Certain β-receptor blocking agents may prevent or reverse diuretic-induced increases in serum low-density lipoprotein cholesterol.
Lack of Antagonism in the Antihypertensive Effects of Clonidine and Prazosin in Man
Authors: Andréjak M. , Fievet P. , Makdassi R. , Comoy E. , De Fremont J. F. , Coevoet B. , Fournier A.
Published: August 2015

1. In four patients, whose hypertension was not controlled (supine blood pressure > 150–90 mmHg) by addition of 5 mg/day of prazosin to previous treatment (diuretics and β-blockers), clonidine (150–450 μg/day) led to control of hypertension in three cases.

2. In ten patients whose hypertension was not controlled by a treatment including clonidine (300–450 μg/day), the progressive addition of prazosin to a maximal dose of 4–22.5 mg/day led to control of hypertension in nine cases (mean supine blood pressure decreased from 174–102 to 144–88 mmHg).

3. In 13 hospitalized patients, clonidine was abruptly interrupted whereas prazosin was continued. Mean blood pressure (± sem) rose from 145 ± 1/85 ± 2 to 169 ± 7/104 ± 5 mmHg 48 h after clonidine withdrawal whereas plasma noradrenaline and adrenaline rose from 328 to 758 pg/ml and from 75 to 137 pg/ml. No subjective symptoms were noted. There was a negative correlation between blood pressure increase and the dose of prazosin.

4. It is concluded that (a) there is no antagonism between clonidine and prazosin in their antihypertensive action in man when used at usual clinical doses, (b) a protective effect of prazosin against an eventual clonidine withdrawal syndrome is suggested by the negative correlation between blood pressure increase and the dose of prazosin.
Body-Fluid Composition in Normal and Hypertensive Man
Authors: Bauer J. H. , Brooks C. S.
Published: August 2015

1. Erythrocyte mass, plasma volume (PV), extracellular fluid volume (ECFV) and total body water were simultaneously measured in 30 normotensive and 30 normal-renin hypertensive Caucasian male subjects for accurate determination of the presence or absence of a disorder(s) in body-fluid composition in hypertension.

2. The results indicate that plasma volume and total blood volume are lower in hypertensive subjects than in normotensive control subjects. The PV comprised 19% of the ECFV in both control and hypertensive subjects.

3. ECFV was lower in hypertensive subjects than in normotensive control subjects; the PV and interstitial fluid components of the ECFV were reduced by similar proportions. The ECFV, furthermore, comprised a smaller portion of the total body water in hypertensive subjects than that in control subjects.

4. We conclude that in the hypertensive state there is a reduction in the ECFV, but that there is no change in the partition of the ECFV between the plasma and interstitial components.
Functional Interaction between Angiotensin and Sympathetic Reflexes in Cats
Authors: Hatton R. , Clough D. P. , Adigun S. A. , Conway J.
Published: August 2015

1. Lower-body negative pressure (LBNP) was used to stimulate sympathetic reflexes in anaesthetized cats. At −50 mmHg for 10 min it caused transient reduction in central venous pressure and systemic arterial blood pressure. Arterial blood pressure was then restored within 30 s and there was a tachycardia. Central venous pressure showed only partial recovery. The resting level of plasma renin activity (PRA; 2.9–3.2 ng h−1 ml−1) did not change until approximately 5 min into the manoeuvre.

2. When converting-enzyme inhibitor (CEI) was given 75 s after the onset of suction it caused a greater and more sustained fall in arterial blood pressure than when administered alone. The angiotensin II (ANG II) antagonist [Sar1,Ala8]ANG II produced similar effects after a short-lived pressor response.

3. This prolonged fall in arterial blood pressure produced by CEI was not associated with reduced sympathetic efferent nerve activity. This indicates that the inhibitor affects one of the peripheral actions of angiotensin and in so doing produces vasodilatation of neurogenic origin.

4. These findings suggest that angiotensin, at a level which does not exert a direct vasoconstrictor action, interacts with the sympathetic nervous system to maintain arterial blood pressure when homeostatic reflexes are activated. A reduction in the efficiency of these reflexes by CEI may contribute to its hypotensive effect.
The Effect of Knee Injury on the Number of Muscle Fibres in the Human Quadriceps Femoris
Authors: Young A. , Hughes I. , Round J. M. , Edwards R. H. T.
Published: August 2015

1. By means of ultrasound scanning, bilateral measurements of the cross-sectional area of the quadriceps muscle group were made in 14 young adults with unilateral thigh muscle wasting after knee injury. Needle biopsy specimens from the lateral mass of the muscle were used to estimate the myofibre cross-sectional area for both quadriceps of each subject.

2. The cross-sectional area of the quadriceps of each patient's injured limb was always smaller than that of the contralateral muscle. The wasting was largely localized to the quadriceps, with relative sparing of the other thigh muscles.

3. None of the biopsies showed any abnormality apart from a reduction in fibre size. In each case, the injured limb's reduced quadriceps cross-sectional area was associated with a reduced mean fibre area.

4. The ratio of the cross-sectional area of a muscle to its mean fibre area is a function of the number of fibres it contains. The ratio varied considerably from patient to patient but there was close agreement between the values obtained for the two limbs of each patient.

5. The quadriceps wasting produced by knee injury was due to muscle fibre atrophy. There was no evidence for a change in the number of fibres in the muscle.
Intravenous Infusion of α-Oxoisocaproate: Influence on Amino Acid and Nitrogen Metabolism in Patients with Liver Cirrhosis
Authors: Eriksson L. S. , Hagenfeldt L. , Wahren J.
Published: August 2015

1. The metabolic effect of α-oxoisocaproate (4-methyl-2-oxovalerate) infusion was examined in six patients with cirrhosis and in nine healthy control subjects. The arterial concentrations of amino acids, urea, ammonia, insulin and catecholamines were determined in the basal state and during intravenous infusion of α-oxoisocaproate (300 μmol/min) for 150 min. The exchanges of amino acids and substrates across the splanchnic region, the brain and the leg were examined in the healthy subjects by a catheter technique.

2. Basal α-oxoisocaproate levels were similar in patients and control subjects. During infusion the concentrations of α-oxoisocaproate rose to 90–130 μmol/l; they were 20–35% lower in the patients. Arterial leucine concentration increased in both groups to 250–300 μmol/l. Valine and isoleucine concentrations decreased (50–60%) as did to a lesser extent the concentrations of aromatic amino acids and methionine.

3. Regional exchange of amino acids was not significantly influenced by α-oxoisocaproate infusion. Arterial urea concentration decreased (12%, P < 0.05) and ammonia levels rose (15–25%, P < 0.05) in both groups. In the patients both adrenaline (100%, P < 0.001) and noradrenaline concentrations were elevated (350%, P < 0.001) in the basal state; insulin levels were similar to those in control subjects.

4. It is concluded that α-oxoisocaproate is rapidly transaminated to leucine in patients with cirrhosis and in healthy control subjects. α-Oxoisocaproate infusion resembles leucine infusion in its influence on aromatic amino acid concentrations, but in addition it elicits increased ammonia levels and decreased urea formation.
Indomethacin or Aprotinin Infusion: Effect on Reversal of Chronic Two-Kidney, One-Clip Hypertension in the Conscious Rat
Authors: Russell G. I. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. Blood pressure was monitored continuously in conscious rats with chronic Goldblatt two-kidney, one-clip hypertension.

2. Hypertension was rapidly reversed by removal of the constricting clip and the reversal was complete by 12 h, although structural vascular changes persisted for much longer.

3. Blood pressure in this model of hypertension was not affected by a 15 h infusion of either indomethacin or aprotinin.

4. The pattern of fall in blood pressure after removal of the clip was similar when animals were infused with either indomethacin or aprotinin. Blood pressure at 24 h was normal and did not differ significantly from that of unclipped rats given a glucose infusion.

5. The fall in blood pressure produced by unclipping therefore did not appear to be mediated via the prostaglandin or kallikrein systems.
Turnover Studies of Human β2-Microglobulin in the Rat: Evidence for a β2-Microglobulin-Binding Plasma Protein
Authors: Nguyen-Simonnet H. , Vincent C. , Gauthier C. , Revillard J. P. , Pellet M. V.
Published: August 2015

1. 123I-labelled β2-microglobulin (β2m) was injected into rats and protein or non protein-bound radioactivity was determined in plasma urine and several organs.

2. The observed kinetics differed from those expected according to the bicompartmental model for plasma protein turnover. The difference was attributed to the binding of a part of the tracer to a plasma component. Chromatography of plasma taken after injection of β2m showed an additional peak of radioactivity at the 55 000–80 000 daltons position.

3. In animals with ligated renal arteries, disappearance of the tracer from the plasma was markedly prolonged, and little non-protein-bound radioactivity was detectable in plasma, indicating that the kidney was the major site of catabolism of β2m.

4. Chromatography of plasma from control rats and rats with ligated renal arteries showed that the kidney was the major site of catabolism for free β2m only.

5. In normal rats, the urine was found to contain only non-protein-bound radioactivity.
Evidence for a Lactate Transporter in the Plasma Membrane of the Rat Hepatocyte
Authors: Monson J. P. , Smith J. A. , Cohen R. D. , Iles R. A.
Published: August 2015

1. The rate of uptake in 15 s of l- and d-lactate was studied in isolated hepatocyte preparations from starved rats.

2. Observations were also made of the effect of different concentrations of unlabelled l- and d-lactate on l-[14C]- and d-[14C]-lactate uptake.

3. Lactate uptake into hepatocytes appears to occur by two processes, one saturable and at least partially stereospecific, the other nonsaturable, at least up to 28 mmol/l, and probably representing simple non-carrier assisted diffusion.

4. The 15 s uptake of lactate is inhibited by α-cyano-3-hydroxycinnamate and by p-chloromercuriphenylsulphonate but not by the general anion transporter inhibitor 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonic acid, ouabain or the structural analogue dl-p-hydroxyphenyl-lactate.

5. Transporter-mediated lactate entry into liver cells is enhanced by lowered extracellular pH.

6. It is suggested that the contribution of the diffusion component of lactate entry into the cell may be exaggerated by the artifactual nature of the isolated hepatocyte preparation, and that, under some circumstances in vivo, lactate transport into hepatocytes could determine the rate of lactate removal from blood.
Sympathetic Reflex Control of Subcutaneous Blood Flow in Tetraplegic Man during Postural Changes
Authors: Skagen K. , Jensen K. , Henriksen O. , Knudsen L.
Published: August 2015

1. The effect of head-up tilt upon subcutaneous blood flow in the distal arm and leg was studied in 12 patients with complete traumatic spinal cord transection at the cervical level.

2. Blood flow was measured by the local 133Xe washout technique.

3. Leg lowering induced a 47% decrease in blood flow in the distal leg. During head-up tilt (45°) blood flow in the leg decreased by 48%. In the arm remaining at heart level blood flow decreased by 37% during tilt and this vasoconstriction could be prevented by nervous blockade with lignocaine injected subcutaneously 5 cm proximally to the labelled area. Leg blood flow was unaltered by proximal blockade but could be blocked by local infiltration in the labelled area with lignocaine in low doses.

4. Head-up tilt of tetraplegic patients induced vasoconstriction in the subcutaneous tissue of the forearm, which could be prevented by proximal blockade. Thus the vasoconstriction could be due to a spinal sympathetic reflex mechanism. This as well as local mechanisms including the veno-arteriolar reflex may play a role in recovery of arterial blood pressure during head-up tilt in the tetraplegic patient.
Uptake of l-valyl-l-Valine and Glycylsarcosine by Hamster Jejunum in Vitro
Authors: Burston D. , Wapnir R. A. , Taylor E. , Matthews D. M.
Published: August 2015

1. Preliminary observations concerned with the effect of the lipophilic properties of the amino acid side-chains of peptides on their apparent affinity for uptake by rings of everted hamster jejunum showed that of the series glycylglycine, l-alanyl-l-alanine, l-valyl-l-valine and l-leucyl-l-leucine, with increasingly lipophilic side-chains, l-valyl-l-valine, not l-leucyl-l-leucine, was the most powerful inhibitor of uptake of the hydrolysis-resistant dipeptide glycylsarcosine. This apparently anomalous observation indicated a need for further investigation, and this paper reports investigations of the kinetics of uptake of l-valyl-l-valine and of competition for uptake between l-valyl-l-valine and glycylsarcosine.

2. l-Valyl-l-valine was capable of complete competitive inhibition of mediated uptake of glycylsarcosine. Free l-valine did not inhibit mediated uptake of glycylsarcosine. Glycylsarcosine could inhibit mediated uptake of l-valyl-l-valine only partially, but a mixture of glycylsarcosine and l-valine was capable of producing complete inhibition of mediated uptake of l-valyl-l-valine.

3. Investigation of the kinetics of uptake of l-valyl-l-valine indicated two mediated components. Component (a), which disappeared in the presence of free l-leucine, probably represented uptake of free l-valine after hydrolysis of the peptide. Component (b) probably represented peptide uptake.

4. The estimates of Kt obtained for uptake of intact l-valyl-l-valine were many times greater than Ki for inhibition of uptake of glycylsarcosine by l-valyl-l-valine. A possible explanation of the discrepancy is the existence of two pathways for uptake of l-valyl-l-valine and glycylsarcosine, for one of which l-valyl-l-valine has a low Kt (i.e. a high affinity) not readily demonstrable by kinetic analysis.

5. The results suggest that mediated uptake of l-valyl-l-valine is the result of at least two processes, uptake of intact peptide by a mechanism or mechanisms shared with glycylsarcosine and also hydrolysis followed by uptake of free l-valine; estimates of the proportions of intact valine and of free valine taken up by mediated transport suggest that at pH 5 uptake of intact peptide varies from 25% at low concentrations to 55% at high concentrations. They do not explain why l-valyl-l-valine is a stronger inhibitor of uptake of glycylsarcosine than the more lipophilic l-leucyl-l-leucine, but do suggest how such a situation could arise.
Plasma Histamine and Catecholamines in Stable Asthmatic Subjects
Authors: Barnes P. J. , Ind P. W. , Brown M. J.
Published: August 2015

1. Venous plasma histamine and catecholamines were measured in stable asthmatic subjects by a recently developed specific and sensitive radioenzymatic assay.

2. Plasma histamine concentrations were significantly elevated in both extrinsic and intrinsic asthmatic subjects, compared with both normal controls and patients with chronic obstructive airways disease. There was no correlation between histamine concentration and severity of airways obstruction, however.

3. Elevated plasma histamine concentrations at rest-5-indicate increased release of mediators from ‘leaky’ mast cells in asthma.

4. Plasma catecholamine concentrations in asthmatic subjects did not differ from normal and there was no correlation with severity of broncho- constriction or with plasma histamine concentration.
Set-Point Displacement for Behavioural Thermoregulation in Anorexia Nervosa
Authors: Luck P. , Wakeling A.
Published: August 2015

1. The temperatures of thermal stimuli which evoked a feeling of maximal pleasantness upon contact with the hands of 14 malnourished patients with anorexia nervosa and 19 control subjects have been determined. A uniform skin temperature of 35°C for all individuals studied was achieved by immersion of the subjects and patients in water at that temperature. Core temperatures of the anorexic patients were similar to those of the control subjects, but six of the patients preferred temperatures that were significantly higher than those of the control subjects. The thermal preferences of the remainder of the patients were similar to those of the control subjects.

2. The abnormally high thermal preferences of some of the anorexic patients could not be attributed to abnormal thyroid status, since values for serum free thyroxine measured in this group were similar to those obtained for the remaining patients. The abnormal responses persisted after there had been a substantial gain in the patients'weight and did not therefore appear to be directly due to malnutrition.

3. Elevation of deep body temperature produced an expected shift in preference towards lower stimulus temperatures in a sample of subjects from the control group, and in the patients who had initially preferred temperatures within the range of the controls. In the patients who had initially preferred abnormally high stimulus temperatures, however, hyperthermia produced little change in thermal preference.

4. It is suggested that an elevation in the set-point temperature for behavioural thermoregulation can occur in some patients with anorexia nervosa, and that this displacement-5-contribute to the distressing sense of cold which some patients experience.
Propranolol Absorption in Untreated Coeliac Disease
Authors: Sandle G. I. , Ward A. , Rawlins M. D. , Record C. O.
Published: August 2015

1. To compare the bioavailability and the elimination of propranolol in seven untreated coeliac patients and six normal subjects, plasma concentrations were measured after oral and intravenous propranolol. The bioavailability and clearance of propranolol were similar in both groups.

2. With the use of a perfusion technique, propranolol absorption in the proximal jejunum was found to be decreased by 71% in five untreated coeliac patients, compared with the absorption in four normal subjects.

3. These results indicate that propranolol absorption is decreased in the proximal jejunum in untreated coeliac disease but overall absorption in the small bowel is not impaired.
The Effect of Dietary Sodium on the Blood Pressure Response to Dopamine Infusion in the Conscious Rat
Authors: Obika L. F. O. , Schneider E. G.
Published: August 2015

1. The influence of dietary sodium intake on the pressor response to intravenously infused dopamine in the conscious rat was studied.

2. Chronic sodium restriction significantly reduced the pressor response to infused dopamine, whereas high sodium diet enhanced the response.

3. Sodium intake is an important determinant of the pressor response to dopamine.
Determination of True Specific Activity of Superoxide Dismutase in Human Erythrocytes
Authors: Saito Takeshi , Ito Keizo , Kurasaki Masaaki , Fujimoto Shun , Kaji Hiroshi , Saito Kazuo
Published: August 2015

1. Activities, contents and true specific activities of superoxide dismutase (SOD) were determined in human erythrocytes of 105 normal healthy subjects.

2. The mean SOD activity assayed by the inhibition of xanthine autoxidation was 11·0 × 103 units/g of haemoglobin (Hb).

3. The mean SOD content assayed by an immunochemical method was 456 μg/g of Hb.

4. Both activity and content of SOD showed normal distributions, and no significant variations with regard to sex and age were detected.

5. A highly positive correlation between activities and contents of SOD was observed in normal healthy subjects (r = 0·77, P < 0·001).

6. True specific activity was calculated from levels of activity and content of SOD. The mean true specific activity of SOD in human erythrocytes was 23·7 units/μg of SOD.

7. There was no significant difference in true specific activity between young and old subjects.
Assessment of Intestinal Permeability in the Experimental Rat with [3H]Cellobiotol and [14C]Mannitol
Authors: Sandhu J. S. , Fraser D. R.
Published: August 2015

1. The intestinal absorption of a mixture of [3H]cellobiotol and [14C]mannitol was determined by measuring the 3H/14C ratio in urine after oral administration of the labelled sugars to rats. This index of intestinal permeability was used to identify cellular dysfunction in experimental enteropathy in rats.

2. Rats with mucosal damage induced with ethanol showed an increased uptake of [3H]cellobiotol and a decreased uptake of [14C]mannitol compared with normal controls. The increased 3H/14C ratio in urine reflected the abnormal cell function known to be caused by ethanol.

3. Methotrexate treatment reduced the absorption of the two sugars whereas cetrimide treatment enhanced their absorption. However, in both methotrexate-induced and cetrimide-induced enteropathy the 3H/14C ratio in urine was unaffected by the mucosal damage. Here the permeability change was not related to absorptive dysfunction of the mucosal cells.

4. It is concluded that this labelled sugar absorption test enables the rapid and accurate identification of malfunction of intestinal mucosal cells in the rat. Moreover, the test distinguishes between changes in permeability caused by abnormal cell function and changes caused by gross disturbance of the structure of the mucosal surface.
The Response of Plasma Immunoreactive Adrenocorticotropin, β-Endorphin/β-Lipotropin, γ-Lipotropin and Cortisol to Experimentally Induced Pain in Normal Subjects
Authors: Güllner Hans-Georg , Nicholson Wendell E. , Wilson Margaret G. , Bartter Frederic C. , Orth David N.
Published: August 2015

1. We examined the effect of ischaemic pain and sustained isometric muscle contraction on plasma immunoreactive γ-lipotropin (γLPH), β-endorphin/β-lipotropin (βEND/βLPH) and corticotropin (ACTH), which are all synthesized from a common precursor (pro-opiocortin), and plasma Cortisol in 10 normal subjects.

2. Experimental pain was produced by inflation to 250 mmHg of a sphygmomanometer cuff, placed above the elbow of the ‘dominant’ arm, after which the subject squeezed a hand dynamometer, loaded to 12 kg, 20 times at 2 s intervals. Blood was drawn before, after 5 and 10 min of pain, and 30 min after release of the cuff. In a control session, the subjects were asked to squeeze the handgrip alone for 5 min at 30% of their maximum strength, a procedure which elevates the blood pressure without causing pain.

3. One subject had unexplained high (30–71 pmol/l) baseline peptide concentrations. Baseline values for the nine other subjects were: ACTH, 7·3 ± 1·9 pmol/l (mean ± sem); γLPH, 18·6 ± 1·0 pmol/l; βEND/βLPH, 10·0 ±1·1 pmol/l; Cortisol, 599 ±55 nmol/l. Neither procedure significantly increased the plasma concentration of ACTH or any other peptide, whereas plasma Cortisol was significantly increased at both 5 min and 10 min. Plasma ACTH was positively correlated with plasma γLPH (r = 0·701; P < 0·001), βEND/βLPH (r = 0·970; P < 0·001) and plasma Cortisol (r = 0·758; P < 0·05).

4. The present study demonstrates that, in normal man, plasma endorphins do not change with experimental ischaemic pain. The rise in plasma Cortisol without concomitant rise in ACTH is not explained, but suggests the action of some other agent at the level of the adrenal cortex.
Intracellular Na+ and Ca2+ Activities in Essential Hypertension
Authors: Zidek W. , Vetter H. , Dorst K.-G. , Zumkley H. , Losse H.
Published: August 2015

1. The intracellular Na+ and Ca2+ activity and Na+ concentration were measured in erythrocytes of normotensive subjects, with and without a familial disposition to hypertension, in essential hypertensive patients with and without a family history of hypertension, and in patients with secondary hypertension.

2. In normotensive subjects without a genetic trait of hypertension intracellular Na+ activity and concentration were 7.00 ± 1.38 mmol/l and 5.67 ± 0.95 mmol/l respectively. The intracellular Ca2+ activity was 4.82 ± 4.49 μmol/l. In normotensive subjects with a familial hypertensive disposition intracellular Na+ activity and concentration were 9.74 ± 1.43 mmol/l (P < 0.01) and 6.63 ± 0.88 mmol/l (P < 0.05). Intracellular Ca2+ was 9.59 ± 9.71 μmol/l (P < 0.05).

3. Essential hypertensive patients without a familial genetic trait had an elevated intracellular Na+ activity (8.35 ± 2.08 mmol/l, P < 0.05). Intracellular Na+ concentration was 6.64 ± 0.79 mmol/l (P < 0.05). The intracellular Ca2+ activity was markedly elevated to 25.33 ± 19.03 μmol/l (P < 0.01). The essential hypertensive patients with a familial disposition had an elevated intracellular Na+ activity (17.19 ± 4.37 mmol/l, P < 0.001) and Ca2+ activity (32.8 ± 32.51 μmol/l, P < 0.01). The intracellular Na+ concentration was 6.25 ± 1.23 mmol/l.

4. The results indicate that in essential hypertension intracellular Na+ activity is increased, particularly in patients with a familial disposition for hypertension. Intracellular Ca2+ is increased in essential hypertension whether or not there was a family disposition to hypertension.
Measurements of Myofibrillar Protein Breakdown in Newborn Human Infants
Authors: Burgoyne J. L. , Ballard F. J. , Tomas F. M. , Dobozy A. , MacLennan A. H. , Fitzgerald A. , Dahlenburg G. W.
Published: August 2015

1. Myofibrillar protein breakdown was calculated from the urinary excretion ratio of Nτ-methylhistidine (3-methylhistidine) to creatinine in newborn premature and full-term infants. Representative values were obtained from single voidings provided that the infant's metabolic status was stable.

2. Nτ-Methylhistidine in infant urine was measured by a rapid Auto Analyser method and shown to give similar values to those obtained by ion-exchange separation techniques.

3. The molar excretion ratio of Nτ-methylhistidine to creatinine averaged 0·0159 in urine samples obtained within 12 h after birth. A similar ratio was found in amniotic fluid collected at birth. It is argued that this ratio does not reflect a low rate of myofibrillar protein breakdown in the foetus, but rather a more effective transplacental passage of Nτ-methylhistidine than of creatinine.

4. The urinary ratio increased during the first 2 days after birth to a plateau at 0·0372. This represents a myofibrillar protein degradation rate of 3·40% day−1 in full-term infants.

5. The molar excretion ratio during the period 40–120 h after birth increased in premature infants and reflects a fractional degradation rate of 5·34% day−1 in those infants weighing less than 1 kg at birth.

6. Lower excretion ratios were found in some infants of diabetic mothers and in athyroid infants.

7. The urinary excretion ratio of Nτ-methylhistidine to creatinine is presented as a useful method for evaluating the breakdown rate of myofibrillar protein in neonates and can be applied to a number of abnormal nutritional or hormonal states.
The Effects of Localized Hypoventilation on Ventilation/Perfusion Ratios and Gas Exchange in the Dog Lung
Authors: Suggett A. J. , Barer Gwenda R. , Mohammed F. H. , Gill G. W.
Published: August 2015

1. Hypoventilation of one lobe of lung was studied in open-chest anaesthetized dogs. Lobar blood flow, pulmonary-artery pressure and gas exchange were measured, the latter from breath-by-breath analysis with a mass spectrometer.

2. Hypoventilation of the lobe by reducing the respiratory pump stroke led, at each step, to a reduction in blood flow to that lobe. The flow () reduction was variable, but always less than the ventilation () reduction, so that the ratio to the lobe was reduced. O2 tension and pH fell and CO2 tension rose in effluent blood. Thus regulation achieved by flow reduction varied between individuals and was of low gain.

3. Anatomical or series dead space (VD series) was reduced in proportion to ventilation. When VD series was less than the apparatus dead space, some gas exchange still took place.

4. Oxygen uptake () and CO2 output () were reduced during hypoventilation. fell more than , so that the respiratory exchange ratio (R) was reduced.

5. Whether the deterioration in gas tensions in effluent blood during hypoventilation of the lobe was due to shunt of blood past unventilated alveoli, or to mismatching, was not resolved.

6. The plateau phase of the CO2-output curves at low tidal volumes was usually regular; thus either hypoventilation was uniform, or some ventilation units were totally closed.
The Effects on Respiration in the Cat of the Sudden Excitation of Cerebral Vascular Nociceptors by Carbon Dioxide
Authors: Hanson M. A. , Nye P. C. G. , Torrance R. W.
Published: August 2015

1. Injection of CO2-saturated saline in a distal direction into either a vertebral artery or an internal maxillary artery in pentobarbitone-anaesthetized cats produced abrupt changes in respiration. Vertebral-artery injections produced a transient inhibition of respiration, followed by a stimulation of it. Internal-maxillary-artery injections produced only the inhibition.

2. Injections during inspiration usually shortened that inspiration, reduced its volume and prolonged the following expiration. In the first 30% of an expiration they prolonged that expiration, but given in the next 50% they shortened it. In the last 20% of expiration internal-maxillary-artery injections again slightly prolonged the expiration.

3. Phenyl diguanide injected into either a vertebral or an internal maxillary artery also produced abrupt effects on respiration.

4. The effects of CO2-saturated saline were abolished by intravenous acetazolamide, suggesting that nociceptors may be affected by a change in local pH.

5. The effects may arise from the excitation of vascular nociceptors, and our observations may suggest a way of studying in animals the receptors responsible for headache.
The Antidiuretic Effect of Chronic Hydrochlorothiazide Treatment in Rats with Diabetes Insipidus: Water and Electrolyte Balance
Authors: Walter S. J. , Skinner J. , Laycock J. F. , Shirley D. G.
Published: August 2015

1. The antidiuretic effect of hydrochlorothiazide in diabetes insipidus was investigated in rats with the hereditary hypothalamic form of the disease (Brattleboro rats).

2. Administration of hydrochlorothiazide in the food resulted in a marked fall in urine volume and a corresponding rise in osmolality. These effects persisted throughout the period of treatment (6–7 days).

3. Body weight and extracellular volume were significantly reduced in the thiazide-treated rats.

4. Hydrochlorothiazide caused an increase in urinary sodium excretion only on the first day of treatment. The resulting small negative sodium balance (in comparison with untreated rats) remained statistically significant for 2 days only. Thiazide-treated rats gradually developed a potassium deficit which was statistically significant from the fourth day of treatment.

5. Total exchangeable sodium, measured after 7 days of thiazide treatment, was not significantly different from that of untreated rats. However, plasma sodium was reduced in thiazide-treated animals, whereas erythrocyte sodium concentration was elevated.

6. It is concluded that the antidiuresis resulting from chronic hydrochlorothiazide administration is associated with a reduction in extracellular volume, but not with a significant overall sodium deficit. Hydrochlorothiazide appears to cause a redistribution of the body's sodium such that the amount of sodium in the extracellular fluid compartment is reduced.
Calcium-Induced Contraction and Effect of Calcium Antagonist on Arterial Smooth Muscle of Spontaneously Hypertensive Rats
Authors: Kawaguchi Yoshinori , Aoki Kyuzo , Yamamoto Masahiko , Hotta Ken
Published: August 2015

1. Calcium reactivity of arterial smooth muscle and the effect of diltiazem (calcium antagonist) were investigated in helical strips of mesenteric arteries from 6-week-old male spontaneously hypertensive rats (SHR) and age-and sex-matched normotensive Wistar-Kyoto (WKY) rats. Blood pressure was 130 ± 5 mmHg for SHR and 110 ± 5 mmHg for WKY rats (means ± sd).

2. At high Ca2+ concentration (3 × 10−4 to 3 × 10−3 mol/l) the calcium-induced tension of mesenteric arterial strips per cross-sectional area was significantly greater in SHR than in WKY rats in noradrenaline (10−5 mol/l)-containing solution or in high K+ (121 mmol/l) solution (P < 0.001). At low Ca2+ concentration (10−5 mol of noradrenaline/l and 3 × 10−5 mol/l in high K+), the tension was smaller in SHR strips than in WKY rat strips (P < 0.05).

3. The Ca2+ sensitivity of SHR strips was significantly lower than that of WKY strips in noradrenaline-containing solution or in high K+ solution.

4. Diltiazem, a calcium antagonist, shifted the dose-response curve of Ca2+-induced tension to the right equally in SHR and WKY rat strips. The inhibition of the maximum tension by the drug was greater in SHR strips than in WKY rat strips in noradrenaline-containing solution, but there was no difference in high K+ solution.

5. The results suggest that the contractile abnormality might be a possible cause of hypertension in SHR.
Biological Activity of Angiotensin II-(4-8)-Pentapeptide in Man
Authors: Kono T. , Oseko F. , Ikeda F. , Imura H. , Khosla M. C. , Bumpus F. M.
Published: August 2015

1. When the angiotensin II-(4-8)-pentapeptide was infused intravenously at rates of 0.31-5.55 nmol min−1 kg−1 for 10–120 min into five normal men or two patients with Bartter's syndrome, no significant change was observed in blood pressure, plasma renin activity and plasma aldosterone, and the lowest dose did not inhibit the captopril-induced increase in plasma renin activity in the normal men.

2. An intravenous infusion of the pentapeptide at 9–0 nmol min−1 kg−1 for 15 min significantly raised blood pressure in the five normal men but not in patients with Bartter's syndrome. Blood pressure returned to the pre-treatment level 60 min after the cessation of the infusion in the normal men.

3. At the same dose level none of the seven subjects examined showed any significant change in plasma renin activity and plasma aldosterone.

4. Angiotensin II-(5-8)-tetrapeptide was infused intravenously into one of the normal men at a rate of 41.5 nmol min−1 kg−1 for 15 min, but it caused no significant change in blood pressure, plasma renin activity and plasma aldosterone.

5. These results suggest that the pentapeptide and probably the tetrapeptide do not possess renin-suppressing and steroidogenic actions in man but that the former peptide does elicit a modest pressor action with a prolonged duration.
Inactivation of Bradykinin and Angiotensin I Conversion in Conscious Rats with Two-Kidney, One-Clip Hypertension
Authors: Trindade Inge E. K. , Krieger Eduardo M.
Published: August 2015

1. The extents of pulmonary degradation of bradykinin (BK) and angiotensin I (ANG I) to angiotensin II (ANG II) conversion were measured simultaneously to determine whether converting enzyme activity, in vivo, is altered in two-kidney, one-clip hypertensive rats (15, 60 and 180 days after renal artery clipping).

2. Inactivation of BK (estimated by comparing equipressor doses injected intravenously and intra-aortically) was markedly increased in these hypertensive rats: 98.5% (15 days), 98.4% (60 days) and 99.5% (180 days) vs 95.6% in control rats. All groups of hypertensive rats exhibited hyper-reactivity to intra-aortic BK, requiring doses 14–38 times smaller than the control rats to produce the same depressor response.

3. The percentage of ANG I conversion (calculated from equipressor doses of ANG I and ANG II injected intravenously) was elevated after 15 days (46.0% vs 28.1% in control rats), unchanged after 60 days (27.7%) and slightly elevated after 180 days (36.0%). Hyporeactivity to ANG II was observed 15 and 180 days after renal artery clipping (doses six times were needed to produce a standard increase in mean arterial pressure). No alterations were found in the rats at 60 days after artery clipping.

4. The increased degradation of BK cannot be explained solely by elevation of converting enzyme activity since no parallel increase in ANG I conversion was observed, indicating that other bradykininases in the lung may be involved.
Radiotracer Methodology for the Simultaneous Estimation of Total, and Renal, Sympathetic Nervous System Activity in Humans
Authors: Esler Murray , Blombery Peter , Leonard Paul , Jennings Garry , Korner Paul
Published: August 2015

1. A radiotracer method, based on the measurement of noradrenaline spillover to plasma, has been developed to estimate simultaneously total, and organ-specific, sympathetic nervous system tone in humans.

2. Total, and renal, noradrenaline spillover to plasma was measured in four patients with essential hypertension. Renal noradrenaline spillover was 0.42 ± 0.25 nmol/min (mean ± sd), constituting approximately 16% of total noradrenaline spillover (2.58 ± 0.20 nmol/min).

3. There is a need to study regional sympathetic nervous tone, of organs particularly involved in blood pressure regulation, in patients with essential hypertension. Local increases in sympathetic tone might not be detected by biochemical tests of overall sympathetic nervous system activity.