Captopril in renovascular hypertension: long-term use in predicting surgical outcome.
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Captopril↗
Biomedical subjects
R Fraser
Publications and source records attributed to R Fraser.
Captopril in the management of hypertension with renal artery stenosis: its long-term effect as a predictor of surgical outcome.
Fifteen patients with hypertension and unilateral renal artery disease were treated with captopril alone; 10 came to operation and were later assessed postoperatively with no drug treatment. Captopril caused both immediate and sustained decreases in plasma angiotensin II and aldosterone, with increases in plasma active renin and blood angiotensin I concentrations. Decrements in systolic and diastolic pressure 2 hours after the first dose of captopril were closely correlated with the initial decreases in plasma angiotensin II. Blood pressure was decreased by long-term captopril therapy irrespective of whether plasma angiotensin II was abnormally high before treatment. The long-term response of both systolic and diastolic pressure correlated well with the response to surgery. By contrast, the blood pressure decrease 2 hours after the initial dose of captopril variously underestimated and overestimated the decrease during prolonged use of the drug and did not relate to surgical outcome. In patients who, before treatment, had secondary aldosteronism, hyponatremia, hypokalemia and sodium and potassium deficiency, captopril corrected these abnormalities. In the remaining patients, long-term captopril therapy did not alter exchangeable sodium, plasma sodium or total body potassium, although plasma potassium levels increased.
Adolescent↗
Captopril in renovascular hypertension: long-term use in predicting surgical outcome.
The angiotensin converting-enzyme inhibitor captopril was used as long-term preoperative treatment in a series of hypertensive patients with unilateral renal arterial disease. There were immediate and sustained falls in plasma angiotensin II and aldosterone concentrations, with converse increases in circulating renin and angiotensin I. In patients with sodium and potassium deficiency and secondary aldosterone excess before treatment captopril corrected the sodium and potassium deficits; in these cases the initial hypotensive response was profound but the later effect was less pronounced. When sodium and potassium state was initially normal it remained unchanged during captopril treatment, while the full hypotensive effect took up to three weeks to be attained. The immediate, but not long-term, falls in arterial pressure with captopril were proportional to the immediate decrements of plasma angiotensin II. Nevertheless, while the immediate blood-pressure reduction with captopril variously overestimated and underestimated the eventual surgical response, the absolute blood-pressure values during long-term captopril related well with those after operation. Pretreatment plasma renin and angiotensin II concentrations, while closely predicting the immediate captopril response, are fallible guides to surgical prognosis. In contrast, long-term treatment with converting-enzyme inhibitors may provide an accurate indication of surgical outcome.
Adolescent↗
Effect of changes in sodium balance on potassium/aldosterone dose-response curves in the dog.
1. Potassium was infused intravenously in an incremental fashion and the plasma aldosterone response were measured in conscious beagle dogs at five different intakes of dietary sodium. 2. Potassium/aldosterone dose-response curves were constructed for each dietary sodium regimen. 3. The rate of increase of plasma potassium during graded potassium infusion became progressively greater with increasing sodium depletion. 4. Regression lines of plasma aldosterone on plasma potassium were progressively elevated and steepened with increasing sodium depletion. 5. The alteration of these dose-response curves could in part have been the result of chronic elevation of plasma potassium and angiotensin II, and depression of plasma sodium, with sodium deprivation. 6. By contrast, acute changes in plasma angiotensin II or sodium concentrations across incremental infusions of potassium did not explain the progressive changes in the potassium/aldosterone dose-response curves. 7. The steepest part of the plasma aldosterone response curve was in the plasma potassium range 4-6 mmol/1. 8. Maximum achieved aldosterone levels were similar to or greater than those attained during angiotensin II infusion in previous studies in beagle dogs. 9. Potassium, like angiotensin II and adrenocorticotropic hormone, becomes a more effective stimulus to aldosterone with sodium depletion, thereby facilitating the preservation of sodium homoeostasis.
Aldosterone↗
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↗
Response of the renin-angiotensin-aldosterone system to upright tilting and to intravenous frusemide: effect of prior metoprolol and propranolol.
1 Upright tilting in normal volunteers caused increases in plasma active and total renin, angiotensin II and aldosterone; a slight but significant fall in inactive renin accompanied these changes. 2 The alterations in the renin-angiotensin-aldosterone system on tilting took up to 1 h upright to become fully established. 3 Large intravenous doses of propranolol or metoprolol attenuated, without abolishing, the rises in active renin, angiotensin II, and aldosterone; the attenuation was most evident soon after tilting and was largely overcome by 1 h upright. Inactive renin did not fall significantly after beta-adrenoceptor blockade. 4 Intravenous frusemide caused immediate rises in plasma active, total and inactive renin, angiotensin II, and aldosterone, which then declined over 2 h despite increasing cumulative sodium losses. 5 Intravenous propranolol or metoprolol attenuated, without abolishing, these early increases in the components of the renin-angiotensin-aldosterone system after frusemide. 6 Prior oral metoprolol or propranolol, while significantly slowing the heart, did not limit the early rise in plasma angiotensin II following intravenous frusemide. 7 Thus in contrast to previous workers, we did not find that propranolol eliminated the response of the renin-angiotensin system to upright tilting; in part this difference appeared to be due to the longer tilt we employed. 8 Also in contrast to earlier work, we found attenuation by both intravenous propranolol and metoprolol of the immediate rise in renin after intravenous frusemide.
Adrenergic beta-Antagonists↗
Captopril treatment: inter-dose variations in renin, angiotensins I and II, aldosterone and blood pressure.
1 The ability of captopril, 150 mg three times daily by mouth, to effect sustained reduction in plasma angiotensin II, with converse increases in circulating angiotensin I, and in active, inactive and total renin concentrations, has been assessed. 2 During prolonged treatment with captopril alone, and 12 h after the last dose of the drug, plasma angiotensin II remained approximately one-sixth of basal concentrations, while angiotensin I and renin concentrations were proportionately increased. However, further increases in angiotensin I, and in active, inactive and total renin concentrations, were seen 2 and 6 h after the morning dose of 150 mg captopril. 3 Inter-dose variations in plasma aldosterone and blood pressure were not closely related to concurrent variations in the renin-angiotensin system. 4 Arguments are presented for relying on measurements of plasma renin and angiotensin concentrations rather than of renin activity or aldosterone in assessing the effectiveness of converting enzyme inhibition.
Adolescent↗
Precocious pseudopuberty due to a rare form of congenital adrenal hyperplasia. Biochemical investigation and pitfalls in interpretation of hormone assays.
The biochemical investigation is described of a boy who presented with precocious puberty at the age of 3 years 9 months due to a rare form of congenital adrenal hyperplasia (CAH), steroid 11 beta-hydroxylase deficiency. Serum androgen levels were grossly elevated (17 hydroxyandrogens 10 nmol/l, androstenedione 129 nmol/l), 17 hydroxyprogesterone was modestly elevated (21 nmol/l), while serum gonadotrophins were low and testes were prepubertal in size. The major differential diagnosis was between an androgen-producing tumour and CAH. Initial serum and urine corticosteroid concentrations and their responses to dexamethasone were diagnostically misleading, later found to be due to lack of specificity of the radioimmunoassays and fluorimetric methods employed. Elevated basal plasma ACTH levels and suppression of androgen and ACTH levels by dexamethasone strongly suggested CAH. Definitive diagnosis of an 11 beta-hydroxylase defect was established by capillary column gas liquid chromatography of urine which demonstrated excess androgen and 11-deoxycortisol metabolites but no cortisol metabolites. The diagnosis was confirmed by specific serum assays of 11-deoxycortisol, deoxycorticosterone, and cortisol. The contribution of hormone assays and a protocol for their use in the diagnosis and monitoring of precocious puberty is discussed.
Adrenal Hyperplasia, Congenital↗
Effect of standard oral glucose loading on aldosterone secretion in primary hyperaldosteronism.
The effects of mild acute decreases in plasma potassium induced by standard oral glucose loading (100 g) on plasma aldosterone and renin levels were assessed in 10 patients with primary hyperaldosteronism as compared with 10 normal subjects. Following overnight fast, mean plasma glucose was identical in both groups; plasma insulin, potassium and renin levels were lower and plasma aldosterone higher in patients than in controls. Glucose loading significantly increased plasma glucose and insulin concentrations and decreased plasma potassium and aldosterone levels in both groups. The increases in plasma insulin and the decreases in plasma potassium or aldosterone tended to be blunted in primary hyperaldosteronism. glucose-induced changes in plasma aldosterone correlated significantly (P less than 0.025) with those in plasma potassium in the patients and with variations in plasma renin activity in the normal subjects. These findings suggest that the metabolic changes induced by glucose ingestion are capable of modifying aldosterone secretion in primary hyperaldosteronism. However, the glucose-induced decreases in plasma aldosterone are blunted in this disorder; this could be related to the impaired insulin response to glucose loading.
Adult↗
Effect of oral glucose loading on plasma insulin, potassium, renin and aldosterone in normal subjects and patients with primary hyperaldosteronism.
The effects of standard oral glucose loading (100 g) on plasma aldosterone and some regulatory factors were assessed in patients with primary hyperaldosteronism and normal subjects. Following overnight fast, mean plasma glucose was identical (10 patients and normal subjects approximately matched per age and sex); plasma insulin, potassium and renin levels were lower and plasma aldosterone higher in the patients. Glucose loading significantly increased plasma glucose and insulin concentrations and decreased plasma potassium and aldosterone levels in both groups; plasma renin activity was significantly increased only in normal subjects. The increases in plasma insulin and the decreases in plasma potassium or aldosterone tended to be blunted in primary hyperaldosteronism. Relationships among glucose-induced changes in plasma aldosterone and other factors were assessed by multiple regression analysis in these patients and normal subjects as well as an additional group of 21 normal subjects; in the latter, plasma cortisol was also measured and found to decrease significantly after glucose loading. Changes in plasma aldosterone correlated (P less than 0.025) more closely with those in plasma potassium in the patients and with variations in plasma renin activity in the normal subjects. These findings suggest that complex metabolic changes occur following glucose ingestion which are capable of modifying aldosterone secretion in normal subjects and primary hyperaldosteronism. The aldosterone-inhibitory effect of glucose tends to be blunted in the latter disorder. This could be related at least in part to an impaired insulin response in primary hyperaldosteronism.
Administration, Oral↗
Prolonged infusion of norepinephrine in the conscious dog: effects on blood pressure, heart rate, renin, angiotensin II, and aldosterone.
Eight conscious beagle dogs were given continuous intravenous infusions for 4 weeks: 0.9% NaCl solution was given for the first week; norepinephrine for the following 2 weeks, (at 125 ng/kg/min or at 250 ng/kg/min each in four dogs), 0.9% NaCl for the final week. Norepinephrine at the lower dose did not raise blood pressure but did reduce heart rate significantly. The higher rate of norepinephrine infusion raised blood pressure, but for the first week of infusion only, and again heart rate was reduced significantly during both weeks. Blood pressure fell on stopping infusion whether or not it had been raised previously. Plasma concentrations of renin, angiotensin II, and aldosterone were reduced, but the changes were of borderline significance only. These changes occurred when plasma concentrations of norepinephrine were increased four-sevenfold. The acute response to high infusion rates of norepinephrine (500, 1,000, and 2,000 ng/kg/min each for 1 h) was tested at weekly intervals in each dog. At each of these high rates of infusion, blood pressure, renin and angiotensin II, and haematocrit increased while plasma potassium concentration and heart rate fell. These changes occurred with increases of plasma norepinephrine greater than 14-fold. Prolonged infusion of norepinephrine did not alter the relation between plasma norepinephrine and arterial pressure as assessed by these dose-response studies.
Aldosterone↗
Sodium and potassium in essential hypertension.
A study was carried out of arterial pressure and body content of electrolytes in 91 patients with essential hypertension and 121 normal controls. Exchangeable sodium was found to be positively correlated with arterial pressure in the patients, the correlation being closest in older patients; values of exchangeable sodium were subnormal in young patients; and plasma, exchangeable, and total body potassium correlated inversely with arterial pressure in the patients, the correlations being closest in young patients. Three hypotheses were proposed to explain the mechanisms relating electrolytes and arterial pressure in essential hypertension--namely, a cell-salt hypothesis, a dietary salt hypothesis, and a kidney-salt hypothesis. It was concluded that two mechanisms probably operate in essential hypertension. In the early stages of the disease blood pressure is raised by an abnormal process related more closely to potassium than to sodium. A renal lesion develops later, possibly as a consequence of the hypertension. This lesion is characterised by resetting of pressure natriuresis and is manifest by an abnormal relation between body sodium and arterial pressure and by susceptibility to increased dietary sodium intake.
Adult↗
The myth of idiopathic hyperaldosteronism.
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Adenoma↗
The wound fibroblast and macrophage. I: Wound cell population changes observed in tissue culture.
The number and type of cells which migrated from sequential explants of wounded fascia in rats reflected the dense and changing cell populations observed in healing wounds. Macrophages appeared in large numbers from explants taken in the 5 days following injury, thereafter fibroblast-like cells predominated. The results support the hypothesis that the fibroblast-like cell of tissue culture is the same as the wound fibroblast. The technique can be used to obtain wound cells and provides a useful bridge between in vivo and in vitro means of investigating wound repair.
Animals↗
Transplantation antigen expression on murine trophoblast detection by induction of specific alloimmunity.
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Animals↗
Circulating dopamine: its effect on the plasma concentrations of catecholamines, renin, angiotensin, aldosterone and vasopressin in the conscious dog.
1. Six male beagle dogs with carotid loops were infused with sodium chloride solution (150 mmol/l; saline) during control observations followed by dopamine infusion at various rates. Arterial blood samples were drawn during the control period and at the end of each period of dopamine infusion for the measurement of plasma dopamine, noradrenaline, adrenaline, renin, angiotensin II, aldosterone, vasopressin, electrolytes and packed cell volume. Blood pressure and pulse were recorded throughout. 2. The rate of infusion and plasma dopamine levels were closely correlated (r = 0.99, P less than 0.001). Plasma dopamine levels two to 20 times basal values produced no significant change in any of the other variables measured; levels 200 times basal values caused a significant increase (P less than 0.05) in plasma renin concentration; levels 2000 times basal values were associated with significant increases (P less than 0.05) in plasma renin and angiotensin II, packed cell volume and blood pressure, without significant changes in other measurements. 3. Circulating dopamine is unlikely to be important in the control of sodium and water metabolism.
Aldosterone↗
Relation of arterial pressure with exchangeable and total body sodium and with plasma exchangeable and total body potassium in essential hypertension.
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Adult↗