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Biomedical subjects

A F Lever

Publications and source records attributed to A F Lever.

At least 109 records · Page 6Linked to original sources
PubMed1984

Body elemental composition, with particular reference to total and exchangeable sodium and potassium and total chlorine, in untreated and treated primary hyperaldosteronism.

The whole body content of sodium, potassium, chlorine, calcium, phosphorus and nitrogen was measured by neutron activation analysis in 13 patients with untreated primary hyperaldosteronism (Conn's syndrome; aldosterone-secreting adenoma). Concurrently, exchangeable sodium and potassium were estimated by isotope dilution. Results were compared with values in the same patients during treatment with potassium-conserving diuretics and again after removal of the adenoma; and also with those in a series of 30 patients having untreated essential hypertension. Both total body and exchangeable sodium were high in Conn's syndrome before treatment and were reduced by spironolactone or amiloride and by subsequent surgery. There was no evidence of alteration in the proportion of non-exchangeable sodium in this disease, in contrast to earlier reports. Total body and exchangeable potassium were low in untreated Conn's syndrome and increased to normal after therapy: the proportion of non-exchangeable potassium was similar before and after treatment, and also similar to that in essential hypertension. Total body chlorine was increased before treatment in Conn's syndrome and returned to normal with therapy; body calcium, phosphorus and nitrogen were normal throughout.

Adult↗
PubMed1984

Changes in active and inactive renin and in angiotensin II across the kidney in essential hypertension and renal artery stenosis.

Investigations were performed in 26 patients with essential hypertension and 24 with unilateral renal artery stenosis. In each patient blood was drawn simultaneously and in triplicate, from both renal veins and aorta, for measurement of plasma concentrations of active and inactive renin and of angiotensin II. In 19 patients estimates of individual renal plasma flow were obtained in order to calculate secretion rates for active and inactive renin, and to assess the contribution of renin secretion rate and of renal plasma flow to the renal vein renin ratio. In patients with essential hypertension there was evidence that the kidney secreted active renin (18% mean increase in renal vein concentration above that of arterial plasma; P less than 0.001), but no evidence of secretion of inactive renin (4% mean increase; NS). There was a tendency for the kidney to extract angiotensin II (8% mean decrease in renal vein concentration below that of arterial plasma; P = 0.07). The affected kidney in patients with renal artery stenosis showed marked secretion of active renin (364% mean increase; P less than 0.001) and also secreted inactive renin (80% mean increase; P less than 0.05) with net generation of angiotensin II across the renal circulation (100% mean increase; P less than 0.05). The contralateral kidney exhibited suppressed secretion of active renin (3% mean increase; NS) with no evidence of secretion of inactive renin (2% mean increase; NS), and marked extraction of angiotensin II (50% mean decrease; P less than 0.001). The correlation between combined secretion rate of active renin by both kidneys and the arterial concentration of active renin in patients with essential and renovascular hypertension taken together was strongly positive (r = 0.82; P less than 0.01). The same correlation for inactive renin was weak (r = 0.32; NS). The correlation between the combined secretion rates of active renin by both kidneys and the circulating plasma concentration of angiotensin II (r = +0.60; P less than 0.05) was both significant and positive. By contrast, the total 'secretion' rate of angiotensin II by both kidneys was inversely related to arterial plasma angiotensin II (r = -0.92; P less than 0.001). This latter relationship suggests an important role for the kidney in clearing angiotensin II from the circulation, this being more marked the higher the arterial angiotensin II concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Relation of blood pressure and body sodium content during sodium depletion in normal and hypertensive subjects.

Blood pressure, exchangeable sodium content, sodium metabolic balance, and plasma concentrations of active renin, angiotensin II, and aldosterone were measured in seven normal men and 10 essential hypertensive men of similar age and weight. The measurements were made under two circumstances: during a 2- to 3-day period of normal sodium intake of 145-150 mmol/24 h and during a 2- to 3-day period of sodium depletion produced by 40 mg frusemide and a dietary sodium intake less than 10 mmol/24 h. Mean arterial pressure decreased in nine of the 10 hypertensive subjects but increased in six of the seven normotensive subjects during sodium depletion. Blood pressure changed more for a given change in exchangeable sodium level in hypertensive subjects than in normotensive subjects, despite a similar loss of sodium in the two groups. Changes in blood pressure varied markedly in the hypertensive group. Patients showing the greatest fall in arterial pressure had the least rise in plasma active renin concentration and, not significantly, the least rise in plasma aldosterone level. These findings are compatible with a model of pressure natriuresis which is altered more in normal subjects during changes in dietary sodium content, thereby preventing a rise in arterial pressure. Failure of this compensatory mechanism in hypertensive subjects may raise blood pressure.

Adult↗
PubMed1984

Pressor effects of brief and prolonged infusions of epinephrine in the conscious rat.

Plasma epinephrine may be increased in some patients with essential hypertension, and prolonged infusion of this catecholamine has been claimed to raise blood pressure. The objectives of our experiments were to determine whether continuous intravenous infusion of epinephrine raised blood pressure in a rat preparation known to respond in this way to angiotensin II in low dose and, if so, the plasma concentration of epinephrine required to raise pressure in comparison to the physiological range of plasma catecholamine concentration in the rat. Intravenous infusion of epinephrine at a rate of 400 ng X kg-1. min-1 or less for 30 min into Wistar rats did not increase mean arterial pressure (MAP); pressure did rise when the rate was increased to 800 ng X kg-1. min-1. However, when rats were given epinephrine at 400 ng X kg-1. min-1 for 4 days with continuous blood pressure recording, average MAP showed a progressive rise on successive days of infusion, reaching a maximum increase of 12 mmHg on the 4th and final day of infusion (P less than 0.02). Blood pressure did not change significantly during epinephrine infusion at 10 and 70 ng X kg-1. min-1. Plasma epinephrine was raised more than 13 times basal at the highest rate of infusion. In comparison, blood pressure and catecholamine concentrations increased only slightly although significantly during a period of restraint. We confirm the existence of a slowly developing pressor effect of epinephrine, but it is small and requires a large sustained increase of plasma epinephrine for its development.

Animals↗
PubMed1984

The effect of etomidate on adrenocortical function in dogs before and during hemorrhagic shock.

The effects of the hypnotic agent ethyl phenylethyl imidazole carboxylate (etomidate), on corticosteroidogenesis were studied in greyhound dogs during a 2-h period of anesthetic followed by a further 2 h of anesthetic combined with hemorrhage. Three groups of dogs were studied. The first, a control, received thiopentone and pentobartitone for induction and maintenance of anesthesia. A second control group received the chemically unrelated hypnotic preparation, althesin, after induction with thiopentone and pentobarbitone. In the first control group and the althesin-treated control group, changes in plasma ACTH and in plasma renin and angiotensin II concentrations were followed closely by changes in the levels of their respective dependent corticosteroids. A third experimental group received etomidate after induction of anesthesia with thiopentone and pentobarbitone. In these, in contrast, plasma levels of progesterone, 17 alpha-hydroxyprogesterone, corticosterone, cortisol, and aldosterone decreased during the experiment even failing to respond to massive rises in plasma ACTH concentration, renin, and angiotensin II levels after hemorrhage. However, the ability of 11-deoxycortisol and 11-deoxycorticosterone to respond was retained. These results suggest that etomidate inhibits corticosteroidogenesis directly, probably acting at more than one point in the biosynthetic pathway. It is suggested that it inhibits mitochondrial steroid hydroxylation (e.g. side chain cleavage, 11 beta-hydroxylation), but not 21-hydroxylation which occurs outside the mitochondrion.

Adrenal Cortex↗
PubMed1984

Enalapril in hypertension with renal artery stenosis: long-term follow-up and effects on renal function.

Enalapril alone, 10-40 mg given once-daily, controlled systemic hypertension long-term (mean follow-up time 19 months) in patients with renal artery stenosis. Significant, but usually modest, increases in serum creatinine and urea were observed. No serious side-effects were seen. A highly significant reduction in peripheral plasma angiotensin II was maintained 24 h after the previous dose of enalapril. Plasma active renin concentration rose 20-fold with long-term enalapril, when the stenotic kidney showed significant secretion of inactive, as well as of active renin. With enalapril therapy, the contralateral kidney showed net extraction of active renin. In unilateral renal artery stenosis, circulation on the affected side is diminished and is mainly via the juxtamedullary nephrons, which become rich in associated renin. Important intrarenal compensatory actions of the renin-angiotensin system include support of glomerular filtration, enhancement of vasa recta-mediated counter-current exchange, sustained urea excretion and maintenance of renal artery pressure distal to the stenosis. These compensatory effects are lost with converting enzyme inhibition. Thus in patients who are candidates for operation, enalapril should usually be given for no more than one month before proceeding to corrective surgery, to allow maximum blood pressure reduction without endangering the stenotic kidney for too long. Enalapril can nevertheless be given effectively long-term in patients unsuitable for corrective surgery.

Adolescent↗
PubMed1984

Body sodium blood volume state in essential hypertension: abnormal relation of exchangeable sodium to age and blood pressure in male patients.

The circulatory volume and exchangeable sodium (NaE) were measured by the Berne group in 110 normal subjects and 12 patients with benign untreated essential hypertension. Total plasma volume (PV) and blood volume (BV) correlated with total NaE (r = 0.64-0.75, p less than 0.001); these correlations were similar in normal and hypertensive subjects. PV, BV, and NaE related to body surface area averaged normal in the hypertensive population. PV and BV were unrelated to age or blood pressure in both normal and hypertensive subjects; NaE correlated positively with age (r = 0.25, p less than 0.02) and arterial pressure (r = 0.25, p less than 0.02) in essential hypertensive but not in normal subjects. These relationships in essential hypertension confirmed a previous observation by the Glasgow group. Moreover, a combined analysis of both study populations, with a total of 211 hypertensive patients, revealed significant correlations between NaE and age (r = 0.38, p less than 0.001) or arterial pressure (r = 0.40, p less than 0.001) in male but not in female subjects. The NaE was significantly decreased in hypertensive males less than 35 years old as compared with appropriate controls (95.8 +/- 5.1 vs 99.1 +/- 6.5%, p less than 0.02). BV and body sodium content are on average normal in patients with benign essential hypertension. The NaE may even be decreased in young male patients. These observations do not support the concept that body sodium and fluid volume expansion represent the initial event leading to high blood pressure in patients with essential hypertension.

Adolescent↗
PubMed1984

Renal secretion of inactive renin and extraction of angiotensin II in renal artery stenosis in man: factors determining renal vein renin ratio.

Triplicate blood samples were obtained, without stimulation, simultaneously from the aorta and both renal veins in 24 untreated hypertensive patients with unilateral renal artery stenosis. Across the affected kidney the plasma concentrations of active renin, inactive renin and angiotensin II increased by 363% (P less than 0.001), 80% (P less than 0.05) and 100% (P less than 0.05) respectively. Thus the affected kidney was secreting both active and inactive renin, while appreciable quantities of angiotensin II were generated across the renal circulation on that side. Across the contralateral unaffected kidney there were no significant changes in concentration of active or inactive renin, indicating net suppression of secretion of both forms of renin. Plasma angiotensin II concentration was however markedly reduced, to 50% of the arterial value (P less than 0.001), in the contralateral renal vein, demonstrating renal extraction of angiotensin II. In 14 patients renal plasma flow was also measured. The ratio of active renin concentration between the two renal veins correlated more closely with the renal plasma flow to the affected kidney (r = -0.81; P less than 0.01) than with renin secretion rate on that side (r = +0.37; NS). Thus reduction in renal blood flow rather than increase in renin secretion appeared to be the major determinant of renal vein renin ratio.

Angiotensin II↗
PubMed1984

Arterial blood pressure and plasma and body electrolytes in idiopathic hyperaldosteronism: a comparison with primary hyperaldosteronism (Conn's syndrome) and essential hypertension.

Exchangeable and plasma electrolytes, blood pressure and aldosterone were measured in groups of patients with idiopathic hyperaldosteronism, primary hyperaldosteronism and essential hypertension and in normal subjects. In idiopathic hyperaldosteronism exchangeable sodium was higher than in both essential hypertensive and normal groups but lower than in primary hyperaldosteronism. Plasma sodium results were similar except that no difference existed between the two forms of hyperaldosteronism. Plasma potassium concentration was lower in idiopathic hyperaldosteronism than in either essential hypertensive or in normal groups, but higher than in primary hyperaldosteronism. Blood pressure correlated with age in all groups and with exchangeable sodium in hypertensive patients. This was also the case with exchangeable sodium:exchangeable potassium ratio, but blood pressure did not correlate with aldosterone in any group. In idiopathic hyperaldosteronism, as in essential hypertension, sodium and blood pressure correlated strongly in male and weakly in female patients. The analysis reveals important differences between idiopathic and primary hyperaldosteronism and also between idiopathic hyperaldosteronism and essential hypertension.

Adult↗
PubMed1983

Enalapril in the treatment of hypertension with renal artery stenosis.

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in angiotensin I; this probably reflects the fall in renin substrate that occurs with converting enzyme inhibition. Enalapril alone caused reduction in exchangeable sodium, with distinct increases in serum potassium, creatinine, and urea. Enalapril was well tolerated and controlled hypertension effectively long term; only two of the 20 patients required concomitant diuretic treatment.

Adolescent↗
PubMed1983

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↗
PubMed1983

Inverse relation of exchangeable sodium and blood pressure in hypertensive patients with renal artery stenosis.

Measurements of exchangeable sodium, arterial pressure and plasma concentrations of active renin, angiotensin II, aldosterone, sodium and potassium were made in 35 hypertensive patients with renal artery stenosis, 30 having unilateral renal arterial lesions. Plasma urea was below 7 mmol/l in 24 of the patients with unilateral lesions. In these and in the whole group of 35 patients there were significant inverse correlations between exchangeable sodium and diastolic blood pressure and between plasma sodium concentration and diastolic pressure. Six patients had hyponatraemia with a plasma sodium concentration less than 135 mmol/l. All were sodium-deplete with secondary hyperaldosteronism, three also having malignant-phase hypertension. Twelve of the patients with unilateral renal artery stenosis underwent bilateral ureteric catheterization. Sodium excretion was greater from the contralateral kidney than from the affected kidney and the rate of sodium excretion from the former, but not from the latter, was significantly related to arterial pressure. The relation of diastolic blood pressure and exchangeable sodium is the opposite of the positive correlation found in essential hypertension and Conn's syndrome. In renal artery stenosis the inverse correlation could result from a natriuretic effect of increased arterial pressure occurring mainly in the contralateral kidney.

Adult↗
PubMed1983

Similar blood pressure but different outcome in rats with DOC and post-DOC hypertension.

It is uncertain whether increased arterial pressure alone or increased arterial pressure combined with some other factor is responsible for the development of malignant-phase hypertension. Our object was to test this comparing two groups of rats with hypertension of different mechanism but of similar duration and degree. Two experiments were done in hypertensive rats. In the first blood pressure was measured in the tail, in the second by intra-arterial catheter and pressure transducer. In the first, hypertension was produced in 30 male Sprague-Dawley rats by unilateral nephrectomy followed by thrice-weekly injections of deoxycorticosterone (12.5 mg) and substitution of 1% NaCl and 0.2% KCl for their drinking water. After four weeks 28 rats survived and systolic blood pressure had risen to 220 mmHg. The survivors were paired by blood pressure and randomly allocated either to continued DOC and salt or to a regime in which DOC was stopped and tap-water was substituted for the NaCl-KCl solution (post-DOC rats). Blood pressure remained similar in the two groups thereafter, but in every case it was the DOC-salt animal of the pair which died first. Fibrinoid arteriolar lesions of malignant-phase hypertension were significantly commoner in DOC-salt animals and, before death, they had more pronounced features of microangiopathic haemolytic anaemia. The second experiment was the same in design as the first except that two weeks after randomization the similarity of blood pressure was confirmed by measurement of intra-arterial pressure in eight pairs of DOC-salt and post-DOC rats. We conclude that increased arterial pressure is not the only factor influencing development of malignant-phase hypertension.

Animals↗
PubMed1983

New inhibitors of human renin tested in vitro and in vivo in the anaesthetized baboon.

A new inhibitor of human renin (H. 189) is described. It is a decapeptide analogue of human renin substrate with the amino acid, statine, substituted for leucine in the scissile bond. Its inhibitory potency as shown by IC50 is 1.0 X 10(-8) M with human plasma renin and 1.5 X 10(-8) M with baboon plasma renin. It is less effective with dog and rat renin, but its inhibitory potency with human renin is similar to that of another inhibitor of ours (H. 142) having a reduced isostere in the scissile bond. H. 189 has some inhibitory effect on cathepsin D (IC50 6.5 X 10(-5) M) but H. 142 has no discernible effect. Pepstatin, on the other hand, was highly effective against cathepsin D (IC50 1.2 X 10(-8) M). H. 142 and H. 189 were infused intravenously at 10 mg/kg/h in four anaesthetized salt-deplete baboons (Papio hamadryas). The activity of renin in plasma decreased markedly as did the circulating concentration of its products, angiotensin I and angiotensin II.

Anesthesia, General↗
PubMed1983

The renin-angiotensin system and total body sodium and potassium in hypertensive women taking oestrogen-progestagen oral contraceptives.

Measurements of total body sodium and potassium, and of components of the renin-angiotensin-aldosterone system, were made in a group of women who developed hypertension while taking oestrogen-progestagen oral contraceptives. The results were compared with similar measurements made in age-matched women with essential hypertension. Total body sodium and potassium were normal in both groups. Plasma renin-substrate was significantly elevated in the women taking oral contraceptives, while concentrations of active renin were similar and normal in both groups. Thus plasma angiotensin II was significantly elevated in the pill users; overall the product of renin and renin substrate concentrations correlated significantly with angiotensin II. The rise in plasma angiotensin II in conjunction with normal total body sodium could therefore contribute to the increase in blood pressure induced by oestrogen-progestagen oral contraceptives.

Adult↗
PubMed1983

Slow rise and diurnal change of blood pressure with saralasin and angiotensin II in rats.

Our objectives were to determine whether saralasin, like angiotensin II, raises blood pressure gradually when given by constant infusion and whether either agent alters the diurnal variation of arterial pressure. Eight female Wistar rats were infused intravenously with 5% dextrose for 2 days, then with saralasin at 10 micrograms . kg-1 . min-1 for 4 days, and finally with dextrose for 2 days. Six other rats were infused with angiotensin II (20 ng . kg-1 . min-1) instead of saralasin. Mean arterial pressure (MAP) was recorded continuously. Saralasin and angiotensin II gradually raised MAP in all rats, by 22.0 mmHg on the 4th day of saralasin and by 41.7 mmHg on the 4th day of angiotensin II. Both agents also increased the diurnal variation of blood pressure, MAP increasing 8.3-20.6 mmHg during the night and falling 6.7-19.1 mmHg during the day. Variability of arterial pressure was also increased by saralasin and in an earlier experiment by angiotensin II. We conclude that saralasin has a slow pressor action similar to that of angiotensin II but distinct in its timing both from the rapid agonist action of saralasin and from the acute vasoconstrictor action of angiotensin II. These effects of saralasin may compromise interpretation of experiments in which the drug is given by prolonged infusion to assess the role of angiotensin II.

Angiotensin II↗