bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of Peripheral Dopamine Receptors in Rats: A Mechanism for Novel Antihypertensive Agents
Authors: Lefegvre-Borg Francloise , Cavero Icilio 
Published: August 2015

1. The aim of this investigation was to provide support for the hypothesis that stimulation of peripheral dopamine receptors reduces sympathetic vasomotor tone and thus may be a mechanism for novel antihypertensive agents.
2. NN-Di-n-propyldopamine (DPDA: 0.03-0.1 mg min−1 kg−1 intra-arterially) produced sustained decreases in blood pressure measured from the cannulated tail artery in conscious spontaneously hypertensive rats.
3. This antihypertensive action of DPDA was antagonized by sulpiride but not by atropine, promethazine, propranolol or indomethacin.
4. DPDA failed to lower blood pressure in spontaneously hypertensive rats in which peripheral stores of catecholamines had been previously depleted with syrosingopine.
5. In the pithed atropine-pretreated spontaneously hypertensive rats in which the low blood pressure was elevated by electrical stimulation of the spinal cord, DPDA produced hypotensive effects which were antagonized by sulpiride. However, DPDA, in contrast to phentolamine, did not modify the blood pressure raised by an infusion of adrenaline.
6. In conclusion, the blood pressure-lowering action of DPDA is due to stimulation of dopamine receptors which decreases noradrenaline release and consequently sympathetic vasomotor tone. These receptors may be located on sympathetic ganglia or sympathetic endings innervating resistance vessels.
Plasma Catecholamine Levels and Vascular Response in Deoxycorticosterone Acetate Hypertension of Rats
Authors: Rascher W. , Dietz R. , Schomig A. , Weber J. , Gross F. 
Published: August 2015

1. In rats with deoxycorticosterone acetate (DOCA) hypertension basal plasma concentrations of noradrenaline and adrenaline correspond to those of sham-treated controls.
2. In DOCA-treated rats frusemide caused a more pronounced increase in plasma noradrenaline than in control rats. This difference was not observed for adrenaline.
3. In the isolated perfused hind-limb preparation the sensitivity to noradrenaline was already enhanced before blood pressure was elevated.
4. These results suggest that the adrenergic vascular tone is increased in DOCA hypertension in rats.
Hyperplasia of Rat Arteries Smooth Muscle Cells Associated with Development and Reversal of Renal Hypertension
Authors: Rorive G. L. , Carlier P. J. , Foidart J. M. 
Published: August 2015

1. Renal hypertension produces a marked and rapidly detectable hypertrophy of the rat aorta, due to smooth muscle cell hyperplasia and connective tissue deposition.
2. As we described previously for collagen synthesis, cell hyperplasia is a very early event which reaches a maximum at a time when the blood pressure is far from its highest level, and thereafter progressively decreases.
3. Reserpine prevents the vascular wall changes on the arterial as well as the venous side of the circulation. On the other hand, captopril although effective in preventing the blood pressure rise does not suppress the hyperplastic response.
4. The arterial hypertensive disease appears to be reversible, when renal ischaemia is corrected. The smooth muscle cell hyperplasia is, however, only partly and slowly reversible.
5. These data suggest that blood pressure is not the only determinant of the vascular wall response, and that the effect of a drug on the blood pressure does not necessarily predict the vascular wall response.
Effect of Morphine on Limb Capacitance and Resistance Vessels
Authors: Cohen R. A. , Coffman J. D. 
Published: August 2015

1. The actions of 15 mg of intravenous morphine on hand and forearm capacitance and resistance vessels were studied with venous occlusion plethysmography.
2. In contrast to a 5% increase in forearm venous volume, intravenous morphine caused a 26% decrease in hand venous volume. This hand venoconstriction was confirmed by finding an increase in hand venous tone. The effects of morphine on hand veins were attenuated by intra-arterial phentolamine and blocked by intravenous naloxone.
3. Whereas morphine had no significant effect on forearm resistance vessels, it caused a 70% reduction in hand vascular resistance.
4. Intra-arterial morphine had no local action on hand capacitance or resistance vessels.
5. Though the contrasting actions of morphine on hand and forearm capacitance vessels resulted in no important change in limb venous capacitance, the large reduction of cutaneous vascular resistance may contribute to haemodynamic benefit in patients with pulmonary oedema.
Direct Measurement of Hepatic Extraction of Bile Acids in Subjects with and without Liver Disease
Authors: Gilmore I. T. , Thompson R. P. H. 
Published: August 2015

1. The hepatic extraction ratio of 14C-labelled bile acids has been measured directly by hepatic vein catheterization in five patients without liver disease (glycocholic acid, three; cholic acid, two) and in 16 patients with histologically confirmed liver disease (glycocholic acid, seven; cholic acid, nine).
2. After intravenous administration of [14C]-glycocholic acid by bolus injection (two control subjects) or constant infusion (one control subject), directly measured hepatic extraction ratio was 0.91, 0.84 and 0.88, greater than that for indocyanine green. The extraction ratio of [14C]cholic acid in two subjects was 0.72 and 0.70, confirming a lower extraction of the unconjugated bile acid.
3. The hepatic extraction ratio of both bile acids was reduced in patients with chronic liver disease (range 0.07–0.69), although the extraction ratio of glycocholic acid remained normal in one patient with viral hepatitis.
4. Estimates of liver flow calculated from the extraction of [14C]glycocholic acid, but not cholic acid, correlated with those calculated from indocyanine green kinetics, although numbers were small.
5. Measurement of the hepatic extraction of individual bile acids, not previously reported in man, allows a more accurate description of the enterohepatic circulation.
The Turnover of Plasma Glucose and Free Fatty Acids in Vivo after Portacaval Anastomosis and Chronic Underfeeding in the Rat
Authors: Sarna G. S. , Cunningham V. J. , Tucker Sheron , Cremer Jill E. 
Published: August 2015

1. The metabolic status of rats after end-to-side portacaval anastomosis and the extent to which this differs from sham-operated animals, both fed and pair-fed, was investigated.
2. The body weights of sham-operated pair-fed rats consistently matched the weights of animals with a portacaval anastomosis at different times after the operation, whereas liver weights were significantly reduced in anastomosed animals as compared with the other groups.
3. Plasma glucose, insulin and the irreversible disposal rates for plasma glucose (determined by single intravenous injection of [6-3H]glucose) were similarly and significantly reduced for animals with a portacaval anastomosis and sham-operated pair-fed animals as compared with sham-operated fed control rats.
4. In contrast, plasma free fatty acid levels were significantly higher in animals with a portacaval anastomosis as compared with both sham-operated fed control and sham-operated pair-fed groups of animals. Turnover of plasma free fatty acids was measured in vivo by single intravenous injection of [1-14C]palmitic acid. The raised levels of plasma free fatty acids in animals with a portacaval anastomosis were principally due to reduced clearance and not to an increase in lipolysis.
5. Plasma β-hydroxybutyrate levels were similar in sham-operated fed control rats and animals with a portacaval anastomosis. Pair-fed values were three to four times greater than sham-operated fed control values and after portacaval anastomosis and increased further after a period of 24 h fasting. Values obtained for anastomosed animals increased only marginally after 24 h fasting and were significantly lower than pair-fed-animal values.
6. The rat with an end-to-side portacaval anastomosis may be characterized to be in a metabolic state equivalent to a chronically underfed animal in terms of reduced glucose turnover and plasma insulin concentrations but differs in respect to plasma free fatty acid turnover and plasma β-hydroxybutyrate concentrations.
A Comparison of the Effects of Intravenous Infusion of Individual Branched-Chain Amino Acids on Blood Amino Acid Levels in Man
Authors: Eriksson S. , Hagenfeldt L. , Wahren J. 
Published: August 2015

1., Intravenous infusions of l-valine (600 μmol/min), l-isoleucine (150 μmol/min), l-leucine (300 μmol/min) and a mixture of the three branched-chain amino acids (70% l-leucine, 20% l-valine, 10% l-isoleucine; 270 μmol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions.
2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P &lt; 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion.
3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion.
4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.
Passive Permeability in Experimental Intestinal Damage in Rats
Authors: Cobden I. , Rothwell Jill , Axon A. T. R. 
Published: August 2015

1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions.
2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose.
3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.
Age-Dependence of Noradrenaline Kinetics in Normal Subjects
Authors: Esler M. , Skews H. , Leonard P. , Jackman G. , Bobik A. , Korner P. 
Published: August 2015

1. The influence of age on the rate of spillover of noradrenaline into plasma, clearance of noradrenaline from plasma, and plasma noradrenaline concentration at rest was studied in 34 healthy subjects aged 20–69 years.
2. The plasma concentration of noradrenaline was dependent on age, values being higher in older subjects.
3. This age-dependence of plasma noradrenaline concentration was due principally to a reduced clearance of noradrenaline from the circulation in older subjects.
4. The rate of spillover of noradrenaline into plasma was little influenced by age. The higher plasma noradrenaline values found in older subjects do not seem to be due to an increase in sympathetic nervous system tone with aging.
Immunological Responses to Training in Conditioned Runners
Authors: Hanson P. G. , Flaherty D. K. 
Published: August 2015

1. We measured the concentrations of leucocyte subpopulations, immunoglobulins and complement in six well-conditioned runners before and after a typical 8-mile (12.8 km) training run at 70–75% of V̇o2 max.
2. Before running all components were within the normal range. Exercise failed to produce a significant rise in neutrophils. There was also no change in immunoglobulins or complement concentrations immediately or 24 h after exercise. Lymphocyte subpopulations were also unchanged except for a progressive rise in antibody-dependent cytotoxic effector cells (K-lymphocytes).
3. These results suggest chronic exercise training has no apparent adverse effect on circulating cellular or humoral immune components in healthy subjects. An increase in K-lymphocytes may provide added host defence capacity during periods of stress, although the mechanism of increase is unexplained.
Renal Phosphate Adaptation in Uraemic Dogs with a Remnant Kidney
Authors: Wen S.-F. , Stoll R. W. 
Published: August 2015

1. Clearance and micropuncture studies were performed in 27 dogs made uraemic by segmental infarction to examine the factors responsible for phosphate adaptation in chronic renal failure.
2. The animals were studied before and after extracellular volume expansion to 10% of body weight in the presence and absence of parathyroid glands. The results were compared with 19 normal dogs studied under similar experimental conditions.
3. In the dogs with a remnant kidney and intact parathyroids adaptation of phosphate transport was evident, with a high fractional excretion of phosphate. Thyroparathyroidectomy 3 days before study in the dogs with a remnant kidney and moderate renal failure reduced fractional excretion of phosphate to near normal values, indicating a major role of parathyroid hormone in phosphate adaptation. Extracellular volume expansion in these thyroparathyroidectomized uraemic dogs led to an exaggerated phosphaturic response with fractional excretion of phosphate returning towards the value in the uraemic dogs with intact parathyroid glands. Thus acute extracellular volume expansion could also contribute to the increase in fractional phosphate excretion, but extracellular volume probably plays a relatively minor role in the adaptation of phosphate excretion.
4. With more advanced renal failure fractional excretion of phosphate remained high, even after thyroparathyroidectomy, indicating that parathyroid hormone-independent factors become important for phosphate adaptation in the advanced stage of renal failure. The nature of parathyroid hormone-independent changes in fractional phosphate reabsorption in chronic renal failure remains unknown.
5. Proximal tubular fluid/plasma ultrafiltrate phosphate ratios were high in all groups of dogs with a remnant kidney regardless of thyroparathyroidectomy or the degree of renal failure. The non-specific nature of the proximal tubule pattern of phosphate transport indicates that phosphate adaptation is primarily determined by alterations in phosphate transport at a site distal to the proximal convoluted tubule. Alternatively, deep nephrons may play a greater role in determination of the overall phosphate adaptation in the chronically diseased kidney.
Lipid Peroxidation in Iron-Overloaded Spleens
Authors: Heys A. D. , Dormandy T. L. 
Published: August 2015

1. Iron-overloaded spleens from thalassaemic subjects showed a greatly increased susceptibility to free-radical oxidation (peroxidation) in vitro.
2. Iron content was the main but not the only variable governing susceptibility. Added ascorbate had a dose-dependent action either as an antioxidant or as a pro-oxidant, the direction of its effect depending mainly on the degree of iron overload. This has therapeutic implications.
Age-Related Decrease in Cardiac and Peripheral Vascular Responsiveness to Isoprenaline: Studies in Normal Subjects
Authors: Van Brummelen P. , Bühler F. R. , Kiowski W. , Amann F. W. 
Published: August 2015

1. Changes in forearm blood flow to intra-arterial infusion of isoprenaline and the chronotropic response to intravenous boluses of isoprenaline were measured in 15 healthy volunteer subjects, eight younger than 25 years and seven older than 50 years. Intra-arterial blood pressure and basal plasma renin activity, adrenaline and noradrenaline were also measured.
2. Young subjects exhibited a greater increase in forearm blood flow than old subjects, to all four doses of isoprenaline used, a greater cardiac isoprenaline responsiveness (measured by the increase in heart rate; P&lt;0.001) and a higher renin (P&lt;0.02).
3. Resting values of blood pressure, forearm blood flow, adrenaline and noradrenaline were not significantly different in young and old subjects. In the latter, noradrenaline correlated with forearm blood flow (r = −0.77, P&lt;0.05), forearm vascular resistance (r = 0.86, P&lt;0.02) and mean arterial pressure (r = 0.83, P&lt;0.02), whereas in the younger subjects forearm blood flow was related to adrenaline (r = 0.78, P&lt;0.05).
4. These data provide evidence for an age-related parallel reduction in cardiac, peripheral vascular and renal β-adrenoceptor-mediated responses.
The Relative Amounts of the Collagen Chains α1(I), α2 and α1(III) in the Skin of 31 Patients with Osteogenesis Imperfecta
Authors: Francis M. J. O. , Williams K. J. , Sykes B. C. , Smith R. 
Published: August 2015

1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent α1(III) and α1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the α1(I) to α2 chains of type I collagen has also been measured.
2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio α1 (III)/α1 (I) was significantly increased (P &lt; 0.001) and the ratio α1(I)/α2 significantly decreased (P &lt; 0.005) compared with age-matched control subjects.
3. In three infants with lethal (type II) osteogenesis imperfecta the ratio α1(III)/α1 (I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients.
4. The ratio of α1(I)/α2 and of α1(III)/α2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio α1(III)/α1 (I) was increased.
5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied.
6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the α1(I) chain rather than of the α2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.
Systemic and Forearm Haemodynamic and Metabolic Effects of Racemic Propranolol or d-Propranolol in Healthy Subjects
Authors: Hartling O. J. , Svendsen T. Lysbo , Trap-Jensen J. 
Published: August 2015

1. The immediate haemodynamic and metabolic effects of intravenous administration of dl-propranolol and d-propranolol were studied in healthy male subjects at rest and during dynamic forearm exercise. The dose of dl-propranolol and of d-propranolol was 0.1 and 1.0 mg/kg body weight respectively.
2. dl-Propranolol reduced heart rate significantly at rest, during forearm exercise and post-exercise, whereas d-propranolol had a lesser effect on heart rate which was significant only at the end of the exercise period. Arterial blood pressure and forearm blood flow were unchanged after either drug.
3. Both drugs reduced the release of lactate from the exercising forearm. Forearm exchange of oxygen, glucose, free fatty acids and triglycerides remained unchanged.
4. The arterial blood glucose concentration increased after d-propranolol, but was unchanged after dl-propranolol. The arterial serum free fatty acid concentration decreased after dl-propranolol, but was not changed after d-propranolol. Arterial concentrations of lactate and triglycerides were not influenced by the drugs.
5. The chronotropic response to β-adrenoceptor blockade appears to be stereoselective, suggesting specific blockade of β-adrenoceptors. Metabolic responses to β-adrenoceptor blockade are difficult to explain in terms of the known adrenoceptor system and may be due to nonspecific actions of β-adrenoceptor antagonists. An exception is inhibition of lipolysis, which is probably mediated via β-adrenoceptors.
An Increase in a Circulating Inhibitor of Na+,K+-Dependent ATPase: A Possible Link between Salt Intake and the Development of Essential Hypertension
Authors: MacGregor G. A. , Fenton S. , Alaghband-Zadeh J. , Markandu N. D. , Roulston J. E. , De Wardener H. E. 
Published: August 2015

1. The plasma's ability to stimulate guinea-pig renal glucose 6-phosphate dehydrogenase (G6PD) in vitro was measured by a cytochemical technique in 23 normotensive subjects and 19 patients with hypertension, all of whom were studied on their normal sodium intake. The ability of plasma to stimulate renal G6PD was significantly (P &lt; 0.001) increased in the hypertensive patients (mean 195 ± 52 units/ml) compared with the normotensive subjects (mean 22.2 ± 5.8 units/ml). In all 42 individuals, there was a significant correlation between diastolic pressure and the ability of plasma to stimulate G6PD (r = 0.69 P &lt; 0.001).
2. The ability of plasma to stimulate G6PD was greatest in the hypertensive patients with values of plasma renin activity below the normal range. In the normotensive subjects the ability of plasma to stimulate G6PD was significantly greater in the older subjects.
3. As the ability of plasma to stimulate G6PD reflects its ability to inhibit Na+,K+-dependent ATPase, these results suggest that patients with essential hypertension have an increase in a circulating inhibitor of Na+,K+-ATPase. The results support the hypothesis that a rise in a circulating sodium transport inhibitor may, in part, be responsible for the rise in blood pressure in essential hypertension, and may form the link between salt intake, abnormalities of sodium transport and a rise in blood pressure.