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Biomedical subjects

A C Shore

Publications and source records attributed to A C Shore.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effect of potassium depletion on renal tubular function in the rat.

1. In order to investigate the effects of K+ depletion on renal function, micropuncture studies were performed on anaesthetized rats which had been kept on a K+-deficient diet for 2 weeks; results were compared with those from control animals. 2. In the K+-depleted animals, values for total glomerular filtration rate and single-nephron filtration rate were significantly lower than in controls. Urine osmolality was also reduced; this was associated with reductions in the osmolality, Na+ concentration and K+ concentration of papillary interstitial fluid. No significant difference between urine and papillary osmolality was observed. 3. Fractional reabsorption by the proximal convoluted tubule was enhanced in the K+-depleted animals; end-proximal fluid delivery was markedly reduced. 4. Absolute, but not fractional, delivery of K+ to the beginning of the distal tubule was reduced in the K+-depleted animals. In contrast to observations in control rats, no net secretion of K+ into the distal tubule occurred and there was indirect evidence of K+ reabsorption in the collecting duct. 5. K+ depletion was associated with reductions in the delivery of Na+ and water to early and late regions of the distal tubule, whereas excretion rates of Na+ and water were unaffected. 6. It is suggested that the reduction in Na+ delivery to the loop of Henle (arising from the changes in filtration rate and proximal tubular reabsorption) might contribute to the reduced medullary osmotic concentration observed during K+ depletion. Reductions in fractional reabsorption of Na+ and water in the collecting duct might result from lowered plasma aldosterone levels and the reduced medullary osmolality.

Animals↗
PubMed1988

Plasma atrial natriuretic peptide in essential hypertension. Comparison with normotensive subjects and effects of changes in dietary sodium intake.

Plasma levels of atrial natriuretic peptide (ANP) in 106 patients with essential hypertension with a supine mean blood pressure (mean +/- SEM) of 128.9 +/- 1.6 mmHg and not on treatment were significantly higher than those in 47 normotensive subjects (supine mean blood pressure 93.9 +/- 1.2 mmHg) with mean values of 17.2 +/- 1.1 and 8.6 +/- 0.6 pg/ml, respectively (P less than 0.001). Similar results were found in a subgroup of 35 hypertensive patients identically matched in terms of age, sex, and race with 35 normotensive subjects. Plasma levels of ANP were correlated significantly with age in normotensive subjects and with age and blood pressure in the hypertensive patients. In 12 hypertensive patients studied on a low (10 mmol sodium/day), on their usual sodium intake (around 120 mmol sodium/24 hr) and on a high (350 mmol sodium/day) intake, plasma ANP increased approximately twofold by the fifth day of the high sodium intake, but there was no significant difference between the plasma levels on their usual sodium intake and those on the fifth day of the low sodium intake. Supine mean blood pressure on the patients' usual sodium intake was 119.3 +/- 2.7 mmHg and was reduced to 110.0 +/- 3 mmHg by the fifth day of the low sodium intake (P less than 0.005). However, there was no significant difference between the blood pressure levels on their usual and high sodium intake (118.3 +/- 3.0 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

A randomized crossover study to compare the blood pressure response to sodium loading with and without chloride in patients with essential hypertension.

Six patients with essential hypertension underwent a randomized cross over design study to investigate the effect of supplementing a 10 mmol/day sodium diet for a period of 5 days with either 120 mmol sodium chloride (Slow Sodium, Ciba, Horsham, UK) or 122 mmol sodium in the presence of other anions, mainly phosphate (Phosphate, Sandoz, Feltham, UK). With both sodium salts, urinary sodium excretion was increased. The calculated amount of sodium retained was similar for both the sodium chloride and sodium phosphate periods. However, with the addition of sodium chloride to the low-salt diet, there were increases in supine mean blood pressure whereas with the addition of sodium phosphate no change in mean blood pressure occurred. The supine mean blood pressure after supplementation with sodium chloride (119.8 +/- 4.3 mmHg) was significantly greater than that after sodium phosphate (113.3 +/- 4.5 mmHg), similarly, the standing mean blood pressure was greater after addition of sodium chloride than of sodium phosphate (122.3 +/- 4.20 versus 115.4 +/- 3.0 mmHg). With both salts there were similar but non-significant increases in weight and reductions in plasma renin activity (PRA) and plasma aldosterone (PA).

Blood Pressure↗
PubMed1987

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month's treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.

Captopril↗
PubMed1987

Plasma immunoreactive atrial natriuretic peptide and changes in dietary sodium intake in man.

Plasma levels of immunoreactive atrial natriuretic peptides (IrANP) have been measured in 8 normotensive subjects during alterations in dietary sodium intake. Subjects were studied on their normal sodium intake (2 days) then on a low sodium intake (7 days, 10 mmols Na+/day) and subsequently on a high sodium intake (14 days, 350 mmols Na+/day with the diets being given in a fixed order. Plasma levels (mean +/- S.E.M.) of IrANP on a normal sodium diet were 7.3 +/- 0.9 pg/ml; 4.5 +/- 0.8 on the 7th day of a low sodium intake and 10.8 +/- 1.3; 16.6 +/- 3.3; 15.5 +/- 4.2; 15.6 +/- 2.3 pg/ml respectively or the 1st, 3rd, 10th and 14th day on the high sodium intake. Changes in plasma IrANP were closely associated with changes in urinary sodium excretion. These results suggest that in normal subjects the atrial natriuretic peptides may play an important role in the adaptation to increases in dietary sodium intake both on a short and on a longer term basis.

Adolescent↗
PubMed1987

Plasma atrial natriuretic peptide: its relationship to changes in sodium intake, plasma renin activity and aldosterone in man.

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP), plasma renin activity, aldosterone and vasopressin were measured in 11 normotensive subjects on a low (10 mmol/day), a normal (150 mmol/day) and a high (350 mmol/day) sodium intake. Plasma levels of IrANP increased significantly with increasing dietary sodium intake with levels (means +/- SD) of 3.9 +/- 2.1 pg/ml on the fifth day of the low sodium diet, 6.1 +/- 3.4 pg/ml on the fifth day of the normal sodium diet and 11.4 +/- 4.6 pg/ml on the fifth day of the high sodium diet. Plasma renin activity and aldosterone decreased significantly with increasing sodium intake whereas plasma vasopressin was highest on the high sodium intake. These results suggest that the atrial peptides may be a new and important component in the overall control of sodium and water balance during increased sodium intake.

Adult↗
PubMed1987

Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man.

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5 +/- SEM 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 +/- 2.4 pg/ml) to day 7 (15.1 +/- 2.6 pg/ml). The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium 'escape' occurred by days 4 to 7. These results support the concept that ANP could play an important hormonal role in over-coming the sodium-retaining effects of mineralocorticoids in man.

Adult↗
PubMed1987

Dissociation between plasma atrial natriuretic peptide levels and urinary sodium excretion after intravenous saline infusion in normal man.

1. Plasma immunoreactive atrial natriuretic peptide (ANP) and urinary sodium excretion were measured in six normal male subjects before, during and for 195 min after a 60 min infusion of 2 litres of saline (0.9% NaCl, 308 mmol of Na+). 2. During the saline infusion, there was a significant increase in plasma ANP and urinary sodium excretion and a significant decrease in plasma renin activity, aldosterone, albumin, creatinine and packed cell volume. 3. The maximal rise in mean plasma ANP occurred 15 min after stopping the infusion and the maximal rise in mean urinary sodium excretion in the collection period 30 min later. 4. Plasma ANP then decreased so that by the end of the study the level was the same as before the saline infusion. However, at this time, 195 min after the saline infusion was stopped, there was still a net positive sodium balance of 220 mmol and urinary sodium excretion remained significantly elevated. 5. Our results are compatible with the concept that increased ANP secretion may play a role in the immediate increase in sodium excretion after a saline load. However, they also suggest that other mechanisms may be more important for the longer term increase in sodium excretion.

Adult↗
PubMed1987

Validation of beat by beat pulsed Doppler measurements of ascending aortic blood velocity in man.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.

Aorta↗
PubMed1987

Does oral calcium supplementation lower high blood pressure? A double blind study.

Eighteen unselected patients with untreated mild to moderate essential hypertension, whose average supine blood pressure after 2 months' observation on no treatment was 154/103 mmHg, were entered into a double-blind randomized crossover study of 1 month's treatment with calcium lactate gluconate (40 mmol of elemental calcium/day) and treatment with placebo for a further month. Despite a significant increase in total plasma calcium (P less than 0.01) and in 24-h urinary excretion of calcium (P less than 0.025) while taking calcium lactate gluconate, there was no fall in blood pressure with calcium supplementation compared to treatment with placebo.

Adult↗
PubMed1987

A double-blind study of the blood pressure lowering effect of a thiazide diuretic in hypertensive patients already on nifedipine and a beta-blocker.

Twelve hypertensive patients who were already on treatment with atenolol (100 mg once daily) and nifedipine as tablets (20 mg twice daily) were entered into a double-blind, randomized crossover study of the addition of 1 month's treatment with either bendrofluazide (5 mg once daily) or a matching placebo. The addition of bendrofluazide to the combination of atenolol and nifedipine did not cause any statistically significant fall in the blood pressure 2 h after the last dose of nifedipine compared to treatment with placebo [bendrofluazide: 135.2 +/- 5.1/89.8 +/- 2.5 (mean +/- s.e.), versus placebo: 132.1 +/- 4.6/89.9 +/- 3.1 mmHg; P = NS]. However, 12 hours after the last dose of nifedipine blood pressure tended to be lower whilst on bendrofluazide compared with placebo. Plasma urate levels were significantly higher on the diuretic compared to placebo (461 +/- 27 versus 396 +/- 21 mumol P less than 0.001). Plasma potassium was lower on the diuretic compared to placebo (3.59 +/- 0.12 vs 3.76 +/- 0.10) but this difference just failed to reach statistical significance. The results of this study suggest that a thiazide diuretic has little additive effect on blood pressure in patients already on treatment with atenolol and nifedipine, particularly when nifedipine is maximally effective. However, the addition of a diuretic does have potentially deleterious metabolic effects.

Adult↗
PubMed1987

Captopril and nifedipine in combination for moderate to severe essential hypertension.

The effects of the addition of a calcium entry antagonist, nifedipine (20-mg tablet twice a day), to an angiotensin converting enzyme inhibitor, captopril (25 mg three times a day), and the addition of captopril to nifedipine were observed in two separate studies in patients with essential hypertension. After 4 weeks of captopril therapy alone, mean arterial pressure fell by 12 mm Hg, and with the addition of nifedipine to captopril for a further month, blood pressure fell by an additional 10 mm Hg. In a separate group of patients treated with the same doses, mean arterial pressure fell by 17 mm Hg with nifedipine treatment alone; when captopril was added to the nifedipine therapy for an additional month, mean arterial pressure fell by a further 11 mm Hg. These blood pressures were measured 2 hours after the last dose; however, there was less of a fall in blood pressure when it was measured 12 hours after the last dose. This study confirms that captopril and nifedipine have a marked additive effect on blood pressure in whichever order they are given, but it shows that the combination is relatively short-acting.

Adult↗
PubMed1987

Nifedipine and acebutolol in combination for the treatment of moderate to severe essential hypertension.

In a randomised, crossover study of patients with moderate to severe essential hypertension, the effects of the calcium entry antagonist nifedipine and the beta-receptor blocking drug acebutolol were studied on their own, and in combination. After 4 weeks of nifedipine tablets 20 mg twice daily (Adalat, Bayer), mean supine blood pressure (BP) fell by 20 mmHg and after 4 weeks of acebutolol 200 mg twice a day (Sectral, May & Baker) by 11 mmHg. When nifedipine and acebutolol were given in combination in the above doses for 4 weeks, there was a significantly greater fall in BP than with either agent alone, supine mean arterial pressure falling by 27 mmHg. The above BPs were measured 2 h after the last dose of tablets. Measurements 12 h after the last dose showed smaller falls in BP, with a significantly greater fall with combination treatment than with acebutolol alone. The fall in BP 12 h after the last dose of the combination was greater than with nifedipine alone but this difference was not statistically significant. This randomised, controlled study showed that nifedipine and acebutolol have a marked additive effect on BP which is sustained for at least 12 h after treatment.

Acebutolol↗
PubMed1987

Serum ionized calcium and pH: effects of blood storage, some physiological influences and a comparison between normotensive and hypertensive subjects.

The effects on serum ionized calcium (ICa) and pH of different storage conditions of blood or serum, and of physiological influences such as over-ventilation, food intake and dietary sodium intake have been investigated. Temperature and time-related changes in ICa occurred with storage and were minimized by immediate separation of serum and storage at 4 degrees C, (6 h or less). Elevation of serum ICa and a fall in pH accompanied increased salt intake; over-ventilation induced an elevation of serum pH and a reduction in ICa. Day-to-day intra-individual variation of ICa was 0.93%. We proceeded to examine a group of age-, sex- and race-matched hypertensive and normotensive subjects under standardized conditions designed to minimize such technical and physiological artefacts. ICa was not significantly different in the two groups; however, serum pH was significantly elevated in the hypertensive group. In the combined group of normotensive and hypertensive subjects, serum pH was significantly correlated with blood pressure. Exclusion of the black subjects from the analysis did not alter the findings.

Adult↗
PubMed1986

Raised circulating levels of atrial natriuretic peptides in essential hypertension.

Plasma levels (mean +/- SD) of immunoreactive atrial natriuretic peptides (ANP) were significantly higher in 28 hypertensive subjects (17.1 +/- 13.8 pg/ml) than in 24 normotensive subjects (8.4 +/- 3.7 pg/ml) matched as far as possible for age, sex, and race. All subjects were studied on their normal dietary sodium intake. In the normotensive subjects ANP levels were significantly correlated with age but not with blood pressure, whereas in the hypertensive subjects ANP levels were significantly correlated with systolic blood pressure but not with age. These findings may indicate a compensatory reaction to a diminished renal capacity for sodium excretion, in response to increasing age in normotensive subjects and to higher blood pressure in hypertensive subjects.

Adult↗
PubMed1986

Effect of increasing calcium intake on urinary sodium excretion in normotensive subjects.

Eight normotensive subjects were studied in a randomized crossover trial of a high calcium diet (1800 mg of calcium/day) for a week against a low calcium diet (200 mg of calcium/day) for a further week. The subjects were placed on a diet containing 200 mg of calcium/day throughout the study and the high calcium diet was achieved by supplementing the low calcium diet with calcium glubionate and galactogluconate. Sodium and potassium intake were kept constant throughout the study. Twenty-four hour urinary sodium, potassium, calcium and phosphate were measured daily. In spite of a highly significant increase in calcium excretion from the low to the high calcium diet (P less than 0.0001), there was no increase in sodium or change in potassium excretion with the increased calcium intake. A transient but significant fall in urinary sodium excretion was observed up to the fourth day of the high calcium diet (P = 0.021). Twenty-four hour urinary phosphate excretion fell significantly on the high calcium diet (P less than 0.0001). Body weight, blood pressure, plasma renin activity, aldosterone, plasma creatinine and serum ionized calcium did not change. These results suggest that a short-term increase in calcium intake in normotensive subjects does not increase urinary sodium and potassium excretion.

Adult↗
PubMed1986

Evidence for increased levels of a circulating ouabainlike factor in essential hypertension.

The effect of plasma from normotensive and hypertensive subjects on the binding of [3H]ouabain on human erythrocytes was investigated. The binding of [3H]ouabain on human erythrocytes was saturable and highly specific; linear Scatchard plots indicated the presence of a single type of binding site. Human plasma decreased the binding of [3H]ouabain on its receptor to a greater extent than could be accounted for by the plasma potassium concentration. The level of this circulating ouabainlike factor (or factors) was quantitated using a radioreceptor assay. Plasma from 22 hypertensive subjects (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg) displayed higher levels than that from 24 normotensive subjects; furthermore there was a positive and significant correlation (r = 0.42, n = 46, p less than 0.004) between the ouabainlike content and the individual subject's systolic blood pressure. The receptor assay described is relatively simple and should be useful for further work on the nature and clinical importance of the endogenous ouabainlike factor.

Adult↗