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Biomedical subjects

P F Semple

Publications and source records attributed to P F Semple.

At least 55 records · Page 3Linked to original sources

Potassium influx into erythrocytes in essential hypertension.

Sodium plus potassium (Na+K) cotransport in erythrocytes of patients with essential hypertension has mainly been studied elsewhere by measuring net outward frusemide-sensitive Na and K movements. We compared K influx (tracer 86 Rubidium) in control subjects and hypertensives who had never previously been treated for hypertension. The cotransport K influx rates in controls and hypertensives were 0.44 +/- 0.02 (mumol/ml cells/h; mean +/- s.e.; n = 20) and 0.67 +/- 0.06 (mumol/ml cells/h; mean +/- s.e.; n = 23) respectively. The active influxes were 1.03 +/- 0.03 and 2.06 +/- 0.13 (mumol/ml cells/h; mean +/- s.e.) respectively. The variance of both parameters was significantly greater in the hypertensive group but, taking this into account, the differences were significant (P less than 0.01).

Adult↗

Relation of blood pressure with body and plasma electrolytes in Conn's syndrome.

Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.

Adult↗

Angiotensin II receptors in resistance vessels.

We have studied binding of 125I-angiotensin II (AII) to a membrane fraction prepared from mesenteric arterial arcades of the rat. Two problems were encountered: heterogeneity of binding sites and appreciable degradation of tracer that could not be inhibited without adversely affecting binding capacity. Analysis of binding results was carried out using a non-linear regression method allowing correction for tracer and receptor degradation and direct estimation of binding constants. From saturation and dissociation curves it was apparent that there were two classes of binding sites. KD of the high affinity site was within the physiological range of plasma AII concentration at between 0.05 and 0.5 nM. Calcium, magnesium and manganese increased binding capacity, whereas EDTA and EGTA had the opposite effect. Potassium increased binding capacity but had a biphasic effect in the presence of sodium.

Angiotensin II↗

The decision on surgery in renal artery stenosis.

Eighty-six hypertensive patients with arteriographic evidence of renal artery stenosis presented between 1968 and 1979. Thirty-nine subsequently underwent surgery and were followed thereafter for at least one year. In 54 per cent blood pressure was reduced to within one standard deviation of the mean for a normal individual of the same sex and age. A further thirty-one per cent of patients were 'improved', but needed hypotensive drugs to maintain blood pressure within this range. In the remaining 15 per cent of patients the operation did not reduce blood pressure. The purpose of the study was to assess our ability to predict this varies surgical outcome using clinical observations and special tests. The latter included measurement of plasma renin concentration in both peripheral vein and renal vein plasma, catheterization of both ureters and studies of the response of blood pressure to brief infusion of saralasin. No single observation or test, no combination of observations or tests and no discriminant function clearly separated patients in whom surgery would succeed from those in whom it would fail. Renal vein renin ratio was the best test; all patients with a ratio greater than 2.0 underwent successful surgery, but so too did some patients with a lower ratio. We also analysed the factors which had influenced our decision to undertake special investigations in 65 of the 86 patients and, having done these investigations, to recommend surgery in 39. No single factor seemed to have had overriding importance in making these decisions.

Adolescent↗

Relation of arterial pressure with body sodium, body potassium and plasma potassium in essential hypertension.

1. Exchangeable sodium (NaE), plasma electrolytes and arterial pressure were measured in 121 normal subjects and 91 patients with untreated essential hypertension (diastolic greater than 100 mmHg), 21 of whom had low-renin hypertension. Plasma concentrations of renin, angiotensin II and aldosterone were measured in all hypertensive patients, total body sodium, total body potassium and exchangeable potassium (KE) in some patients. 2. Mean NaE was not different in normal and hypertensive subjects provided the two groups were matched for leanness index. In the subgroup of young hypertensive patients aged 35 years or less mean NaE was below normal. NaE was not related to arterial pressure in normal subjects but in hypertensive patients there were positive and significant correlations of arterial pressure with NaE and with total body sodium. 3. NaE and total body sodium increased with age in hypertensive but not in normal subjects. Partial regression analysis suggested that the correlation of NaE with arterial pressure was not explained by an influence of age. 4. Mean NaE was not increased and mean KE was not decreased in patients with low-renin hypertension. 5. Plasma potassium concentration, KE and total body potassium correlated inversely and significantly with blood pressure in hypertensive patients. These correlations were more marked in young than in old patients. 6. Multiple regression analysis showed that the combination of NaE and plasma potassium concentration 'explained' more of the variation of systolic blood pressure in hypertensive patients than it did in normal subjects. Plasma potassium concentration 'explained' more of the variation in young hypertensives and NaE 'explained' more in older patients. 7. Our findings suggest than changes of plasma and body potassium are important in the earlier stages of essential hypertension and that changes of body sodium become important later.

Adult↗

Angiotensin II in human cerebrospinal fluid may be an immunoassay artifact.

1. Concentrations of angiotensin II (ANG II) were measured by radioimmunoassay in cerebrospinal fluid and plasma from neurosurgical patients and patients having spinal anaesthesia. Cerebrospinal fluid concentrations of renin, renin substrate and ANG I were also measured. 2. Cerebrospinal fluid concentrations of ANG II measured with antiserum 30/VI were low in neurosurgical patients (mean 6 pmol/l, range < 2 - 12 pmol/l, n = 7) and lower in spinal anaesthesia patients (mean 1 pmol/l, range < 2 - 4 pmol/l, n = 14) and unrelated to concurrent plasma concentrations of ANG II. 3. A second more sensitive immunoassay with ANG II antiserum 9/P gave higher cerebrospinal fluid concentrations of ANG II in spinal anaesthesia patients (mean 15 +/- 1 pmol/l, n = 7, P < 0.01). 4. Paper chromatography showed that the ANG II immunoreactive material measured with antiserum 9/P was not ANG I, ANG II, ANG II-(2-8), ANG II-(3-8) or ANG II-(4-8). 5. The concentration of ANG I in cerebrospinal fluid was low (4 +/- 0.04 pmol/l, n = 7). No renin was detected (n = 32) and the concentration of renin substrate was 45 +/- 2.6 nmol/l (n = 24). 6. Much of the immunoreactive ANG II in human cerebrospinal fluid is an immunoassay artifact.

Aged↗

Increased 18-hydroxycorticosterone responses to frusemide in essential hypertension.

Plasma concentrations of angiotensin II (AII), aldosterone, 18-hydroxycorticosterone and cortisol were measured in seven patients with benign essential hypertension and in seven age-matched control subjects before, and at frequent intervals for 2 h after the intravenous injection of frusemide (40 mg). In the normal subjects, significant increases in the plasma levels of AII, aldosterone and 18-hydroxycorticosterone were apparent from 15 min after diuretic administration. The integrated responses of each hormone to frusemide administration were calculated. Aldosterone and AII responses to the diuretic were closely related, although three hypertensive patients had normal integrated aldosterone responses despite subnormal increases in the plasma concentrations of AII. The integrated 18-hydroxycorticosterone responses were greater in the hypertensive (median 970 nmol.h h-(1).1-(1)) than in the normal subjects (median 180 nmol.h-(1).1-(1)), P<0.05. Some patients with a raised blood pressure appear to have an enhanced adrenal corticosteroid response to frusemide; this probably reflects an increased sensitivity to angiotensin II.

18-Hydroxycorticosterone↗

The effects of hemorrhage and sodium depletion on plasma concentrations of angiotensin II and [des-Asp1]angiotensin II in the rat.

Plasma concentrations of angiotensin II (PAII) and [des-Asp1]angiotensin II (Pdes-Asp1-AII) were measured before and after hemorrhage and acute and chronic depletion of sodium. Graded hemorrhage increased PAII from 30 +/- 5 to 220 +/- 41 and 989 (526-1290) pmol/liter and Pdes-Asp1-AII from 47 +/- 11 to 216 +/- 72 and 532 +/- 178 pmol/liter. Furosemide increased PAII from 26 +/- 4 to 178 +/- 37 but did not change Pdes-Asp1-AII (31 +/- 3 to 31 +/- 4 pmol/liter). Deprivatin of dietary sodium increased PAII from 25+/- 6 to 136+/- 22 pmol/liter and Pdes-Asp1-AII from 41 +/- 4 to 71 +/- 15 pmol/liter. The ratio of PAII to Pdes-Asp1-AII was increased by all three stimuli (P < 0.05 to P < 0.001). Pdes-Asp1-AII II is unlikely to mediate the effects of hemorrhage and changes in sodium balance on aldosterone secretion in the rat.

Angiotensin II↗

Suppression of plasma ACTH concentration by angiotensin II infusion in normal humans and in a subject with a steroid 17 alpha-hydroxylase defect.

Six healthy subjects were infused with angiotensin II and plasma concentrations of angiotensin, ACTH and cortisol were measured before, during and after the infusion. In all cases the plasma ACTH concentration fell as plasma angiotensin increased and rose again, sometimes to higher than basal levels, when the angiotensin infusion was terminated. These effects were most marked at the highest rate of infusion (8 pmol/kg/min) and, at the lower rates (2 and 4 pmol/kg/min), there was some recovery of ACTH levels during the infusion period in some subjects. Plasma ACTH concentrations also fell when angiotensin was infused into a patient with high ACTH levels due to a steroid 17 alpha-hydroxylation defect. The inhibition of ACTH secretion is not due to a rise in plasma cortisol operating a negative feedback inhibition. It could be a direct effect of the infused angiotensin on the brain-hypothalamus-pituitary complex or an effect on the metabolism of ACTH.

Adrenal Hyperplasia, Congenital↗