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Biomedical subjects

P F Semple

Publications and source records attributed to P F Semple.

At least 37 records · Page 2Linked to original sources
PubMed1988

Calcium and magnesium in essential hypertension.

1. Because disturbances of calcium metabolism have been described in hypertension, measurements of plasma and serum concentrations of ionized calcium, total calcium, magnesium and renin were made in 38 patients with essential hypertension and age- and sex-matched control subjects. Urinary excretion of calcium, magnesium and sodium was also determined. 2. The mean serum concentration of ionized calcium was 1.23 +/- 0.04 (SD) mmol/l in the hypertensive group and 1.21 +/- 0.03 mmol/l in controls, and results were similar after correction for pH. There was a weak positive correlation between serum ionized calcium (pH 7.4) and systolic pressure (r = 0.26, P less than 0.02), but no correlation with plasma renin concentration. 3. Although the difference between serum total calcium concentration in the hypertensive (2.29 +/- 0.09 mmol/l) and control (2.26 +/- 0.07 mmol/l) subjects was not significant, there was a significant correlation between total calcium and systolic pressure (r = 0.23, P less than 0.05) which was maintained after correction for other variables. 4. There were no differences in plasma concentrations of parathyroid hormone or 1,25-dihydroxycholecalciferol between hypertensive and control subjects. 5. The hypertensive group showed higher urinary excretion of calcium (5.9 +/- 3.0 mmol/24 h) than controls (4.6 +/- 1.7 mmol/24 h), but the difference was not maintained after correction for sodium excretion. 6. Serum concentrations of magnesium were similar in the two groups, but urinary excretion of magnesium was significantly lower in hypertensive (3.7 +/- 1.3 mmol/24 h) than control (4.5 +/- 1.6 mmol/24 h) subjects and there was an inverse correlation between magnesium excretion and blood pressure (r = 0.3-0.35, P less than 0.01).

Adult↗
PubMed1987

Onset of action of captopril, enalapril, enalaprilic acid and lisinopril in normal man.

The effects of orally administered captopril, enalapril and lisinopril on plasma concentrations of angiotensin converting enzyme (ACE), angiotensin II (ANGII) and renin (PRC) were studied over a period of 6 hours in 6 normal subjects. A further 4 subjects received intravenous enalapril and enalaprilic acid (enalaprilat). Captopril (25 mg) by mouth caused a fall in pANGII that reached a nadir 30 to 40 minutes after administration but an effect was hardly apparent after 6 hours. Enalapril (10 mg) by mouth had less marked effects on pACE and pANGII with a decline in levels first apparent 1 hour after administration and the lowest levels reached between 3 and 6 hours. Lisinopril (10 mg) produced a progressive fall in pACE and pANGII from 1 hour to reach the lowest values 6 hours after treatment. Intravenous enalaprilat (5 mg) produced an immediate sustained fall in both pACE and pANGII but intravenous enalapril (7 mg) had a biphasic inhibitory effect.

Adult↗
PubMed1987

False localization of an aldosteronoma by dexamethasone-suppressed adrenal scintigraphy.

A patient with primary aldosteronism had bilateral adrenal tumours on computed tomography. Selenocholesterol scintigraphy showed uptake by the larger right adrenal gland and a tumour in the gland was also visualized by venography. In contrast, measurements of aldosterone concentrations in adrenal venous blood lateralized to the left side. At surgery the left adrenal gland contained an aldosteronoma and the right adrenal gland a large non-functioning adenoma. Thus, selenocholesterol scintigraphy incorrectly localized the functioning adrenal tumour.

Adenoma↗
PubMed1987

Neuropeptide Y in multiple endocrine neoplasia: release during surgery for phaeochromocytoma.

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.

Adrenal Gland Neoplasms↗
PubMed1987

Cation-dependent and cation-independent stages in regulation of the vascular angiotensin receptor after alteration of sodium balance in the rat.

The role of cations in vascular angiotensin receptor regulation has been investigated by radioligand receptor assay using a cell membrane fraction derived from mesenteric arterial muscle of the rat. In arterial membrane fractions from normal rats, the apparent receptor density varied with the ambient [Ca++] over the range, 0-10 mM. Receptor densities of 50 +/- 4, 102 +/- 4, and 156 +/- 5 fmol/mg membrane protein were obtained in low (0 mM), normal (4.8 mM), and high (25 mM) [Ca++], respectively. After 2 days of sodium loading, sodium depletion, and converting enzyme blockade altered receptor densities were detected in normal assay but not in high [Ca++] or low [Ca++], indicating changes in the relationship between [Ca++] and apparent receptor density. Similar results were obtained after 12 days of sodium loading or converting enzyme blockade. After 12 days of sodium depletion, there was no difference in receptor density between normal and high [Ca++] (44 +/- 5 fmol/mg protein) and the value obtained in low [Ca++] (27 +/- 2 fmol/mg protein) was significantly below that for all other groups. No change in receptor affinity was observed. These results suggest that there are two stages in vascular angiotensin receptor regulation; an initial masking-unmasking process which involves Ca++, and with prolonged agonist occupancy, an actual loss of receptors.

Angiotensin II↗
PubMed1986

Reduced number of angiotensin II receptors on platelets in insulin-dependent diabetes.

Angiotensin II receptors on platelets were studied in 13 patients with uncomplicated type I diabetes mellitus and in 15 age-matched normal subjects. Receptor density on cells from the diabetic patients was 15% lower than the normal subjects (5.2 +/- 0.8 SD sites/platelet in diabetic patients and 6.4 +/- 0.8 in normals, P less than 0.001), but there were no differences in receptor affinity as measured by Kd (4.9 +/- 1.5 X 10(-10) mol/l in diabetic patients and 5.4 +/- 1.4 X 10(-10) mol/l in normals). Plasma concentrations of renin and angiotensin II were similar in both groups. The reduced density of angiotensin II receptors on platelets from patients with insulin-dependent diabetes may reflect a generalized abnormality of angiotensin II receptor regulation.

Adult↗
PubMed1985

Potentiation of adrenaline-induced platelet aggregation by angiotensin II.

The effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10(-11) - 10(-7) M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (less than 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) M) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) M) had an inhibitory effect. Moreover, ANG II (10(-11) - 10(-7) M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2.

Angiotensin II↗
PubMed1985

Effects of potassium on sodium balance, renin, noradrenaline and arterial pressure.

To determine the effects of potassium on blood pressure and factors affecting blood pressure, we conducted a randomized, placebo controlled trial of a potassium chloride-based substitute for table salt in 23 patients with mild to moderate essential hypertension. In addition, the effects of potassium chloride on sodium balance were studied in 10 normal subjects. Potassium loading with 100 mmol/day over five days in these normal subjects caused a cumulative negative sodium balance of 138 +/- 35 mmol, similar in degree to that achieved by severe dietary sodium restriction. However, two weeks of potassium treatment (100 mmol/day) in patients with essential hypertension did not lower blood pressure (BP) either in the supine or upright positions (potassium treatment: mean BP 108 +/- 3 lying and 113 +/- 3 mmHg standing; placebo treatment: mean BP 109 +/- 3 lying and 115 +/- 3 mmHg standing). Patients found it difficult to tolerate the potassium-based salt substitute in the dose given. We conclude that it is premature to recommend an increase in potassium chloride intake as treatment for raised blood pressure.

Adult↗
PubMed1985

Regulation of platelet receptors for angiotensin II in man.

The effects of changes in dietary intake of sodium and potassium on 125I-angiotensin II binding to platelets were studied in normal subjects. We also defined binding to platelets from patients with essential hypertension and subjects with normal blood pressure. Restriction of sodium intake in normal subjects resulted in a decrease in the number of receptor sites from 6.2 +/- 0.3 sites/cell to 4.1 +/- 0.4 sites/cell (P less than 0.01) but there were no changes in affinity as measured by the Kd. Over a range of sodium intakes from 15 to 200 mmol/day there was a negative correlation between plasma concentration of angiotensin II and receptor site concentration (rs = 0.57, P less than 0.01). Changes in dietary potassium did not affect angiotensin II binding. Angiotensin II binding was also measured in 10 patients with essential hypertension (mean blood pressure [BP] 178/107 mmHg, plasma concentrations of renin [PRC] 12 +/- 2 microU/ml and angiotensin [pANG] II 14 +/- 2 pg/ml) and 10 subjects with normal blood pressure (mean BP 112/74 mmHg, PRC 13 +/- 2 microU/ml, pANG II 13 +/- 2 pg/ml). In the hypertensive patients, binding capacity and affinity (Kd = 5.0 +/- 0.6 X 10(-10) M, 5.7 +/- 0.8 sites/cell) were similar to those in the normotensive subjects (Kd = 4.9 +/- 0.8 X 10(-10) M, 5.4 +/- 0.5 sites/cell). Changes in sensitivity to angiotensin II in essential hypertension may not be determined at receptor level. Angiotensin II receptors in platelets respond to changes in sodium intake like receptors in arterial muscle.

Adult↗
PubMed1985

Angiotensin II effects on platelet function.

The effects of angiotensin II (ANG II) alone and in combination with other agonists on platelet aggregation, thromboxane B2 (TxB2) synthesis and cytosolic [Ca2+]i were investigated. Angiotensin II (10(-11)-10(-7) mol/l) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (< 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) mol/l) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) mol/l) had an inhibitory effect. Moreover, ANG II (10(-11)-10(-7) mol/l) augmented platelet responses to the TxA2 mimetic U44069. The facilitatory effect of ANG II on adrenaline-induced platelet aggregation was abolished by pretreatment of platelets with flurbiprofen. Thromboxane B2 synthesis by adrenaline-treated platelets was inhibited by ANG II. The results indicate that ANG II stimulation of agonist-induced platelet activation is due to potentiation of the effects rather than the synthesis of TxA2.

Angiotensin II↗
PubMed1984

Identification of the angiotensin II receptor in rat mesenteric artery.

Specific binding sites of high affinity and low capacity for 125I-angiotensin II have been identified in a membrane fraction derived from arterial arcades of the rat mesentery. Heterogeneity of binding sites and extensive tracer degradation necessitated the use of nonlinear regression methods for the analysis of radioligand binding data. Forward and reverse rate constants for the high affinity sites obtained by three experimental approaches were in good agreement and gave a dissociation equilibrium constant (Kd) of 19-74 pM (95% confidence interval). Affinities for a number of angiotensin-related peptides calculated from competitive binding curves were in the order 125I-angiotensin II = angiotensin II greater than angiotensin III greater than [Sar1,Ile8]angiotensin II greater than [Sar1,Gly8]angiotensin II. Angiotensin I and biochemically unrelated peptides had virtually no effect on binding of tracer angiotensin II. The divalent cations Mn2+, Mg2+ and Ca2+ stimulated 125I-angiotensin II binding at concentrations of 2-10 mM, as did Na+ at 50-100 mM. In the presence of Na+ or Li+, K+ had a biphasic effect. The chelating agents EDTA and EGTA were inhibitory, as were the thiol reagents dithiothreitol and cysteine. This study defined angiotensin II binding sites in a vascular target tissue of sufficiently high affinity to interact rapidly with plasma angiotensin II at physiological concentrations.

Angiotensin II↗
PubMed1984

Receptors for angiotensin II on platelets from man.

Platelets were prepared from peripheral venous blood on iso-osmotic density gradients of Percoll, resulting in a good recovery of cells (50-80%) which were relatively free of contaminating blood cells (erythrocyte less than 0.1%, leucocyte less than 1%). At 22 degrees C, specific binding of 125I-labelled angiotensin II (300 pmol/l) was time and temperature dependent, saturable, reversible and linear with cell concentration. Scatchard analysis of saturation curves revealed a single class of binding sites with Kd 1.5 +/- 0.4 X 10(-10) mol/l and total binding capacity 6.3 +/- 1.2 receptors/platelet. Similar values (Kd 2.4 +/- 0.7 X 10(-10) mol/l and binding capacity 6.5 +/- 1.0 receptors/cell) were obtained by displacement analysis. From kinetic studies the forward and reverse rate constants were 3.1 X 10(8) mol min-1 l-1 and 3.6 X 10(-2)/min giving a Kd of 1.2 X 10(-10) mol/l. The relative binding potencies for angiotensin II and analogues were: [Sar1, Thr8]ANG II greater than ANG II greater than ANG III greater than [Sar1, Ala8]ANG II greater than ANG I. Incubation with an extracellular marker (51Cr-labelled EDTA) demonstrated that binding of angiotensin II to platelets was not due to free fluid endocytosis.

Adult↗