bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Arterial Blood Pressure, Plasma Renin Activity and Plasma Aldosterone Concentration to Long-Term Administration of Captopril in Patients with Severe, Treatment-Resistant Malignant Hypertension
Authors: McCaa Connie S. , Langford H.G. , Cushman W. C. , McCaa R. E.
Published: August 2015

1. The response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to inhibition of angiotensin I converting enzyme (kininase II) with captopril has been studied in patients with severe, treatment-resistant, malignant hypertension.

2. Nine patients with a past history of severe hypertension, supine diastolic blood pressure > 120 mmHg before conventional antihypertensive therapy and resistant to conventional antihypertensive therapy were studied.

3. Captopril administration resulted in a marked decrease in arterial blood pressure and plasma aldosterone concentration and an increase in plasma renin activity.

4. Although arterial blood pressure remained significantly below the values observed during the control period, pressure did tend to increase again after 3 days. Addition of hydrochlorothiazide kept arterial pressure significantly below pretreatment control values.
The Effects of Metoprolol on Ambulatory Blood Pressure
Authors: Mann S. , Craig M. W. Millar , Altman D. G. , Melville D. I. , Raftery E. B.
Published: August 2015

1. Continuous monitoring of arterial pressure was performed via an indwelling cannula over 24 h in 12 hypertensive patients before treatment and again 2–4 months after starting metoprolol (100 mg twice daily).

2. During treatment, heart rate and systolic and diastolic pressures were significantly reduced.

3. The circadian patterns of heart rate and blood pressure changes were similar before and during therapy.
Comparative β-Adrenoreceptor-Blocking Effects and Pharmacokinetics of Propranolol and Pindolol in Hypertensive Africans
Authors: Salako L. A. , Falase A. O. , Aderounmu A. Fadeke
Published: August 2015

1. The β-adrenoreceptor-blocking effects of pindolol were compared with those of propranolol and a placebo in a double-blind cross-over trial involving nine hypertensive African patients.

2. Heart rate, systolic blood pressure and diastolic blood pressure were measured at rest and immediately after exercise before and at intervals up to 6 h after oral administration of the drugs. In addition, plasma pindolol and propranolol concentrations were determined at the same intervals.

3. Pindolol diminished systolic blood pressure at rest and after exercise and antagonized exercise-induced tachycardia, but had no effect on resting heart rate. Propranolol diminished systolic blood pressure predominantly after exercise and reduced both resting and exercise heart rate. Both drugs had no effect on diastolic pressure.

4. The mean plasma concentration reached a peak at 2 h for each drug and this coincided with the interval at which maximal β-adrenoreceptor-blocking effect was observed.
Effect of Increasing Doses of Labetalol on Blood Pressure, Plasma Renin Activity and Aldosterone in Hypertensive Patients
Authors: Salvetti A. , Pedrinelli R. , Sassano P. , Arzilli F.
Published: August 2015

1. Four different doses of labetalol (150, 300, 600 and 900 mg/day) were given for 1 week to each of four groups of patients with essential hypertension (six patients for each group).

2. Labetalol decreased mean blood pressure and heart rate to the same extent on the first and the seventh days of treatment. Only standing blood pressure showed a dose-dependent decrement, and heart rate showed a dose-dependent inhibition both in the supine and upright position.

3. Labetalol exerted a net inhibitory effect on plasma renin activity, which was related to basal renin values and was already maximal at the lowest doses. This effect was well maintained in the supine position, although during standing it tended to be less evident with increasing doses.

4. Urinary aldosterone was decreased in a dose-dependent fashion and its changes were largely independent of plasma renin activity.

5. Neither basal values nor changes of renin and aldosterone were related to the hypotensive effect of labetalol.

6. During labetalol treatment urinary sodium excretion fell for 2–3 days and then returned to basal values. The retentive effect of labetalol on sodium was directly related to the decrease of blood pressure, and the successive sodium escape might be explained either by the observed increase of plasma volume (indirectly measured by packed cell volume) or by aldosterone inhibition.
Effect of Captopril on Renal Vascular Tone in Patients with Essential Hypertension
Authors: Mimran A. , Brunner H. R. , Turini G. A. , Waeber B. , Brunner D.
Published: August 2015

1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1).

2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min.

3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred.

4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively).

5. The logarithm of baseline plasma renin activity was positively correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance.

6. The results indicate that in patients with essential hypertension angiotensin participates actvely in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined.
Modulation of the Baroreceptor Reflex by Angiotensin II and other Vasoactive Drugs in Anaesthetized Greyhounds
Authors: Marker J. D. , Miles T. S. , Scroop G. C.
Published: August 2015

1. The effects of vascular infusions of acetylcholine, angiotensin II, noradrenaline and prostaglandin F2α on the baroreceptor reflex were studied in the anaesthetized greyhound.

2. Vertebral artery infusions of low doses of angiotensin II, but not of acetylcholine or prostaglandin F2α, resulted in a significant reduction in the depressor response to carotid sinus nerve stimulation.

3. The increases in blood pressure and heart rate in response to bilateral carotid artery occlusion were not significantly changed during vertebral artery infusions of acetylcholine, angiotensin II or prostaglandin F2α.

4. The increases in blood pressure in response to intravenous infusions of noradrenaline were significantly enhanced during vertebral artery infusions of acetylcholine and angiotensin II, but not of prostaglandin F2α. The bradycardia during noradrenaline infusions was significantly enhanced by angiotensin II alone.

5. The depressor response to carotid sinus nerve stimulation was significantly reduced during intravenous infusions of both noradrenaline and angiotensin II.

6. It is considered that although angiotensin II can be shown to have a specific central action to attenuate the response to carotid sinus nerve stimulation, the role of this action in the complete baroreceptor reflex is unproven.
Response of Chronic Renovascular Hypertension to Surgical Correction or Prolonged Blockade of the Renin–Angiotensin System by Two Inhibitors in the Rat
Authors: Thurston H. , Bing R. F. , Marks E. S. , Swales J. D.
Published: August 2015

1. Removal of the renal artery constriction but not of the clipped kidney restored the blood pressure to normal levels in Goldblatt two-kidney rats with hypertension of more than 4 months' duration.

2. Despite the differences in blood pressure response, both surgical procedures lowered plasma renin concentration to normal or below normal values.

3. Administration of the oral converting enzyme inhibitor SQ 14 225 produced a marked fall in blood pressure in Goldblatt kidney rats with chronic hypertension. However, a prolonged infusion of the angiotensin II antagonist saralasin was quite ineffective. The difference in response to the two inhibitors may have been due to bradykinin potentiation by the converting enzyme inhibitor.

4. Although plasma renin is often elevated in Goldblatt two-kidney rats with hypertension of more than 4 months' duration, the renin-angiotensin system plays no role in the maintenance of blood pressure at this stage.
The Effect of Mineralocorticoid Administration on Urine Free Dopamine in Man
Authors: Oates N. S. , Perkins C. M. , Lee M. R.
Published: August 2015

1. Five normal subjects were studied under metabolic conditions on a controlled sodium and potassium intake.

2. Plasma and urine free dopamine concentrations were measured in these subjects before, during and after 5 days administration of fludrocortisone (0·2 mg twice daily).

3. Urine free dopamine showed a tendency to fall during the early phase of fludrocortisone administration and then rose towards normal.

4. In a patient with primary hyperaldosteronism there was no evidence of increased renal production of dopamine. Urine dopamine fell when plasma renin activity rose as a result of spironolactone administration (200 mg three times a day for 5 days).

5. If renal dopamine has a role in mineralocorticoid ‘escape’ then it may be permissive only. The mechanisms of control of dopamine production could include tubular sodium concentration, tubular chloride concentration and intrarenal renin activity.
An Evaluation of the Clinical Potential of a Comprehensive Model of Human Respiration in Artificially Ventilated Patients
Authors: Hinds C. J. , Ingram D. , Adams L. , Cole P. V. , Dickinson C. J. , Kay J. , Krapez J. R. , Williams J.
Published: August 2015

1. We have investigated the feasibility of accurately simulating the respiratory function of artificially ventilated patients, using a computer model of the respiratory system. Twelve patients artificially ventilated after uncomplicated cardiac bypass surgery were studied.

2. The basic information required to simulate individual ventilated subjects was measured or derived. A program was written to enable key model parameters to be adjusted automatically to match model predictions to these clinical measurements. On completion of this matching procedure all the variables computed by the model were compared with patient values (measured or derived) and their accuracy was assessed.

3. The matching algorithm successfully optimized parameters of the model representing metabolic activity, tissue respiratory quotient, venous admixture, physiological dead space and total body bicarbonate to match measured values for oxygen consumption, carbon dioxide production, Pa,o2, Pa, co2 and arterial HCO−3 respectively. Other variables compared arise from the solution of equations within the model and correlation between model and patient values is generally good (r > 0·9). However, values of PV̇,o2 correlate less well (r = 0·85). Factors affecting the accuracy of patient simulation are discussed and some deficiencies analysed.

4. The creation of an accurate, steady-state representation of a patient by the model opens up the possibility of using it interactively as an aid to clinical management. Some possible future developments of the technique are discussed.
Equilibration of Tracer Radioiron with Body Iron
Authors: Charlton R. W. , Fatti L. P. , Lynch S. R. , Torrance J. D. , Bothwell T. H.
Published: August 2015

1. The degree to which a tracer quantity of 55Fe bound to transferrin and introduced into the plasma 36 months previously had equilibrated with the body iron was studied in a subject who was phlebotomized repeatedly until iron-deficiency anaemia developed.

2. Analysis of the results with two mathematical models showed that equilibration with haemoglobin iron and storage iron was complete.

3. Estimates of the quantity of iron initially stored in the body by three different methods yielded values of 37·3, 33·1 and 34·8 mmol.

4. Since the previously determined mean initial plasma ferritin concentration was 185 μg/l (462 pmol/l), there was 0·179–0·197 mmol of stored iron per 1 μg of plasma ferritin/l.

5. The study suggests that the assumption on which currently accepted values for daily body iron loss were calculated is valid.
Acid—Base Changes after Cardiorespiratory Arrest in the Dog
Authors: Greenwood P. V. , Rossall R. E. , Kappagoda C. T.
Published: August 2015

1. To assess the non-respiratory acid—base disturbance which results from cardiorespiratory arrest experiments were performed on anaesthetized dogs, and circulatory arrest was established either by inducing ventricular fibrillation or by complete occlusion of the great veins.

2. In the first series of experiments (group A) the period of cardiorespiratory arrest was limited to 2·0–3·5 min. It was shown that the non-respiratory component of the ensuing acid—base disturbance as expressed by the non-respiratory pH was small: in nine episodes of circulatory arrest after occlusion of the great veins there was a mean reduction in the non-respiratory pH of 0·04 pH unit (range 0·025–0·055), and in seven episodes of ventricular fibrillation the mean reduction was 0·024 pH unit (range 0–0·055).

3. In the second series of experiments (group B) the period of cardiorespiratory arrest was varied from 3·0 to 11·0 min. It was found that the degree of non-respiratory acidaemia was correlated with the duration of arrest but the magnitude of these changes was not large.
Lack of Effect of Somatostatin on Iodothyronine Release from the Perfused Canine Thyroid
Authors: Laurberg P.
Published: August 2015

1. This study has evaluated the effect of somatostatin (0.1 or 3 μg/ml) on the release of thyroxine, 3,5,3′-tri-iodothyronine and 3,3′,5′-tri-iodothyronine from perfused thyroid lobes.

2. Somatostatin did not affect either the total release of iodothyronines or the ratio between various iodothyronines in thyroid effluent from unstimulated and thyrotrophic hormone stimulated thyroid lobes.

3. The results lend no support to the idea that somatostatin present in the parafollicular cells of the thyroid should have regulatory function on thyroidal secretion of iodothyronines.
Cyclic Nucleotide Excretion in Human Malignancies
Authors: Hunt N. H. , Smith B. , Pembrey R.
Published: August 2015

1. Urinary cyclic nucleotide excretion was studied in 51 patients with malignant tumours and in 24 control subjects.

2. Adenosine 3′:5′-cyclic monophosphate excretion was normal in patients with tumours.

3. Urinary excretion of guanosine 3′:5′-cyclic monophosphate was significantly greater than normal in patients with lymphoid tumours (both sexes) and in male patients with myeloid tumours or malignant melanoma.

4. Guanosine 3′:5′-cyclic monophosphate excretion was normal in patients with breast carcinoma or colonic adenocarcinoma.
The Metabolism of a Physiological Dose of Radioactive Cholecalciferol (vitamin D3) to its Hydroxylated Metabolites in Man
Authors: Stanbury S. W. , Mawer E. Barbara
Published: August 2015

1. The metabolism of an intravenous pulse-dose of 65 nmol (25 μg) of double-isotope-labelled cholecalciferol has been studied in 28 individuals. The subjects comprised 19 with serum concentrations of 25–hydroxycalciferol (25–(OH)D) ≤ 25 nmol/l, of whom 12 had clinical osteomalacia, and nine with serum 25–(OH)D > 25 nmol/l (30–125 nmol/l).

2. The concentrations in serum of radioactive cholecalciferol, 25–hydroxycholecalciferol (25–(OH)D3) and the three dihydroxylated metabolites: 1,25–, 24,25– and 25,26–dihydroxycholecalciferol (1,25–(OH)2D3, 24,25-(OH)2D3 and 25,26–(OH)2D3) were measured for up to 10 days after the injection.

3. The temporal relationships between the formation of individual radioactive metabolites and factors apparently influencing their production are described and their molar concentrations in serum calculated.

4. Formation of radioactive 1,25-(OH)2D3 was detectable only in vitamin D—deficient subjects. Between individuals, its maximum serum concentration was correlated significantly and inversely with serum calcium but with no other measured variable. In the individual, concentrations of radioactive serum 1,25-(OH)2D3 varied directly with radioactive serum 25-(OH)D3.

5. The failure to detect formation of radioactive 1,25–(OH)2D3 in vitamin D—replete subjects suggests that current estimates of the daily turnover of the hormone in the normal individual may be severalfold too high.

6. Radioactive 25,26–(OH)2D3 was produced rapidly by all subjects and in greater amounts by vitamin D—deficient individuals. Between subjects and in the individual its concentration in serum correlated only with the radioactive serum 25–(OH)D3. Production of this metabolite appeared to be unregulated and dependent solely on the concentration of its precursor.

7. In vitamin D—replete subjects, production of 24,25–(OH)2D3 was also apparently determined by precursor concentration. In vitamin D—depleted subjects, production of radioactive 24,25–(OH)2D3 was variably delayed for up to or more than 10 days.

8. There appeared to be a constraint on the quantitative hepatic production of 25–(OH)D which is not explained by simple feed—back inhibition.

9. If sterols other than 1,25–(OH)2D3 are required to initiate the mineralization of osteomalacic bone, after correction of vitamin D deficiency in man, 25–(OH)D3 and 25,26–(OH)2D3 are produced sufficiently rapidly to meet this hypothetical requirement, but not 24,25–(OH)2D3.
The Effects of the Antagonists of the Renin—Angiotensin System on Cardiovascular Response to Lower-Body Subatmospheric Pressure in the Anaesthetized Cat
Authors: Adigun S. A. , Clough D. P. , Conway J. , Hatton R.
Published: August 2015

1. Lower-body subatmospheric (negative) pressure led to a prompt reduction in central venous pressure and arterial blood pressure. Arterial blood pressure was then restored within 30 s and there was a tachycardia. These reflex responses have been used to investigate the role angiotensin plays in blood pressure control.

2. The initial plasma renin activity (2.9 ng of angiotensin I h−1 ml−1) did not change during the brief lowering of pressure. Before pressure was lowered neither the angiotensin-converting enzyme inhibitor nor a competitive antagonist, [Sar1,Ala8]-angiotensin II, lowered arterial pressure.

3. Nevertheless, after inhibition of the renin-angiotensin system by these agents, the reduction in blood pressure induced by lower-body negative pressure became greater and the blood pressure recovery was impaired.

4. The findings suggest that angiotensin, at a blood concentration which has no direct effect on blood pressure, interacts with the sympathetic nervous system to maintain arterial blood pressure.
Cholesterol and Bile Acid Metabolism in Obesity
Authors: Leijd Barbro
Published: August 2015

1. The present study was undertaken to determine the influence of obesity on bile acid kinetics and cholesterol balance in man.

2. Fourteen obese and normolipidaemic patients (160 ± 6% of ideal body weight, mean ± sem) were studied under standardized dietary conditions. Bile acid kinetics were determined with the aid of 14C-labelled cholic acid and chenodeoxycholic acid. Cholesterol balance was calculated as the sum of bile acid synthesis plus daily faecal excretion of neutral C27 steroids minus dietary intake of cholesterol. The results obtained were compared with previously published data on control subjects (n = 13).

3. The cholesterol balance was higher in the obese patients (2.61 ± 0.27 mmol/day) than in the control subjects (1.78 ± 0.22 mmol/day), owing to a higher excretion of neutral steroids. When expressed per kg of body weight the cholesterol balance was quite normal in the obese patients.
The Removal of Infused Leucine after Injury, Starvation and other Conditions in Man
Authors: Elia M. , Farrell Rose , Ilic Vera , Smith R. , Williamson D. H.
Published: August 2015

1. To investigate the effects of starvation, elective surgery, accidental injury and other clinical conditions on the metabolism of branched-chain amino acids in man, we have measured the basal concentration of leucine and the removal and metabolic effects of infused l-leucine.

2. The blood concentration of leucine was significantly increased by surgery, starvation and accidental injury, and decreased in cirrhosis. It tended to increase in diabetes and was unaffected by muscular dystrophy.

3. The half-life of infused leucine was nearly doubled by 4 days of complete starvation, unaltered by surgery and decreased by severe accidental injury. Infusion with Intralipid, which increased free fatty acid and ketone-body concentrations, had no effect on the removal of a leucine load. The clearance rate of infused leucine was reduced in diabetes and muscular dystrophy and increased in cirrhosis.

4. The effects of infused leucine on blood glucose and ketone bodies differed according to the groups studied.

5. Since the traumatized patients were given sufficient energy and nitrogen and disposed of a leucine load at a different rate from the starved patients, the causes of the increase in blood concentration of leucine in these two conditions are different.
Plasma High-Density Lipoprotein Metabolism in Subjects with Primary Hypertriglyceridaemia: Altered Metabolism of Apoproteins AI and AII
Authors: Rao S. N. , Magill P. J. , Miller N. E. , Lewis B.
Published: August 2015

1. The metabolism of the major proteins of plasma high-density lipoprotein (HDL), apoproteins AI and AII, have been studied in 10 normotriglyceridaemic subjects and in 11 hypertriglyceridaemic subjects (plasma triglyceride 4.5–25 mmol/l) by kinetic analysis of the plasma specific radioactivity versus time curves of the apoproteins after intravenous injection of autologous 125I-labelled high-density lipoprotein.

2. The specific radioactivity versus time curves of both apoproteins (followed for 14 days) were bi-exponential in all subjects.

3. The plasma apoprotein AI and AII concentrations were significantly lower in the hypertriglyceridaemic subjects than in the normotriglyceridaemic subjects. Kinetic analysis showed that this was associated with a lower rate of synthesis of apoprotein AI (P < 0.01) and a higher fractional catabolic rate of apoprotein AII (P < 0.01) in the hypertriglyceridaemic group.

4. There were no significant differences between the two groups in the synthetic rate of apoprotein AII, the fractional catabolic rate of apoprotein AI or the intravascular/extravascular distributions of the apoproteins.

5. Thus hypertriglyceridaemia appears to be frequently associated with divergent abnormalities of the metabolism of the major high-density lipoprotein apoproteins.
Rectal Mucosal Histamine Release in Ulcerative Colitis
Authors: Rampton D. S. , Murdoch R. D. , Sladen G. E.
Published: August 2015

1. Rectal dialysis in vivo was used to assess rectal mucosal release of histamine in patients with ulcerative colitis and in control subjects.

2. Rectal mucosal histamine release was significantly increased in ulcerative colitis, whether the patients were in remission or relapse. The highest values were found in active colitis, but in several such patients histamine release was within the control range. Measurement of rectal mucosal electrical potential difference suggested that increased mucosal histamine release in this group of patients was not due to enhanced epithelial permeability.

3. Rectal dialysis appears to be a useful method for assessing mucosal histamine production and the results obtained are consistent with the hypothesis that immediate hypersensitivity reactions could be of importance in some patients with ulcerative colitis.
Evidence in Vivo for a Circulating Natriuretic Substance in Rats after Expanding the Blood Volume
Authors: Knock Catherine A. , De Wardener H. E.
Published: August 2015

1. Five rats were volume expanded by infusing a volume of blood equivalent to one-third of the estimated blood volume. In six control experiments the same transfusion was given without expanding the blood volume, as an equal volume of blood was simultaneously removed. Sodium excretion increased significantly more after the blood volume was expanded than in the control experiments.

2. Pairs of rats placed on opposite scale pans of a trip balance were cross-circulated by means of arteriovenous bypasses. The blood volume of the rats could be kept constant by keeping the balance in equilibrium.

3. One of each pair of rats received a blood transfusion which either did or did not expand its blood volume. Sodium excretion was measured in the transfused rat and in the recipient rat, the blood volume of which was kept constant.

4. Sodium excretion in the six recipient rats cross-circulated with rats with an expanded blood volume was not significantly different from that in six recipient rats, cross-circulated with rats given a transfusion which did not expand the blood volume.

5. The cross-circulation experiments were repeated, with the difference that the urine of the transfused rat was reinfused. Under these conditions, sodium excretion in 11 recipient rats cross-circulated with blood volume expanded rats was significantly greater than in eight recipient rats cross-circulated with rats given a transfusion which did not expand the blood volume.

6. In cross-circulation experiments in which a blood transfusion was not given urine reinfusion of one rat did not affect sodium excretion of the other rat.

7. It is concluded that the rise in urinary sodium excretion which occurs in an isovolaemic recipient rat cross-circulated with a urine reinfused rat with an expanded blood volume is due to a change in the concentration of a circulating substance.
Further Evidence in Vivo for a Circulating Natriuretic Substance after Expanding the Blood Volume in Rats
Authors: Knock Catherine A.
Published: August 2015

1. The blood volume of 18 rats was expanded with blood with which they were equilibrated. In another 18 rats undergoing the same experimental protocol, the blood volume was not expanded.

2. In some rats the urine was reinfused.

3. A 1 ml portion of plasma obtained either 1 h after the blood volume was expanded, or at an equivalent time from the control rats, was injected intravenously into an assay rat.

4. The injection of plasma produced a gradual and significant rise in sodium excretion in the assay rat when it was obtained from an animal with an expanded blood volume, the urine of which was being reinfused.

5. When the increase in blood volume was sustained by a preceding bilateral nephrectomy, instead of urine reinfusion, the injection of 1 ml of plasma into an assay rat did not cause a rise in urinary sodium excretion.

6. It is concluded that the natriuresis involved in the assay rat was caused by a natriuretic substance in the 1 ml of plasma obtained from the blood-volume-expanded urine-reinfused rat.

7. The experiments suggest that the natriuretic substance is excreted in the urine and may be produced in the kidney.
Evidence That the Acute Hypotensive Effect of Captopril in Dogs is Not Wholly Explained by a Reduction of Plasma Angiotensin II and its Direct Vasoconstrictor Effect
Authors: Tree M. , Morton J. J.
Published: August 2015

1. Captopril infused into sodium-loaded dogs produced a fall in both blood pressure [117 ± 9.7 to 96.6 ± 11.4 (sd) mmHg] and plasma angiotensin II [11.0 ± 3.0 to 1.6 ± 1.3 (sd) pmol/l]. Plasma aldosterone fell while both blood angiotensin I and renin concentration rose.

2. Angiotensin II was infused at 2, 6, 18 and 54 ng min−1 kg−1 into sodium-depleted dogs. Plasma angiotensin II and arterial pressure both rose and were related in a dose-response curve.

3. On a separate occasion the same dogs were given an intravenous infusion of captopril (6 mg h−1 kg−1) and the angiotensin II infusion was repeated. Again plasma angiotensin II and arterial pressure rose but the dose-response curve was displaced downwards; a higher concentration of angiotensin II being required to produce the same blood pressure as in the dogs not given captopril.

4. These findings suggest that the acute hypotensive effect of captopril is not wholly explained by a decrease in plasma angiotensin II concentration and the consequent reduction of its acute vasoconstrictor effect.
Identification of Renin and Renin-like Enzymes in Rat Brain by a Renin-Specific Antibody
Authors: Dzau V. J. , Brenner Amy , Emmett Neremiah , Haber E.
Published: August 2015

1. The major angiotensin I-generating activity of rat brain extracts has a pH optimum different from that of renal renin and is not inhibited by renin specific antibody.

2. Affinity chromatography utilizing renin specific antibody, pepstatin and α-casein yielded fractions that resembled renal renin more closely with respect to antibody inhibition and pH optimum as well as an absence of the ability to hydrolyse haemoglobin.

3. We conclude that rat brain contains a host of enzymes with angiotensin I-generating activity including acid and neutral proteases and an enzyme with the immunochemical identity of renal renin. The biosynthetic origins of this renin-like protein remain uncertain.
Sternomastoid Muscle Function and Fatigue in Man
Authors: Moxham J. , Wiles C. M. , Newham D. , Edwards R. H. T.
Published: August 2015

1. A technique has been devised to measure the effect of stimulation frequency on the contraction force in an accessory muscle of respiration, the sternomastoid, in man. The frequency/force curve was found to be very similar to that of the quadriceps and adductor pollicis muscles.

2. Fatigue of the sternomastoid due to inspiratory loading or sustained maximum voluntary ventilation resulted in reduced force generation at low stimulation frequencies compared with maximum force. This type of fatigue frequently persisted for several hours.

3. If low frequency fatigue were to develop in patients with pulmonary disease it could have important consequences for the development of respiratory failure.
Converting Enzyme Inhibition during Chronic Angiotensin II Infusion in Rats: Evidence against a Non-Angiotensin Mechanism
Authors: Textor S. C. , Brunner H. R. , Gavras H.
Published: August 2015

1. To investigate the non-angiotensin effects of converting enzyme inhibition, angiotensin II was infused intravenously at 30 ng/min for 9 days in conscious rats to produce moderate blood pressure elevation. One group was given captopril (SQ 14 225) by gavage (100 mg/kg twice daily) and the other glucose.

2. After 7 days of captopril administration, enzyme blockade was confirmed by a tenfold greater depressor sensitivity to exogenous bradykinin and a markedly decreased plasma angiotensin converting enzyme activity.

3. Mean arterial pressure, heart rate and plasma renin activity were not different between captopril and glucose-treated groups in the presence of angiotensin II. Metabolic studies also revealed no long-term differences in water and food intake, weight change or sodium and potassium metabolism.

4. These findings suggest that, in the presence of angiotensin II, there is no detectable haemodynamic or metabolic effect of converting enzyme inhibition in rats and, therefore, that bradykinin plays little or no role in its long-term antihypertensive action.
Increase in Prostaglandins during Converting Enzyme Inhibition
Authors: Swartz S. L. , Williams G. H. , Hollenberg N. K. , Crantz F. R. , Levine L. , Moore T. J. , Dluhy R. G.
Published: August 2015

1. Because changes in the plasma concentration of angiotensin II and bradykinin appear inadequate to account completely for the hypotensive response to captopril, we measured changes in plasma prostaglandins in response to increasing doses of captopril in nine supine normal male subjects studied on both a high (200 mol/l) and low (10 mol/l) sodium intake.

2. On both the high and low sodium diets, captopril induced significant (P<0.01) increments in the 13,14-dihydro-15-keto metabolite of the vasodilatory prostaglandin E2, which correlated significantly with the fall in blood pressure (P<0.0001).

3. No significant changes were noted in the plasma levels of 6-keto-prostaglandins F1α or thromboxane B2, the stable products of prostacyclin and thromboxane A2 respectively.
Leucocyte Electrolytes and Sodium Efflux Rate Constants in the Hypertension of Pre-Eclampsia
Authors: Forrester T. E. , Alleyne G. A. O.
Published: August 2015

1. Leucocyte electrolytes were measured in pre-eclampsia and comparison was made with leucocytes from normal primigravidae and from the original pre-eclamptic subjects 6 months after delivery when blood pressure had returned to normal.

2. In pre-eclamptic subjects, leucocyte sodium was elevated and potassium depressed, and the rate constant for sodium efflux was depressed.

3. These changes returned to normal after delivery.

4. An increase in cellular sodium as a result of altered sodium pump activity may be the cause of hypertension in pre-eclampsia.
Characterization of the Sympatho-Facilitative Area Postrema Pathway
Authors: Barnes Karen L. , Ferrario C. M.
Published: August 2015

1. The mechanism by which the area postrema augments central sympathetic drive during electrical stimulation is presently unknown. This pathway may involve either direct facilitation of brain-stem vasomotor neurons or inhibition of the sympatho-inhibitory baroreceptor relay in the nucleus tractus solitarii.

2. The present study employed selective lesions within the solitary tract nucleus to assess the participation of the primary baroreceptor relay in the pressor response during electrical stimulation of the area postrema.

3. The magnitude of the pressor response was unchanged after destruction of the solitary tract and lateral solitary nucleus which centrally interrupted the baroreceptor reflex. However, microknife cuts through the medial solitary nucleus, which spared the carotid sinus reflex, significantly reduced the magnitude of the area postrema pressor response.

4. Previous anatomical studies support these results and confirm that, although the area postrema pressor pathway traverses the most medial portion of the solitary complex, it does not produce augmented sympathetic outflow by inhibition of the primary baroreflex relay.
Pseudohypertension in Sinoaortic-Denervated Rats
Authors: Norman R. A. , Coleman T. G. , Dent Ann C.
Published: August 2015

1. Mean arterial pressure was determined continuously over a 24-h period by computerized data collection in eight control and nine sinoaortic-denervated rats housed in standard-sized metabolic cages. In addition, direct and indirect pressure measurements were made while the rats were resting in a Lucite restrainer.

2. Pressure measurements made during restraint indicated that the baroreceptor-denervated rats were hypertensive: mean aortic pressure averaged 145 ± 3.4 mmHg (mean ± sem) in denervated rats vs 119 ± 2.8 mmHg in control rats (P<0.001), and tail-cuff pressure averaged 156 ± 5.4 mmHg compared with 121 ± 2.7 mmHg in the control group (P<0.001).

3. In contrast, continuous pressure monitoring showed the sinoaortic-denervated rats were normotensive (mean arterial pressure averaged 119 ± 4.7 mmHg vs 119 ± 3.1 mmHg in control rats).

4. Apparently arterial pressure is elevated during restraint in sinoaortic-denervated rats and pressure measurements made under these conditions give a false indication of hypertension.
Rapid Onset of Vascular Wall Protein Synthesis with Increase in Lability of Blood Pressure in Rabbits
Authors: MacLean A. G. , Bevan R. D. , Hume W. R. , Ransom R. W. , Bevan J. A.
Published: August 2015

1. Structural and functional changes resulting from baroreceptor denervation were studied in rabbits 4 days after surgery.

2. After section of the aortic and carotid sinus nerves, arterial pressure was characteristically labile although the mean pressures were not significantly different from those of control animals.

3. The responsiveness of isolated ear arteries and cephalic veins from deafferented animals to noradrenaline and electrical stimulation of their sympathetic innervation was similar in both groups.

4. Neuronal uptake of noradrenaline into arterial tissue was similar in both groups, although uptake into the cephalic veins of deafferented animals was less than in the control group.

5. [3H]Thymidine uptake, an index of DNA synthesis, was similar in both groups, radioautography revealing no difference in smooth muscle cell labelling.

6. Uptake of [3H]proline, an indicator of protein synthesis, by aorta, ear, brachial, basilar and renal arteries from deafferented animals was greater than in control animals.

7. Baroreceptor denervation altered protein metabolism in the arterial wall.
Haemodynamic Effects of Increasing Extracellular Potassium Concentration in ACTH-Induced Hypertension in Sheep
Authors: Scoggins B. A. , Coghlan J. P. , Denton D. A. , Fitzgerald Maureen , Graham W. F. , Mason R. T. , Schneider E. G.
Published: August 2015

1. ACTH administration (20 μg day−1 kg−1) to sheep produces hypertension associated with a raised cardiac output and hypokalaemia.

2. The aim of the present experiments was to detail the haemodynamic changes associated with restoration of the extracellular potassium concentration in sheep with ACTH-induced hypertension.

3. After 7 days of ACTH treatment potassium chloride (10 mmol/h) was infused for 3 days to restore plasma [K+] to the pre-ACTH value.

4. ACTH reduced plasma [K+] from 4.4 ± 0.1 to 3.2 ± 0.2 mmol/l but 3 days of potassium chloride infusion returned plasma [K+] to 4.3 ± 0.2 mmol/l.

5. ACTH increased mean arterial pressure from 67 ± 2 to 88 ± 1 mmHg in the first 7 days and it remained elevated during potassium chloride infusion (91 ± 5 mmHg on day 10).

6. Cardiac output rose with 7 days ACTH treatment from 4.9 ± 0.2 to 6.0 ± 0.6 l/min but fell progressively with potassium chloride infusion to 4.9 ± 0.3 l/min on day 10.

7. These studies suggest that potassium status or extracellular [K+] may play a role in determining the haemodynamic profile associated with steroid-induced hypertension.
Central Blood Volume in Spontaneously Hypertensive Rats and Wistar-Kyoto Normotensive Rats
Authors: Lundin S. , Folkow B. , Friberg P. , Rippe B.
Published: August 2015

1. Central blood volume and total blood volume were determined in spontaneously hypertensive rats and Wistar-Kyoto rats at two ages (6 and 12 weeks), representing ‘borderline’ hypertension and early ‘established’ hypertension.

2. A technique was used where plasma and erythrocyte indicators were injected into conscious rats. Blood volume in the cardiopulmonary compartment, present in the ‘resting’ awake steady state, could then be estimated by sudden freezing of the entire rat.

3. Twelve week-old spontaneously hypertensive rats showed a decreased total blood volume, and the fraction of blood contained in the cardiopulmonary area was significantly increased compared with that of normotensive Wistar-Kyoto rats.

4. In 6 week-old spontaneously hypertensive rats, total blood volume was only marginally decreased but here also a tendency towards centralization of the blood was seen.

5. Thus, along with the development of spontaneously hypertensive rat hypertension, a decreasing blood volume tends to become increasingly centralized to the cardiopulmonary area. Both neuro-hormonal influences and structural wall changes in the low-pressure capacitance side may contribute to this.
Blood Pressure Variability in Man: Its Relation to High Blood Pressure, Age and Baroreflex Sensitivity
Authors: Mancia G. , Ferrari A. , Gregorini L. , Parati G. , Pomidossi G. , Bertinieri G. , Grassi G. , Zanchetti A.
Published: August 2015

1. Intra-arterial blood pressure and heart rate were recorded for 24 h in ambulant hospitalized patients of variable age who had normal blood pressure or essential hypertension. Mean 24 h values, standard deviations and variation coefficient were obtained as the averages of values separately analysed for 48 consecutive half-hour periods.

2. In older subjects standard deviation and variation coefficient for mean arterial pressure were greater than in younger subjects with similar pressure values, whereas standard deviation and variation coefficient for heart rate were smaller.

3. In hypertensive subjects standard deviation for mean arterial pressure was greater than in normotensive subjects of similar ages, but this was not the case for variation coefficient, which was slightly smaller in the former than in the latter group. Normotensive and hypertensive subjects showed no difference in standard deviation and variation coefficient for heart rate.

4. In both normotensive and hypertensive subjects standard deviation and even more so variation coefficient were slightly or not related to arterial baroreflex sensitivity as measured by various methods (phenylephrine, neck suction etc.).

5. It is concluded that blood pressure variability increases and heart rate variability decreases with age, but that changes in variability are not so obvious in hypertension. Also, differences in variability among subjects are only marginally explained by differences in baroreflex function.
Asymptomatic Mild Hyperuricaemia: An Indicator of Nephrosclerosis in Essential Hypertension
Authors: Messerli F. H. , Frohlich E. D. , Dreslinski G. R. , Suarez D. H. , Aristimuno G. G.
Published: August 2015

1. Glomerular filtration rate, renal and systemic haemodynamics and intravascular volume were measured in 20 established essential hypertensive patients classified according to serum uric acid level into two groups (below 0.36 mmol/l, and above 0.54 mmol/l).

2. Although glomerular filtration rate was comparable between the two groups, renal blood flow was lower and renal vascular and total peripheral resistances were higher in the patients with the highest uric acid levels (P<0.02).

3. Cardiac output, heart rate and splanchnic blood flow were similar in both patient groups but arterial pressure tended to be higher in patients with high uric acid levels.

4. These data suggest that unexplained hyperuricaemia in patients with essential hypertension most likely reflects early renal vascular involvement, i.e. nephrosclerosis.
Value of Combined Intravenous Renal Arteriography and Pyelography in the Diagnosis of Renovascular Hypertension
Authors: Fournier A. , Cecile J. P. , Remond A. , De Fremont J. F. , Makdassi R. , Andrejak M. , Hardin J. M. , Grumbach Y.
Published: August 2015

1. The technique of combined intravenous renal arteriography and pyelography is described and results in 848 hypertensive patients are reported.

2. The procedure was tolerated better than Seldinger arteriography and the diagnostic accuracy for renal artery stenosis was 95%.

3. The prevalence of renovascular disease was 7%.

4. Cost-effectiveness calculations favour combined intravenous arteriography and pyelography rather than the usual approach based on assessment of the indications for Seldinger arteriography from clinical and urographic signs.
Human Leucocyte Antigens in Patients with Previous Essential Malignant Hypertension
Authors: Gudbrandsson T. , Herlitz H. , Hansson L. , Rydberg L.
Published: August 2015

1. Human leucocyte ABC antigens were determined by means of a lymphocytotoxicity test in 27 patients with previous essential malignant hypertension and in 500 blood donors.

2. In 18 patients with grade IV retinopathy human leucocyte antigen B15 (HLA B15) was found in 44%, as compared with 23% in the control subjects (P = 0.888).

3. All patients with HLA B15 had a positive family history for hypertension.

4. In 18 patients with grade IV retinopathy HLA B15 was found in eight whereas none of the nine patients with grade III retinopathy had this antigen (P = 0.039).

5. Of the 27 patients, 19 had a positive family history of hypertension and of these eight had HLA B15, whereas none of the eight patients with a negative family history had this antigen (P = 0.068).

6. The findings do not rule out that HLA B15 may be associated with the development of the malignant phase in patients with essential hypertension, but a statistically significant relationship could not be established.
Effect of Therapy on Left Ventricular Function in Hypertension
Authors: Khatri I. , Gottdiener J. , Notargiacomo A. , Freis E.
Published: August 2015

1. Twelve untreated hypertensive patients whose blood pressure was 171.8 ± 5.5 mmHg systolic and 119.7 ± 3.4 mmHg diastolic (mean ± sem) were treated aggressively with diuretics plus other antihypertensive agents. Echocardiograms were performed before, and 2 weeks, 3 months and 6 months after therapy. Blood pressures were lowered to an average of 142/98 mmHg over the 6 month period.

2. Mean velocity of circumferential fibre shortening rose from 1.1 ± 0.09 to 1.3 ± 0.06 diameters/s at 2 weeks and remained elevated at the end of 3 months (1.3 ± 0.03 diameters/s) (P<0.025), but returned to the control level in 6 months. Similarly, ejection fraction increased significantly during the same period from a control value of 65.1 ± 4.4 to 73.4 ± 1.8% (P<0.025) and persisted in this range at 3 months. At 6 months the ejection fraction had returned to pretreatment levels. There were significant reductions in left ventricular end-systolic and end-diastolic dimensions. Left ventricular mass index decreased from 182.3 ± 18.3 to 163.8 ± 12.4 g/m2 after 6 months of therapy.

3. These results indicate that in the early stages of blood pressure reduction there is a temporary increase in ejection phase indices, probably related to afterload reduction. The reduction in the left ventricular mass index suggests that increased cardiac muscle mass due to elevated blood pressure may be partially reversible after long-term reduction in blood pressure.
Disparate Effects of Methyldopa and Clonidine on Cardiac Mass and Haemodynamics in Rats
Authors: Ishise Shozo , Pegram Barbara L. , Frohlich E. D.
Published: August 2015

1. Wistar-Kyoto and spontaneously hypertensive rats were given either methyldopa (400 mg day−1 kg−1) or clonidine (0.1 or 0.3 mg day−1 kg−1) for 3 weeks commencing at 20 weeks of age.

2. Both drugs significantly decreased mean arterial pressure in spontaneously hypertensive but not Wistar-Kyoto rats. Heart rate was significantly increased in spontaneously hypertensive rats by methyldopa, whereas clonidine significantly decreased heart rate. The higher dose of clonidine also decreased heart rate in Wistar-Kyoto rats. Both cardiac output and total peripheral resistance decreased slightly, but not significantly, with both agents.

3. Methyldopa, but not the lower equipotent depressor dose of clonidine, reduced left ventricular hypertrophy in spontaneously hypertensive rats. However, the higher dose of clonidine also significantly decreased the heart to body weight ratio despite an increased total peripheral resistance presumably due to the α-adrenergic agonist effect.

4. Minimal changes in organ blood flows were noted with both drugs.

5. These results suggest that neither systemic haemodynamics nor central inhibition of adrenergic drive are primary factors responsible for the regression of hypertrophy.
Dose-Response Curve and Time Course of the Antihypertensive Effect of SKF 92 657, a β-Receptor-Blocking and Vasodilating Compound
Authors: Leonetti G. , Terzoli Laura , Sala Carla , Bianchini C. , Zanchetti A.
Published: August 2015

1. The antihypertensive effect of the new drug, SKF 92 657, a hydrazinopyridazine derivative, possessing both β-adrenoreceptor-blocking and vasodilating properties, was investigated in essential hypertension.

2. Single oral doses of 1.0 or 2.0 mg/kg did not produce any consistent decrease in blood pressure; 4.0 mg/kg was the threshold dose for a mild but not significant blood pressure reduction, whereas 8.0 mg/kg caused a significant and marked blood pressure decrease without clinically relevant changes in heart rate.

3. Continued administration of the drug for 7 days induced a significant and uniform reduction in blood pressure without tachycardia. The increase in systolic blood pressure and in heart rate caused by dynamic exercise was left unaffected by the drug.